Neuronal migration disorder (NMD) refers to a heterogenous group of disorders that, it is supposed, share the same etiopathological mechanism: a variable degree of disruption in the migration of neuroblasts during neurogenesis. The neuronal migration disorders are termed cerebral dysgenesis disorders, brain malformations caused by primary alterations during neurogenesis; on the other hand, brain malformations are highly diverse and refer to any insult to the brain during its formation and maturation due to intrinsic or extrinsic causes that ultimately will alter the normal brain anatomy. However, there is some controversy in the terminology because virtually any malformation will involve neuroblast migration, either primarily or secondarily.

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Wiki: Abnormality of neuronal migration

    Acrocallosal syndrome (also known as ACLS) is an extremely rare autosomal recessive syndrome characterized by corpus callosum agenesis, polydactyly, multiple dysmorphic features, motor and intellectual disabilities, and other symptoms. The syndrome was first described by Albert Schinzel in 1979. Mutations in KIF7 are causative for ACLS, and mutations in GLI3 are associated with a similar syndrome.

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Wiki: Acrocallosal syndrome

    Adrenoleukodystrophy (ALD) is a disease linked to the X chromosome. It is a result of fatty acid buildup caused by failure of peroxisomal fatty acid beta oxidation which results in the accumulation of very long chain fatty acids in tissues throughout the body. The most severely affected tissues are the myelin in the central nervous system, the adrenal cortex, and the Leydig cells in the testes. The long chain fatty acid buildup causes damage to the myelin sheath of the neurons of the brain, resulting in seizures and hyperactivity. Other symptoms include problems in speaking, listening, and understanding verbal instructions. Clinically, ALD presents as a heterogeneous disorder, showing several distinct phenotypes, and no clear pattern of genotype¨Cphenotype correlation. As an X-linked disorder, ALD presents most commonly in males; however, approximately 50% of heterozygote females show some symptoms later in life. Approximately two-thirds of ALD patients will present with the childhood cerebral form of the disease, which is the most severe form. It is characterized by normal development in early childhood, followed by rapid degeneration to a vegetative state. The other forms of ALD vary in timing of onset and in clinical severity, ranging from adrenal insufficiency alone to progressive paraparesis in early adulthood. ALD is caused by mutations in ABCD1, a gene located on the X chromosome that codes for ALD, a peroxisomal membrane transporter protein. The exact mechanism of the pathogenesis of the various forms of ALD is not known. Biochemically, individuals with ALD show very high levels of unbranched, saturated, very long chain fatty acids, particularly cerotic acid (26:0). The level of cerotic acid in plasma does not correlate with clinical presentation. Treatment options for ALD are limited. For the childhood cerebral form, stem cell transplant and gene therapy are options if the disease is detected early in the clinical course. Adrenal insufficiency in ALD patients can be successfully treated. ALD is the most common peroxisomal inborn error of metabolism, with an incidence estimated between 1:18,000 and 1:50,000. It does not have a significantly higher incidence in any specific ethnic group.

Reference
Wiki: Adrenoleukodystrophy

    Andermann syndrome, also known as agenesis of corpus callosum with neuronopathy (ACCPN), Charlevoix disease and KCC3 axonopathy among other names, is a very rare neurodegenerative genetic disorder that damages the nerves used to control muscles and related to sensation and is often associated with agenesis of the corpus callosum. It was first described in 1972 by Frederick and Eva Andermann et al.

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Wiki: Agenesis of the corpus callosum with peripheral neuropathy

    A syndrome characterized by arthrogryposis, cerebral parenchymal underdevelopment, clubfoot, and global developmental delay with severe cases being incompatible with life that has_material_basis_in homozygous or compound heterozygous mutation in the KIAA1109 gene on chromosome 4q27.

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DiseaseOntology: Alkuraya-kucinskas syndrome

    An alpha thalassemia that has_material_basis_in mutation in the ATRX gene on Xq21.

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DiseaseOntology: Alpha thalassemia-x-linked intellectual disability syndrome

    A syndrome that is characterized by delayed development, intellectual disability, severe speech impairment, and problems with movement and balance.

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DiseaseOntology: Angelman syndrome

    An eating disorder characterized by refusal to maintain a healthy body weight, and an obsessive fear of gaining weight due to a distorted self image.

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DiseaseOntology: Anorexia nervosa

    Tauopathies are a class of neurodegenerative diseases characterized by the aggregation of abnormal tau protein.[1] Hyperphosphorylation of tau proteins causes them to dissociate from microtubules and form insoluble aggregates called neurofibrillary tangles.[2] Various neuropathologic phenotypes have been described based on the anatomical regions and cell types involved as well as the unique tau isoforms making up these deposits. The designation 'primary tauopathy' is assigned to disorders where the predominant feature is the deposition of tau protein. Alternatively, diseases exhibiting tau pathologies attributed to different and varied underlying causes are termed 'secondary tauopathies'. Some neuropathologic phenotypes involving tau protein is Alzheimer's disease, Pick disease, Progressive supranuclear palsy, and corticobasal degeneration.[1]

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Wiki: Argyrophilic grain disease

    Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by executive dysfunction occasioning symptoms of inattention, hyperactivity, impulsivity and emotional dysregulation that are excessive and pervasive, impairing in multiple contexts, and otherwise age-inappropriate.[8]

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Wiki: Attention-deficit/hyperactivity disorder

    Cerebral palsy (CP) is defined as a nonprogressive but not unchanging disorder of posture or movement, caused by an abnormality of the brain and first evident at the stage of rapid brain development (Hughes and Newton, 1992). It is a common disorder of childhood, with an incidence of 1 in 250 to 1,000 births (Pharoah et al., 1987; Bundey and Alam, 1993). Ataxic cerebral palsy accounts for 5 to 10% of all forms of CP, and approximately 50% of ataxic CP is thought to be inherited as an autosomal recessive trait (McHale et al., 2000). Also see spastic cerebral palsy (e.g., 612900).

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OMIM: Atypical cerebral palsy

    Okamoto syndrome (OS), also known as Au¨CKline syndrome (AKS), is a very rare autosomal dominant genetic condition characterised by congenital hydronephrosis, low muscle tone, heart defects, intellectual disability and characteristic facial features.[4][6] Those affected often have neurological and skeletal abnormalities, as well as frequent urinary tract infections. Language and walking are usually delayed. Facial features include prominent, downturned ears, an open, downturned mouth and drooping eyelids (ptosis).[4][5]

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Wiki: Au-Kline syndrome

    Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006).

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OMIM: Autism syndrome

    Classic autism, also known as childhood autism, autistic disorder, (early) infantile autism, infantile psychosis, Kanner's autism, Kanner's syndrome, or (formerly) just autism, is a neurodevelopmental condition first described by Leo Kanner in 1943. It is characterized by atypical and impaired development in social interaction and communication as well as restricted, repetitive behaviors, activities, and interests. These symptoms first appear in early childhood and persist throughout life. It was last recognized as a diagnosis in the DSM-IV and ICD-10, and has been superseded by autism spectrum disorder in the DSM-5 (2013) and ICD-11 (2022). Globally, classic autism was estimated to affect 24.8 million people as of 2015. Autism is caused by a combination of genetic and environmental factors, with genetic factors thought to heavily predominate. Controversies surrounded other proposed environmental causes; for example, the vaccine hypothesis, which although disproved, continues to hold sway in certain communities. After DSM-5/ICD-11 the term "autism" has become more commonly used in reference to the autism spectrum more broadly.

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Wiki: Autistic disorder

    Autosomal recessive axonal neuropathy with neuromyotonia, also known as Gamstorp-Wohlfart syndrome, is a rare hereditary disorder which is characterized by progressive poly-neuropathy, neuromyotonia, myokymia, pseudo-myotonia, hand-foot contractures, and abnormal neuro-myotonic/myokimic activity visible on needle EMG. According to OMIM, around 52 cases have been reported in medical literature However; new cases (mostly from Europe and North America) have been reported since 2014.

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Wiki: Autosomal recessive axonal neuropathy with neuromyotonia

    Ichthyosis-intellectual disability-dwarfism-renal impairment is a very rare autosomal recessive ichthyotic genetic disorder which consists of congenital ichthyosis, intellectual disabilities, dwarfism/short stature and renal impairment. This condition has been described only in four members of an Iranian family and was discovered in the summer of 1975.

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Wiki: Autosomal recessive intellectual disability

    Gray matter heterotopia is a neurological disorder caused by gray matter being located in an atypical location in the brain. Grey matter heterotopia is characterized as a type of focal cortical dysplasia. The neurons in heterotopia are otherwise healthy; nuclear studies have shown glucose metabolism equal to that of normally positioned gray matter. The condition causes a variety of symptoms, but usually includes some degree of epilepsy or recurring seizures, and often affects the brain's ability to function. Symptoms vary in severity; the condition is occasionally discovered as an incidentaloma when brain imaging performed for an unrelated problem and has no apparent ill effect on the patient. In other cases, heterotopia can result in severe seizure disorders, loss of motor skills, and intellectual disability.

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Wiki: Band heterotopia

    A syndrome characterized by distinctive facial features including hypertelorism, large eyelid openings, ptosis, high-arched eyebrows, a broad nasal bridge and tip of the nose, a long space between the nose and the upper lip, full cheeks and a pointed chin; structural abnormalities of the brain might also be present.

Reference
DiseaseOntology: Baraitser-Winter syndrome

    Primary familial brain calcification (PFBC), also known as familial idiopathic basal ganglia calcification (FIBGC) and Fahr's disease, is a rare, genetically dominant or recessive, inherited neurological disorder characterized by abnormal deposits of calcium in areas of the brain that control movement. Through the use of CT scans, calcifications are seen primarily in the basal ganglia and in other areas such as the cerebral cortex.

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Wiki: Basal ganglia calcification

    A syndromic X-linked intellectual disability characterized by global developmental delay apparent from infancy, feeding difficulties, hypotonia, and poor or absent speech that has_material_basis_in hemizygous or heterozygous mutation in the MSL3 gene on chromosome Xp22.2.

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DiseaseOntology: Basilicata-Akhtar syndrome

    Batten disease is a fatal disease of the nervous system that typically begins in childhood.[1] Onset of symptoms is usually between 5 and 10 years of age.[1] Often, it is autosomal recessive. It is the common name for a group of disorders called the neuronal ceroid lipofuscinoses (NCLs).[1]

Reference
Wiki: Batten disease

    Behr syndrome is characterized by the association of early-onset optic atrophy with spinocerebellar degeneration resulting in ataxia, pyramidal signs, peripheral neuropathy and developmental delay. Although it is an autosomal recessive disorder, heterozygotes may still manifest much attenuated symptoms. Autosomal dominant inheritance also being reported in a family. Recently a variant of OPA1 mutation with phenotypic presentation like Behr syndrome is also described. Some reported cases have been found to carry mutations in the OPA1, OPA3 or C12ORF65 genes which are known causes of pure optic atrophy or optic atrophy complicated by movement disorder.

Reference
Wiki: Behr syndrome

    Biotin-thiamine-responsive basal ganglia disease (BTBGD) is a rare disease that affects the nervous system, particularly the basal ganglia in the brain. It is a treatable neurometabolic disorder with autosomal recessive inheritance. First described in 1998 and then genetically distinguished in 2005, the disease is characterized by progressive brain damage that, if left untreated, can lead to coma and/or death. Commonly observed in individuals with BTBGD is recurring subacute encephalopathy along with confusion, seizures, and disordered movement (hypokinesia). BTBGD has several alternate names, including: BTRBGD Biotin-responsive basal ganglia disease (BBGD) Thiamine metabolism dysfunction syndrome 2 (biotin or thiamine-responsive type) (THMD2) Thiamine-responsive encephalopathy Thiamine transporter-2 deficiency

Reference
Wiki: Biotin-responsive basal ganglia disease

    Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that each last from days to weeks. If the elevated mood is severe or associated with psychosis, it is called mania; if it is less severe and does not significantly affect functioning, it is called hypomania. During mania, an individual behaves or feels abnormally energetic, happy or irritable, and they often make impulsive decisions with little regard for the consequences. There is usually also a reduced need for sleep during manic phases. During periods of depression, the individual may experience crying and have a negative outlook on life and poor eye contact with others. The risk of suicide is high; over a period of 20 years, 6% of those with bipolar disorder died by suicide, while 30¨C40% engaged in self-harm. Other mental health issues, such as anxiety disorders and substance use disorders, are commonly associated with bipolar disorder. While the causes of this mood disorder are not clearly understood, both genetic and environmental factors are thought to play a role. Many genes, each with small effects, may contribute to the development of the disorder. Genetic factors account for about 70¨C90% of the risk of developing bipolar disorder. Environmental risk factors include a history of childhood abuse and long-term stress. The condition is classified as bipolar I disorder if there has been at least one manic episode, with or without depressive episodes, and as bipolar II disorder if there has been at least one hypomanic episode (but no full manic episodes) and one major depressive episode. It is classified as cyclothymia if there are hypomanic episodes with periods of depression that do not meet the criteria for major depressive episodes. If these symptoms are due to drugs or medical problems, they are not diagnosed as bipolar disorder. Other conditions that have overlapping symptoms with bipolar disorder include attention deficit hyperactivity disorder, personality disorders, schizophrenia, and substance use disorder as well as many other medical conditions. Medical testing is not required for a diagnosis, though blood tests or medical imaging can rule out other problems. Mood stabilizers¡ªlithium and certain anticonvulsants such as valproate and carbamazepine as well as atypical antipsychotics such as aripiprazole¡ªare the mainstay of long-term pharmacologic relapse prevention. Antipsychotics are additionally given during acute manic episodes as well as in cases where mood stabilizers are poorly tolerated or ineffective. In patients where compliance is of concern, long-acting injectable formulations are available. There is some evidence that psychotherapy improves the course of this disorder. The use of antidepressants in depressive episodes is controversial: they can be effective but have been implicated in triggering manic episodes. The treatment of depressive episodes, therefore, is often difficult. Electroconvulsive therapy (ECT) is effective in acute manic and depressive episodes, especially with psychosis or catatonia. Admission to a psychiatric hospital may be required if a person is a risk to themselves or others; involuntary treatment is sometimes necessary if the affected person refuses treatment. Bipolar disorder occurs in approximately 2% of the global population. In the United States, about 3% are estimated to be affected at some point in their life; rates appear to be similar in females and males. Symptoms most commonly begin between the ages of 20 and 25 years old; an earlier onset in life is associated with a worse prognosis. Interest in functioning in the assessment of patients with bipolar disorder is growing, with an emphasis on specific domains such as work, education, social life, family, and cognition. Around one-quarter to one-third of people with bipolar disorder have financial, social or work-related problems due to the illness. Bipolar disorder is among the top 20 causes of disability worldwide and leads to substantial costs for society. Due to lifestyle choices and the side effects of medications, the risk of death from natural causes such as coronary heart disease in people with bipolar disorder is twice that of the general population.

Reference
Wiki: Bipolar disorder

    An X-linked disease that is characterized by intellectual disability, truncal obesity, seizures, hypogonadism, developmental delay, distinctive facial features, tapered fingers and short toes and has_material_basis_in X-linked recessive inheritance of mutations in the PHF6 gene.

Reference
DiseaseOntology: Boerjeson-Forssman-Lehmann syndrome

    An X-linked disease that is characterized by intellectual disability, truncal obesity, seizures, hypogonadism, developmental delay, distinctive facial features, tapered fingers and short toes and has_material_basis_in X-linked recessive inheritance of mutations in the PHF6 gene.

Reference
DiseaseOntology: Borjeson-forssman-lehmann syndrome

    A glioma is a type of tumor that starts in the glial cells of the brain or the spine.[2] Gliomas comprise about 30 percent of all brain tumors and central nervous system tumours, and 80 percent of all malignant brain tumours.[3]

Reference
Wiki: Brain lower grade glioma

    A syndrome that is characterized by delayed psychomotor development, intellectual disability, truncal hypotonia, spasticity, and peripheral neuropathy and that has_material_basis_in heterozygous mutation in the ATAD3A gene on chromosome 1p36.

Reference
DiseaseOntology: Buratti-Harel syndrome

    Carpal tunnel syndrome (CTS) is the collection of symptoms and signs associated with nerve compression of the median nerve at the carpal tunnel. Most CTS is related to idiopathic compression of the median nerve as it travels through the wrist at the carpal tunnel (IMNCT). Idiopathic means that there is no other disease process contributing to pressure on the nerve. As with most structural issues, it occurs in both hands, and the strongest risk factor is genetics. Other conditions can cause CTS such as wrist fracture or rheumatoid arthritis. After fracture, swelling, bleeding, and deformity compress the median nerve. With rheumatoid arthritis, the enlarged synovial lining of the tendons causes compression. The main symptoms are numbness and tingling in the thumb, index finger, middle finger and the thumb side of the ring finger. People often report pain, but pain without tingling is not characteristic of IMNCT. Rather, the numbness can be so intense that it is described as painful. Symptoms are typically most troublesome at night. Many people sleep with their wrists bent, and the ensuing symptoms may lead to awakening. Untreated, and over years to decades, IMNCT causes loss of sensibility and weakness and shrinkage (atrophy) of the muscles at the base of the thumb. Work-related factors such as vibration, wrist extension or flexion, hand force, and repetition are proposed risk factors for IMNCT. But to date, there is mostly evidence of association with symptoms (CTS), not neuropathy (IMNCT), which is an important distinction. The only certain risk factor for IMNCT is genetics. All other risk factors are open to debate. It is important to consider IMNCT separately from CTS in diseases such as rheumatoid arthritis. Diagnosis of IMNCT can be made with a high probability based on characteristic symptoms and signs. IMNCT can be measured with electrodiagnostic tests. People wake less often at night if they wear a wrist splint. Injection of corticosteroids may or may not alleviate better than simulated (placebo) injections. There is no evidence that corticosteroid injection sustainably alters the natural history of the disease, which seems to be a gradual progression of neuropathy. Surgery to cut the transverse carpal ligament is the only known disease modifying treatment.

Reference
Wiki: Carpal tunnel syndrome

    A syndrome that has_material_basis_in homozygous mutation in the SNAP29 gene and characterized by a unique constellation of clinical manifestations including microcephaly, severe neurologic impairment, psychomotor retardation, failure to thrive, facial dysmoprhism, palmoplantar keratoderma and late-onset ichthyosis.

Reference
DiseaseOntology: Cednik syndrome

    Cephalocera is a genus of flies in the family Mydidae.

Reference
Wiki: Cephalocele

    An amyloidosis where amyloid protein progressively deposits in cerebral blood vessel walls with subsequent degenerative vascular changes that usually result in spontaneous cerebral hemorrhage, ischemic lesions and progressive dementia.

Reference
DiseaseOntology: cerebral amyloid angiopathy

    An amino acid metabolic disorder that is characterized by mental retardation, severe speech delay, behavioral abnormalities and seizures, has_material_basis_in mutation in the creatine transporter gene on chromosome Xq28.

Reference
DiseaseOntology: Cerebral creatine deficiency syndrome

    Neuronal ceroid lipofuscinosis is the general name for a family of at least eight genetically separate neurodegenerative lysosomal storage diseases that result from excessive accumulation of lipopigments (lipofuscin) in the body's tissues. These lipopigments are made up of fats and proteins. Their name comes from the word stem "lipo-", which is a variation on lipid, and from the term "pigment", used because the substances take on a greenish-yellow color when viewed under an ultraviolet light microscope. These lipofuscin materials build up in neuronal cells and many organs, including the liver, spleen, myocardium, and kidneys.

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Wiki: Ceroid lipofuscinosis neuronal

    Charcot¨CMarie¨CTooth disease (CMT) is a hereditary motor and sensory neuropathy of the peripheral nervous system characterized by progressive loss of muscle tissue and touch sensation across various parts of the body. This disease is the most commonly inherited neurological disorder, affecting about one in 2,500 people. It is named after those who classically described it: the Frenchman Jean-Martin Charcot (1825¨C1893), his pupil Pierre Marie (1853¨C1940), and the Briton Howard Henry Tooth (1856¨C1925). There is no known cure. Care focuses on maintaining function. CMT was previously classified as a subtype of muscular dystrophy.

Reference
Wiki: Charcot-Marie-Tooth disease

    Absence seizures are one of several kinds of generalized seizures. In the past, absence epilepsy was referred to as "pyknolepsy," a term derived from the Greek word "pyknos," signifying "extremely frequent" or "grouped". These seizures are sometimes referred to as petit mal seizures (from the French for "little illness", a term dated to the late 18th century); however, usage of this terminology is no longer recommended. Absence seizures are characterized by a brief loss and return of consciousness, generally not followed by a period of lethargy (i.e. without a notable postictal state). Absence seizures are most common in children. They affect both sides of the brain. Childhood absence epilepsy represents a significant portion, accounting for approximately 10 to 17%, of all cases of childhood-onset epilepsy, establishing it as the most common form of pediatric epilepsy. This syndrome is characterized by daily occurrences of frequent but brief episodes of staring spells. These episodes typically commence between the ages of 4 to 8 years and manifest in otherwise seemingly healthy children. On classic electroencephalograms (EEGs), distinct patterns emerge, featuring generalized spike-wave bursts occurring at a frequency of 3 Hz, accompanied by normal background brain activity. Despite sometimes being mistakenly perceived as a benign type of epilepsy, childhood absence epilepsy is associated with varying rates of remission. Children affected by this condition often experience cognitive deficits and encounter enduring psychosocial challenges in the long term.

Reference
Wiki: Childhood absence epilepsy

    A neurodegenerative disease characterized by loss of motor and cognitive skills between ages 2 and 7 years with progressive cerebral and cerebellar atrophy, resulting in the inability to walk, absence of language, and profound intellectual disability, that has_material_basis_in heterozygous mutation in the UBTF gene on chromosome 17q21.31.

Reference
DiseaseOntology: childhood-onset neurodegeneration with brain atrophy

    Chorea-acanthocytosis (ChAc, also called choreoacanthocytosis) is a rare hereditary disease caused by a mutation in a gene that directs structural proteins in red blood cells. It belongs to a group of four diseases characterized under the name neuroacanthocytosis. When a patient's blood is viewed under a microscope, some of the red blood cells appear thorny. These thorny cells are called acanthocytes. Other effects of the disease may include epilepsy, behaviour changes, muscle degeneration, and neuronal degradation similar to Huntington's disease. The average age of onset of symptoms is 35 years. The disease is incurable and inevitably leads to premature death. Chorea-acanthocytosis is a very complex autosomal recessive adult-onset neurodegenerative disorder. It often shows itself as a mixed movement disorder, in which chorea, tics, dystonia and even parkinsonism may appear as a symptom. This disease is also characterized by the presence of a few different movement disorders including chorea, dystonia etc. Chorea-acanthocytosis is considered an autosomal recessive disorder, although a few cases with autosomal dominant inheritance have been noted.

Reference
Wiki: Choreoacanthocytosis

    Christianson syndrome is an X linked syndrome associated with intellectual disability, microcephaly, seizures, ataxia and absent speech.

Reference
Wiki: Christianson syndrome

    Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repeated trauma to the head. The encephalopathy symptoms can include behavioral problems, mood problems, and problems with thinking. The disease often gets worse over time and can result in dementia. Most documented cases have occurred in athletes involved in striking-based combat sports, such as boxing, kickboxing, mixed martial arts, and Muay Thai¡ªhence its original name dementia pugilistica (Latin for "boxer's dementia")¡ªand contact sports such as American football, Rugby league, Rugby union, Australian rules football, professional wrestling, and ice hockey. It is also an issue in cheerleading, as well as association football (soccer), but largely as a result of "heading" the ball rather than player contact. Other risk factors include being in the military (combat arms), prior domestic violence, and repeated banging of the head. The exact amount of trauma required for the condition to occur is unknown, and as of 2022 definitive diagnosis can only occur at autopsy. The disease is classified as a tauopathy. There is no specific treatment for the disease. Rates of CTE have been found to be about 30% among those with a history of multiple head injuries; however, population rates are unclear. Research in brain damage as a result of repeated head injuries began in the 1920s, at which time the condition was known as dementia pugilistica or "boxer's dementia", "boxer's madness", or "punch drunk syndrome". It has been proposed that the rules of some sports be changed as a means of prevention.

Reference
Wiki: Chronic traumatic encephalopathy

    An autosomal dominant intellectual developmental disorder that has_material_basis_in heterozygous mutation in the TRIP12 gene on chromosome 2q36.

Reference
DiseaseOntology: Clark-Baraitser syndrome

    A neuromuscular junction disease that is characterized by weakness and easy fatiguability resulting from a genetic defect at the junction where the nerve stimulates muscle activity that result in muscle weakness and may affect nerve cells (presynaptic), muscle cells (postsynaptic) or the space between nerve and muscle cells (synaptic).

Reference
DiseaseOntology: Congenital myasthenic syndrome

    Focal cortical dysplasia (FCD) is a congenital abnormality of brain development where the neurons in an area of the brain failed to migrate in the proper formation in utero. Focal means that it is limited to a focal zone in any lobe. Focal cortical dysplasia is a common cause of intractable epilepsy in children and is a frequent cause of epilepsy in adults. There are three types of FCD with subtypes, including type 1a, 1b, 1c, 2a, 2b, 3a, 3b, 3c, and 3d, each with distinct histopathological features. All forms of focal cortical dysplasia lead to disorganization of the normal structure of the cerebral cortex : Type 1 FCD exhibits subtle alterations in cortical lamination. Type 2a FCD exhibits neurons that are larger than normal that are called dysmorphic neurons (DN). FCD type 2b exhibits complete loss of laminar structure, and the presence of DN and enlarged cells are called balloon cells (BC) for their large elliptical cell body shape, laterally displaced nucleus, and lack of dendrites or axons. The developmental origin of balloon cells is currently believed to be derived from neuronal or glial progenitor cells. Balloon cells are similar in structure to giant cells in the disorder tuberous sclerosis complex. Type 3 FCDs are cortical disorganisation associated with other lesions such as hippocampal sclerosis (type 3a), long-term epilepsy-associated tumors (3b), vascular malformations (3c) or scar/hypoxic damages (3d). Recent studies have demonstrated that FCD types 2a and 2b result from somatic mutations in genes that encode components of the mammalian target of rapamycin (mTOR) pathway. Causative gene mutations for types 1 and 3 have not been identified. The mTOR pathway regulates a number of functions in the brain including establishment of cell size, cell motility, and differentiation. Gene mutations associated with FCD2a and FCD 2b include MTOR, PI3KCA, AKT3, and DEPDC5. Mutations in these genes lead to enhanced mTOR pathway signaling at critical periods in brain development. Some recent evidence may suggest a role for in utero infection with certain viruses such as cytomegalovirus and human papilloma virus. Seizures in FCD are likely caused by abnormal circuitry induced by the presence of DNs and BCs. These abnormal cell types generate abnormal electrical signals which spread out to affect other parts of the cerebral cortex. Medication is used to treat the seizures that may arise due to cortical dysplasia. Epilepsy surgery to remove areas of FCD is a viable treatment option for appropriate candidates.

Reference
Wiki: Cortical dysplasia

    Dejerine¨CSottas disease, also known as, Dejerine¨CSottas syndrome,[3] hereditary motor and sensory polyneuropathy type III, and Charcot¨CMarie¨CTooth disease type 3, is a hereditary neurological disorder characterized by damage to the peripheral nerves, demyelination, and resulting progressive muscle wasting and somatosensory loss. The condition is caused by mutations in various genes and currently has no known cure.[2]

Reference
Wiki: Dejerine-Sottas syndrome

    A language delay is a language disorder in which a child fails to develop language abilities at the usual age-appropriate period in their developmental timetable. It is most commonly seen in children ages two to seven years-old and can continue into adulthood. The reported prevalence of language delay ranges from 2.3 to 19 percent. Language is a uniquely human form of communication that entails the use of words in a standard and structured way. Language is distinct from communication. Communication is a two-stage process. The first stage is the process of encoding the message into a set of words (or signs in the case of Sign Languages) and sentence structures that convey the required meaning, i.e. into language. In the second stage, language is translated into motor commands that control the articulators (hands, face, body, lungs, vocal cords, mouth, tongue, teeth, etc.), thereby creating speech. Language delays are distinct from speech delays, in which the development of the mechanical and motor aspects of speech production are delayed. Many tend to confuse language delay with speech delay or even just late talker. All of these have different telltale signs and determining factors. Speech delay seems to be more similar to late talker compared to language delay. Speech is the verbal motor production of language, while language is a means of communication. Because language and speech are independent, they may be individually delayed. For example, a child may be delayed in speech (i.e., unable to produce intelligible speech sounds), but not delayed in language because they use a Sign Language. Additionally, language delay encompasses the entirety of language developmental progress being slowed and not just the speech aspects. Language delays are recognized by comparing language development of children to recognized developmental milestones. They are presented in a variety of ways, as every individual child has a unique set of language skills and deficiencies that are identifiable through many different screenings and tools. There are different causes leading to language delay; it is often a result of another developmental disorder and treatment requires analysis of the unique individual causes. The condition is frequently observed early on, among two- and three-year-olds. Early language delays are only considered risk-factors in leading to more severe language disorders.

Reference
Wiki: Delayed speech and language development

    Delpire-McNeill syndrome (DELMNES) is a neurodevelopmental disorder with highly variable manifestations. Patients present in infancy with global developmental delay, including motor, speech, and impaired intellectual development. The most severely affected patients have hypotonia, inability to hold their head or walk, bilateral sensorineural deafness, and absent language, whereas others have delayed walking and mild to moderate intellectual disability, often with speech delay and autistic features. More variable features may include spasticity or minor involvement of other organ systems, such as hip dislocation or ventricular septal defect.

Reference
OMIM: Delpire-McNeill syndrome

    Dementia with Lewy bodies (DLB) is a type of dementia characterized by changes in sleep, behavior, cognition, movement, and regulation of automatic bodily functions. Memory loss is not always an early symptom. The disease worsens over time and is usually diagnosed when cognitive impairment interferes with normal daily functioning. Together with Parkinson's disease dementia, DLB is one of the two Lewy body dementias. It is a common form of dementia, but the prevalence is not known accurately and many diagnoses are missed. The disease was first described on autopsy by Kenji Kosaka in 1976, and he named the condition several years later. REM sleep behavior disorder (RBD)¡ªin which people lose the muscle paralysis (atonia) that normally occurs during REM sleep and act out their dreams¡ªis a core feature. RBD may appear years or decades before other symptoms. Other core features are visual hallucinations, marked fluctuations in attention or alertness, and parkinsonism (slowness of movement, trouble walking, or rigidity). A presumptive diagnosis can be made if several disease features or biomarkers are present; the diagnostic workup may include blood tests, neuropsychological tests, imaging, and sleep studies. A definitive diagnosis usually requires an autopsy. Most people with DLB do not have affected family members, although occasionally DLB runs in a family. The exact cause is unknown but involves formation of abnormal clumps of protein in neurons throughout the brain. Manifesting as Lewy bodies (discovered in 1912 by Frederic Lewy) and Lewy neurites, these clumps affect both the central and the autonomic nervous systems. Heart function and every level of gastrointestinal function¡ªfrom chewing to defecation¡ªcan be affected, constipation being one of the most common symptoms. Low blood pressure upon standing can also occur. DLB commonly causes psychiatric symptoms, such as altered behavior, depression, or apathy. DLB typically begins after the age of fifty, and people with the disease have an average life expectancy, with wide variability, of about four years after diagnosis. There is no cure or medication to stop the disease from progressing, and people in the latter stages of DLB may be unable to care for themselves. Treatments aim to relieve some of the symptoms and reduce the burden on caregivers. Medicines such as donepezil and rivastigmine can temporarily improve cognition and overall functioning, and melatonin can be used for sleep-related symptoms. Antipsychotics are usually avoided, even for hallucinations, because severe reactions occur in almost half of people with DLB, and their use can result in death. Management of the many different symptoms is challenging, as it involves multiple specialties and education of caregivers.

Reference
Wiki: Dementia with Lewy bodies

    An electroclinical syndrome characterized by epileptiform activity and at least one other pathology that together contribute to cognitive and behavioral impairments including developmental delay or regression with onset anywhere from birth to adulthood.

Reference
DiseaseOntology: Developmental and epileptic encephalopathy

    The term developmental delay can refer to: Global developmental delay, an umbrella term used when children are significantly delayed in two or more areas of development Specific developmental disorder, a classification of disorders characterized by delayed development Intellectual disability, generalized neurodevelopmental disorder characterized by significantly impaired intellectual and adaptive functioning Developmental disability, diverse group of chronic conditions, comprising mental or physical impairments that arise before adulthood Pervasive developmental disorder, a classification of disorders by delays in basic functions

Reference
Wiki: Developmental delay

    Diabetic neuropathy is various types of nerve damage associated with diabetes mellitus. Symptoms depend on the site of nerve damage and can include motor changes such as weakness; sensory symptoms such as numbness, tingling, or pain; or autonomic changes such as urinary symptoms. These changes are thought to result from a microvascular injury involving small blood vessels that supply nerves (vasa nervorum). Relatively common conditions which may be associated with diabetic neuropathy include distal symmetric polyneuropathy; third, fourth, or sixth cranial nerve palsy;[1] mononeuropathy; mononeuropathy multiplex; diabetic amyotrophy; and autonomic neuropathy.

Reference
Wiki: Diabetic neuropathy

    Long ear is a condition in which the ears are unusually long from top to bottom. This is defined as the median longitudinal ear length being over 2 SD from the mean external ear length (superior to inferior aspect).[1][2][3]

Reference
Wiki: Diets-Jongmans syndrome

    Diffuse midline glioma, H3 K27-altered (DMG) is a fatal tumour that arises in midline structures of the brain, most commonly the brainstem, thalamus and spinal cord. When located in the pons it is also known as diffuse intrinsic pontine glioma (DIPG).[3]

Reference
Wiki: Diffuse intrinsic pontine glioma

    Arthrogryposis (AMC) describes congenital joint contracture in two or more areas of the body. It derives its name from Greek, literally meaning 'curving of joints' (arthron, 'joint'; gr?p¨­sis, late Latin form of late Greek gr¨±p¨­sis, 'hooking'). Children born with one or more joint contractures have abnormal fibrosis of the muscle tissue causing muscle shortening, and therefore are unable to perform active extension and flexion in the affected joint or joints. AMC has been divided into three groups: amyoplasia, distal arthrogryposis, and syndromic. Amyoplasia is characterized by severe joint contractures and muscle weakness. Distal arthrogryposis mainly involves the hands and feet. Types of arthrogryposis with a primary neurological or muscle disease belong to the syndromic group.

Reference
Wiki: Distal arthrogryposis

    Distal hereditary motor neuronopathies (distal HMN, dHMN), sometimes also called distal hereditary motor neuropathies, are a genetically and clinically heterogeneous group of motor neuron diseases that result from genetic mutations in various genes and are characterized by degeneration and loss of motor neuron cells in the anterior horn of the spinal cord and subsequent muscle atrophy. Although they can hardly be distinguished from hereditary motor and sensory neuropathies on the clinical level, dHMNs are considered a separate class of disorders. Another common system of classification groups many of DHMNs under the heading of spinal muscular atrophies.

Reference
Wiki: Distal hereditary motor neuronopathy

    Spinal muscular atrophy (SMA) is a rare neuromuscular disorder that results in the loss of motor neurons and progressive muscle wasting. It is usually diagnosed in infancy or early childhood and if left untreated it is the most common genetic cause of infant death. It may also appear later in life and then have a milder course of the disease. The common feature is progressive weakness of voluntary muscles, with arm, leg and respiratory muscles being affected first. Associated problems may include poor head control, difficulties swallowing, scoliosis, and joint contractures. The age of onset and the severity of symptoms form the basis of the traditional classification of spinal muscular atrophy into a number of types. Spinal muscular atrophy is due to an abnormality (mutation) in the SMN1 gene which encodes SMN, a protein necessary for survival of motor neurons. Loss of these neurons in the spinal cord prevents signalling between the brain and skeletal muscles. Another gene, SMN2, is considered a disease modifying gene, since usually the more the SMN2 copies, the milder is the disease course. The diagnosis of SMA is based on symptoms and confirmed by genetic testing. Usually, the mutation in the SMN1 gene is inherited from both parents in an autosomal recessive manner, although in around 2% of cases it occurs during early development (de novo). The incidence of spinal muscular atrophy worldwide varies from about 1 in 4,000 births to around 1 in 16,000 births, with 1 in 7,000 and 1 in 10,000 commonly quoted for Europe and the US respectively. Outcomes in the natural course of the disease vary from death within a few weeks after birth in the most acute cases to normal life expectancy in the protracted SMA forms. The introduction of causative treatments in 2016 has significantly improved the outcomes. Medications that target the genetic cause of the disease include nusinersen, risdiplam, and the gene therapy medication onasemnogene abeparvovec. Supportive care includes physical therapy, occupational therapy, respiratory support, nutritional support, orthopaedic interventions, and mobility support.

Reference
Wiki: Distal spinal muscular atrophy

    A developmental and epileptic encephalopathy characterized by onset of seizures that are usually refractory to treatment in the first year of life after normal early development and impaired psychomoter development starting around the second year of life that has_material_basis_in heterozygous mutation in the SCN1A gene on chromosome 2q24.

Reference
DiseaseOntology: Dravet syndrome

    Dysarthria is a speech sound disorder resulting from neurological injury of the motor component of the motor¨Cspeech system and is characterized by poor articulation of phonemes. In other words, it is a condition in which problems effectively occur with the muscles that help produce speech, often making it very difficult to pronounce words. It is unrelated to problems with understanding language (that is, dysphasia or aphasia), although a person can have both. Any of the speech subsystems (respiration, phonation, resonance, prosody, and articulation) can be affected, leading to impairments in intelligibility, audibility, naturalness, and efficiency of vocal communication. Dysarthria that has progressed to a total loss of speech is referred to as anarthria. The term dysarthria was formed from the Greek components dys- "dysfunctional, impaired" and arthr- "joint, vocal articulation". Neurological injury due to damage in the central or peripheral nervous system may result in weakness, paralysis, or a lack of coordination of the motor¨Cspeech system, producing dysarthria. These effects in turn hinder control over the tongue, throat, lips or lungs; for example, swallowing problems (dysphagia) are also often present in those with dysarthria. Cranial nerves that control the muscles relevant to dysarthria include the trigeminal nerve's motor branch (V), the facial nerve (VII), the glossopharyngeal nerve (IX), the vagus nerve (X), and the hypoglossal nerve (XII). Dysarthria does not include speech disorders from structural abnormalities, such as cleft palate and must not be confused with apraxia of speech, which refers to problems in the planning and programming aspect of the motor¨Cspeech system. Just as the term "articulation" can mean either "speech" or "joint movement", so is the combining form of arthr- the same in the terms "dysarthria", "dysarthrosis", and "arthropathy"; the term "dysarthria" is conventionally reserved for the speech problem and is not used to refer to arthropathy, whereas "dysarthrosis" has both senses but usually refers to arthropathy.

Reference
Wiki: Dysarthria

    Ohtahara syndrome (OS), also known as Early Infantile Developmental & Epileptic Encephalopathy (EIDEE) is a progressive epileptic encephalopathy. The syndrome is outwardly characterized by tonic spasms and partial seizures within the first few months of life, and receives its more elaborate name from the pattern of burst activity on an electroencephalogram (EEG). It is an extremely debilitating progressive neurological disorder, involving intractable seizures and severe intellectual disabilities. No single cause has been identified, although in many cases structural brain damage is present.

Reference
Wiki: Early infantile epileptic encephalopathy

    Early myoclonic encephalopathy (EME) is a rare neonatal-onset epilepsy developmental and epileptic encephalopathy (DEE) with an onset at neonatal period or during the first 3 months of life. This syndrome is now included as part of the Early infantile developmental and epileptic encephalopathy (EIDEE) under the 2022 ILAE (International League Against Epilepsy) syndrome classification.

Reference
Wiki: Early myoclonic encephalopathy

    Developmental and epileptic encephalopathy-47 (DEE47) is a neurologic disorder characterized by onset of intractable seizures in the first days or weeks of life. EEG shows background slowing and multifocal epileptic spikes, and may show hypsarrhythmia. Most patients have developmental regression after seizure onset and show persistent intellectual disability and neurologic impairment, although the severity is variable. Treatment with phenytoin, a voltage-gated sodium channel blocker, may be beneficial (summary by Guella et al., 2016).

Reference
OMIM: EEF1A2-related developmental and degenerative epileptic-dyskinetic encephalopathy

    A central nervous system tumor (CNS tumor) is an abnormal growth of cells from the tissues of the brain or spinal cord. CNS tumor is a generic term encompassing over 120 distinct tumor types. Common symptoms of CNS tumors include vomiting, headache, changes in vision, nausea, and seizures. A CNS tumor can be detected and classified via neurological examination, medical imaging, such as x-ray imaging, magnetic resonance imaging (MRI) or computed tomography (CT), or after analysis of a biopsy.

Reference
Wiki: Embryonal central nervous system tumor

    A brain disease that is characterized by the occurrance of at least two unprovoked seizures resulting from a persistent epileptogenic abnormality of the brain that is able to spontaneously generate paroxysmal activity and typically manifested by sudden brief episodes of altered or diminished consciousness, involuntary movements, or convulsions.

Reference
DiseaseOntology: Epilepsy

    Encephalopathy (; from Ancient Greek: ?¦Í¦Ê?¦Õ¦Á¦Ë¦Ï? "brain" + ¦Ð?¦È¦Ï? "suffering") means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of overall brain dysfunction; this syndrome has many possible organic and inorganic causes.

Reference
Wiki: Epileptic encephalopathy

    Episodic ataxia (EA) is an autosomal dominant disorder characterized by sporadic bouts of ataxia (severe discoordination) with or without myokymia (continuous muscle movement). There are seven types recognized but the majority are due to two recognized entities. Ataxia can be provoked by psychological stress or startle, or heavy exertion, including exercise. Symptoms can first appear in infancy. There are at least six loci for EA, of which 4 are known genes. Some patients with EA also have migraine or progressive cerebellar degenerative disorders, symptomatic of either familial hemiplegic migraine or spinocerebellar ataxia. Some patients respond to acetazolamide though others do not.

Reference
Wiki: Episodic ataxia

    Ethylmalonic encephalopathy (EE) is a rare autosomal recessive inborn error of metabolism. Patients affected with EE are typically identified shortly after birth, with symptoms including diarrhea, petechiae and seizures. The genetic defect in EE is thought to involve an impairment in the degradation of sulfide intermediates in the body. Hydrogen sulfide then builds up to toxic levels. EE was initially described in 1994. Most cases of EE have been described in individuals of Mediterranean or Arabic origin.

Reference
Wiki: Ethylmalonic encephalopathy

    Amyotrophic lateral sclerosis (ALS), also known as motor neurone disease (MND) or Lou Gehrig's disease in the United States, is a rare, terminal neurodegenerative disorder that results in the progressive loss of both upper and lower motor neurons that normally control voluntary muscle contraction.[3] ALS is the most common form of the motor neuron diseases.[8] ALS often presents in its early stages with gradual muscle stiffness, twitches, weakness, and wasting.[3] Motor neuron loss typically continues until the abilities to eat, speak, move, and, lastly, breathe are all lost.[3] While only 15% of people with ALS also fully develop frontotemporal dementia, an estimated 50% face at least some minor difficulties with thinking and behavior.[9] Depending on which of the aforementioned symptoms develops first, ALS is classified as limb-onset (begins with weakness in the arms or legs) or bulbar-onset (begins with difficulty in speaking or swallowing).[10]

Reference
Wiki: Familial amyotrophic lateral sclerosis

    Familial dysautonomia (FD), also known as Riley-Day syndrome, is a rare, progressive, recessive genetic disorder of the autonomic nervous system that affects the development and survival of sensory, sympathetic, and some parasympathetic neurons in the autonomic and sensory nervous system. FD results in variable symptoms, including insensitivity to pain, inability to produce tears, poor growth, and labile blood pressure (episodic hypertension and postural hypotension). People with FD have frequent vomiting crises, pneumonia, problems with speech and movement, difficulty swallowing, and inappropriate perception of heat, pain and taste, as well as unstable blood pressure and gastrointestinal dysmotility. Originally reported by Drs. Conrad Milton Riley and Richard Lawrence Day in 1949, FD is one example of a group of disorders known as hereditary sensory and autonomic neuropathies (HSANs). All HSANs are characterized by widespread sensory dysfunction and variable autonomic dysfunction caused by incomplete development of sensory and autonomic neurons. The disorders are believed to be genetically distinct from each other.

Reference
Wiki: Familial dysautonomia

    A peripheral neuropathy characterized by recurrent, stereotyped, episodic intense pain, occurring predominantly in either the upper body or lower limbs, which is triggered or exacerbated by fatigue, cold exposure, fasting, weather changes and/or physical stress or exertion.

Reference
DiseaseOntology: familial episodic pain syndrome

    Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength. Hypotonia is a lack of resistance to passive movement, whereas muscle weakness results in impaired active movement. Central hypotonia originates from the central nervous system, while peripheral hypotonia is related to problems within the spinal cord, peripheral nerves and/or skeletal muscles. Severe hypotonia in infancy is commonly known as floppy baby syndrome. Recognizing hypotonia, even in early infancy, is usually relatively straightforward, but diagnosing the underlying cause can be difficult and often unsuccessful. The long-term effects of hypotonia on a child's development and later life depend primarily on the severity of the muscle weakness and the nature of the cause. Some disorders have a specific treatment but the principal treatment for most hypotonia of idiopathic or neurologic cause is physical therapy and/or occupational therapy for remediation. Hypotonia is thought to be associated with the disruption of afferent input from stretch receptors and/or lack of the cerebellum¡¯s facilitatory efferent influence on the fusimotor system, the system that innervates intrafusal muscle fibers thereby controlling muscle spindle sensitivity. On examination a diminished resistance to passive movement will be noted and muscles may feel abnormally soft and limp on palpation. Diminished deep tendon reflexes also may be noted. Hypotonia is a condition that can be helped with early intervention.

Reference
Wiki: Familial infantile myasthenia

    Metachromatic leukodystrophy (MLD) is a lysosomal storage disease which is commonly listed in the family of leukodystrophies as well as among the sphingolipidoses as it affects the metabolism of sphingolipids. Leukodystrophies affect the growth and/or development of myelin, the fatty covering which acts as an insulator around nerve fibers throughout the central and peripheral nervous systems. MLD involves cerebroside sulfate accumulation.[1][2] Metachromatic leukodystrophy, like most enzyme deficiencies, has an autosomal recessive inheritance pattern.[2]

Reference
Wiki: Fatal infantile leukodystrophy

    A dementia characterized by progressive neuronal loss predominantly involving the frontal and/or temporal lobes of the brain resulting in a gradual and progressive decline in behavior or language.

Reference
DiseaseOntology: Frontotemporal dementia

    Frontotemporal dementia (FTD), also called frontotemporal degeneration disease or frontotemporal neurocognitive disorder, encompasses several types of dementia involving the progressive degeneration of the brain's frontal and temporal lobes. FTD is the second most prevalent type of early onset dementia after Alzheimer's disease. Men and women appear to be equally affected. FTD generally presents as a behavioral or language disorder with gradual onset. Signs and symptoms tend to appear in late adulthood, typically between the ages of 45 and 65, although it can affect people younger or older than this. Currently, no cure or approved symptomatic treatment for FTD exists, although some off-label drugs and behavioral methods are prescribed. Features of FTD were first described by Arnold Pick between 1892 and 1906. The name Pick's disease was coined in 1922. This term is now reserved only for the behavioral variant of FTD, in which characteristic Pick bodies and Pick cells are present. These were first described by Alois Alzheimer in 1911. Common signs and symptoms include significant changes in social and personal behavior, disinhibition, apathy, blunting and dysregulation of emotions, and deficits in both expressive and receptive language. Each FTD subtype is relatively rare. FTDs are mostly early onset syndromes linked to frontotemporal lobar degeneration (FTLD), which is characterized by progressive neuronal loss predominantly involving the frontal or temporal lobes, and a typical loss of more than 70% of spindle neurons, while other neuron types remain intact. The three main subtypes or variant syndromes are a behavioral variant (bvFTD) previously known as Pick's disease, and two variants of primary progressive aphasia (PPA): semantic (svPPA) and nonfluent (nfvPPA). Two rare distinct subtypes of FTD are neuronal intermediate filament inclusion disease (NIFID) and basophilic inclusion body disease (BIBD). Other related disorders include corticobasal syndrome (CBS or CBD), and FTD with amyotrophic lateral sclerosis (ALS).

Reference
Wiki: Frontotemporal lobe degeneration

    A ganglioglioma (or gangliocytoma) is a rare, slow-growing primary central nervous system (CNS) tumor which most frequently occurs in the temporal lobes of children and young adults. They are mixed cell tumors containing both neural ganglionic cells and neural glial cell components.

Reference
Wiki: Ganglioglioma

    Conjugate gaze palsies are neurological disorders affecting the ability to move both eyes in the same direction. These palsies can affect gaze in a horizontal, upward, or downward direction. These entities overlap with ophthalmoparesis and ophthalmoplegia.

Reference
Wiki: Gaze palsy

    Giant axonal neuropathy is a rare, autosomal recessive neurological disorder that causes disorganization of neurofilaments. Neurofilaments form a structural framework that helps to define the shape and size of neurons and are essential for normal nerve function. A distinguishing feature is its association with kinky, or curly, hair; in such cases it has been called Giant axonal neuropathy with curly hair.

Reference
Wiki: Giant axonal neuropathy

    Glioblastoma, previously known as glioblastoma multiforme (GBM), is the most aggressive and most common type of cancer that originates in the brain, and has a very poor prognosis for survival. Initial signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality changes, nausea, and symptoms similar to those of a stroke. Symptoms often worsen rapidly and may progress to unconsciousness. The cause of most cases of glioblastoma is not known. Uncommon risk factors include genetic disorders, such as neurofibromatosis and Li¨CFraumeni syndrome, and previous radiation therapy. Glioblastomas represent 15% of all brain tumors. They are thought to arise from astrocytes. The diagnosis typically is made by a combination of a CT scan, MRI scan, and tissue biopsy. There is no known method of preventing the cancer. Treatment usually involves surgery, after which chemotherapy and radiation therapy are used. The medication temozolomide is frequently used as part of chemotherapy. High-dose steroids may be used to help reduce swelling and decrease symptoms. Surgical removal (decompression) of the tumor is linked to increased survival, but only by some months. Despite maximum treatment, the cancer almost always recurs. The typical duration of survival following diagnosis is 10¨C13 months, with fewer than 5¨C10% of people surviving longer than five years. Without treatment, survival is typically three months. It is the most common cancer that begins within the brain and the second-most common brain tumor, after meningioma, which is benign in most cases. About 3 in 100,000 people develop the disease per year. The average age at diagnosis is 64, and the disease occurs more commonly in males than females. Tumors of the central nervous system are the 10th leading cause of death worldwide, with up to 90% being brain tumors. Glioblastoma multiforme (GBM) is derived from astrocytes and accounts for 49% of all malignant central nervous system tumors, making it the most common form of central nervous system cancer. Despite countless efforts to develop new therapies for GBM over the years, the median survival rate of GBM patients worldwide is a dismal 8 months, with radiation and chemotherapy standard-of-care treatment beginning shortly after diagnosis only improving median survival length to around 14 months and a five-year survival rate of 5-10%. Similarly, the five-year survival rate for individuals with any form of primary malignant brain tumor is only 20%. The challenges associated with successfully treating brain cancers are numerous. In the simplest terms, brain tumors often occur in areas too difficult or dangerous to surgically resect, and most drug therapeutics are incapable of crossing the blood-brain barrier in sufficient quantities to stop tumor growth. Furthermore, while stereotactic radiosurgery-based approaches have proved to be effective for ablating a variety of brain tumors visible to MRI and other neuroimaging, metastatic brain cancers maintain high recurrence rates, with GBM recurrence seemingly inevitable.

Reference
Wiki: Glioblastoma

    Glioblastoma, previously known as glioblastoma multiforme (GBM), is the most aggressive and most common type of cancer that originates in the brain, and has a very poor prognosis for survival.[6][7][8] Initial signs and symptoms of glioblastoma are nonspecific.[1] They may include headaches, personality changes, nausea, and symptoms similar to those of a stroke.[1] Symptoms often worsen rapidly and may progress to unconsciousness.[2]

Reference
Wiki: Glioblastoma multiforme

    Melancholia or melancholy (from Greek: ¦Ì?¦Ë¦Á¦É¦Í¦Á ¦Ö¦Ï¦Ë? melaina chole, meaning black bile) is a concept found throughout ancient, medieval, and premodern medicine in Europe that describes a condition characterized by markedly depressed mood, bodily complaints, and sometimes hallucinations and delusions. Melancholy was regarded as one of the four temperaments matching the four humours. Until the 18th century, doctors and other scholars classified melancholic conditions as such by their perceived common cause ¨C an excess of a notional fluid known as "black bile", which was commonly linked to the spleen. Hippocrates and other ancient physicians described melancholia as a distinct disease with mental and physical symptoms, including persistent fears and despondencies, poor appetite, abulia, sleeplessness, irritability, and agitation. Later, fixed delusions were added by Galen and other physicians to the list of symptoms. In the Middle Ages, the understanding of melancholia shifted to a religious perspective, with sadness seen as a vice and demonic possession, rather than somatic causes, as a potential cause of the disease. During the late 16th and early 17th centuries, a cultural and literary cult of melancholia emerged in England, linked to Neoplatonist and humanist Marsilio Ficino's transformation of melancholia from a sign of vice into a mark of genius. This fashionable melancholy became a prominent theme in literature, art, and music of the era. Between the late 18th and late 19th centuries, melancholia was a common medical diagnosis. In this period, the focus was on the abnormal beliefs associated with the disorder, rather than depression and affective symptoms. In the 19th century, melancholia was considered to be rooted in subjective 'passions' that seemingly caused disordered mood (in contrast to modern biomedical explanations for mood disorders). In Victorian Britain, the notion of melancholia as a disease evolved as it became increasingly classifiable and diagnosable with a set list of symptoms that contributed to a biomedical model for the understanding mental disease. However, in the 20th century, the focus again shifted, and the term became used essentially as a synonym for depression. Indeed, modern concepts of depression as a mood disorder eventually arose from this historical context. Today, the term "melancholia" and "melancholic" are still used in medical diagnostic classification, such as in ICD-11 and DSM-5, to specify certain features that may be present in major depression. Related terms used in historical medicine include lugubriousness (from Latin lugere: "to mourn"), moroseness (from Latin morosus: "self-will or fastidious habit"), wistfulness (from a blend of "wishful" and the obsolete English wistly, meaning "intently"), and saturnineness (from Latin Saturninus: "of the planet Saturn).

Reference
Wiki: Glioma

    A glioma is a type of tumor that starts in the glial cells of the brain or the spine.[2] Gliomas comprise about 30 percent of all brain tumors and central nervous system tumours, and 80 percent of all malignant brain tumours.[3]

Reference
Wiki: Glioma/adult gliomas

    Global developmental delay is an umbrella term used when children are significantly delayed in two or more areas of development. It can be diagnosed when a child is delayed in one or more milestones, categorised into motor skills, speech, cognitive skills, and social and emotional development.[1] There is usually a specific condition which causes this delay, such as Cerebral Palsy, Fragile X syndrome or other chromosomal abnormalities. However, it is sometimes difficult to identify this underlying condition.[2]

Reference
Wiki: Global developmental delay

    GM1-gangliosidosis is an autosomal recessive lysosomal storage disease characterized by accumulation of ganglioside substrates in lysosomes. Clinically, patients show variable degrees of neurodegeneration and skeletal abnormalities. There are 3 main clinical variants categorized by severity and variable residual beta-galactosidase activity. Type I, or infantile form (GM1G1), shows rapid psychomotor deterioration beginning within 6 months of birth, generalized central nervous system involvement, hepatosplenomegaly, facial dysmorphism, macular cherry-red spots, skeletal dysplasia, and early death. Type II, or late-infantile/juvenile form (GM1G2; 230600), has onset between 7 months and 3 years, shows generalized central nervous system involvement with psychomotor deterioration, seizures, localized skeletal involvement, and survival into childhood. Hepatosplenomegaly and cherry-red spots are usually not present. Type III, or adult/chronic form (GM1G3; 230650), shows onset from 3 to 30 years and is characterized by localized skeletal involvement and localized central nervous system involvement, such as dystonia or gait or speech disturbance. There is an inverse correlation between disease severity and residual enzyme activity.

Reference
OMIM: GM1-gangliosidosis

    The GM2-gangliosidoses are a group of disorders caused by excessive accumulation of ganglioside GM2 and related glycolipids in the lysosomes, mainly of neuronal cells. GM2-gangliosidosis AB variant is characterized by normal hexosaminidase A (HEXA; 606869) and hexosaminidase B (HEXB; 606873) but the inability to form a functional GM2 activator complex. The clinical and biochemical phenotype of the AB variant is very similar to that of classic Tay-Sachs disease (see 272800) (Gravel et al., 2001).

Reference
OMIM: GM2-gangliosidosis

    A mitochondrial disorder characterized by fetal growth restriction, aminoaciduria, cholestasis, iron overload, lactocidosis, and early death that has_material_basis_in homozygous or compound heterozygous mutation in the BCS1L gene on chromosome 2q35.

Reference
DiseaseOntology: GRACILE syndrome

    Amyotrophic lateral sclerosis (ALS), also known as motor neurone disease (MND) or Lou Gehrig's disease in the United States, is a rare but terminal neurodegenerative disorder that results in the progressive loss of both upper and lower motor neurons that normally control voluntary muscle contraction. ALS is the most common form of the motor neuron diseases. ALS often presents in its early stages with gradual muscle stiffness, twitches, weakness, and wasting. Motor neuron loss typically continues until the abilities to eat, speak, move, and, lastly, breathe are all lost. While only 15% of people with ALS also fully develop frontotemporal dementia, an estimated 50% face at least some minor difficulties with thinking and behavior. Depending on which of the aforementioned symptoms develops first, ALS is classified as limb-onset (begins with weakness in the arms or legs) or bulbar-onset (begins with difficulty in speaking or swallowing). Most cases of ALS (about 90% to 95%) have no known cause, and are known as sporadic ALS. However, both genetic and environmental factors are believed to be involved. The remaining 5% to 10% of cases have a genetic cause, often linked to a history of the disease in the family, and these are known as familial ALS (hereditary). About half of these genetic cases are due to disease-causing variants in one of four specific genes. The diagnosis is based on a person's signs and symptoms, with testing conducted to rule out other potential causes. There is no known cure for ALS. The goal of treatment is to slow the disease progression, and improve symptoms. Treatments that slow ALS include riluzole (extends life by two to three months) and sodium phenylbutyrate/ursodoxicoltaurine (extends life by around seven months). Non-invasive ventilation may result in both improved quality, and length of life. Mechanical ventilation can prolong survival but does not stop disease progression. A feeding tube may help maintain weight and nutrition. Death is usually caused by respiratory failure. The disease can affect people of any age, but usually starts around the age of 60. The average survival from onset to death is two to four years, though this can vary, and about 10% of those affected survive longer than ten years. Descriptions of the disease date back to at least 1824 by Charles Bell. In 1869, the connection between the symptoms and the underlying neurological problems was first described by French neurologist Jean-Martin Charcot, who in 1874 began using the term amyotrophic lateral sclerosis.

Reference
Wiki: Guam amyotrophic lateral sclerosis/parkinsonism-dementia complex

    Hereditary motor and sensory neuropathies (HMSN) is a name sometimes given to a group of different neuropathies which are all characterized by their impact upon both afferent and efferent neural communication. HMSN are characterised by atypical neural development and degradation of neural tissue. The two common forms of HMSN are either hypertrophic demyelinated nerves or complete atrophy of neural tissue. Hypertrophic condition causes neural stiffness and a demyelination of nerves in the peripheral nervous system, and atrophy causes the breakdown of axons and neural cell bodies. In these disorders, a patient experiences progressive muscle atrophy and sensory neuropathy of the extremities. The term "hereditary motor and sensory neuropathy" was used mostly historically to denote the more common forms Charcot¨CMarie¨CTooth disease (CMT). With the identification of a wide number of genetically and phenotypically distinct forms of CMT, the term HMSN is now used less frequently.

Reference
Wiki: Hereditary motor and sensory neuropathy

    Hereditary neuralgic amyotrophy (HNA) is a neuralgic disorder that is characterized by nerve damage and muscle atrophy, preceded by severe pain.[1] In about half of the cases it is associated with a mutation of the SEPT9 gene (17q25). While not much is known about this disorder, it has been characterized to be similar to Parsonage-Turner syndrome in prognosis.

Reference
Wiki: Hereditary neuralgic amyotrophy

    A paraganglioma is a rare neuroendocrine neoplasm that may develop at various body sites (including the head, neck, thorax and abdomen). When the same type of tumor is found in the adrenal gland, they are referred to as a pheochromocytoma. They are rare tumors, with an overall estimated incidence of 1 in 300,000.[1] There is no test that determines benign from malignant tumors; long-term follow-up is therefore recommended for all individuals with paraganglioma.[2]

Reference
Wiki: Hereditary paraganglioma

    Hereditary sensory and autonomic neuropathy (HSAN) or hereditary sensory neuropathy (HSN) is a condition used to describe any of the types of this disease which inhibit sensation. They are less common than Charcot-Marie-Tooth disease.

Reference
Wiki: Hereditary sensory and autonomic neuropathy

    Hereditary sensory and autonomic neuropathy (HSAN) or hereditary sensory neuropathy (HSN) is a condition used to describe any of the types of this disease which inhibit sensation. They are less common than Charcot-Marie-Tooth disease.

Reference
Wiki: Hereditary sensory neuropathy

    Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive gait disorder. The disease presents with progressive stiffness (spasticity) and contraction in the lower limbs. HSP is also known as hereditary spastic paraparesis, familial spastic paraplegia, French settlement disease, Strumpell disease, or Strumpell-Lorrain disease. The symptoms are a result of dysfunction of long axons in the spinal cord. The affected cells are the primary motor neurons; therefore, the disease is an upper motor neuron disease. HSP is not a form of cerebral palsy even though it physically may appear and behave much the same as spastic diplegia. The origin of HSP is different from cerebral palsy. Despite this, some of the same anti-spasticity medications used in spastic cerebral palsy are sometimes used to treat HSP symptoms. HSP is caused by defects in transport of proteins, structural proteins, cell-maintaining proteins, lipids, and other substances through the cell. Long nerve fibers (axons) are affected because long distances make nerve cells particularly sensitive to defects in these mentioned mechanisms. The disease was first described in 1880 by the German neurologist Adolph Str¨¹mpell. It was described more extensively in 1888 by Maurice Lorrain, a French physician. Due to their contribution in describing the disease, it is still called Str¨¹mpell-Lorrain disease in French-speaking countries. The term hereditary spastic paraplegia was coined by Anita Harding in 1983.

Reference
Wiki: Hereditary spastic paraplegia

    Hiatt-Neu-Cooper neurodevelopmental syndrome (HINCONS) is characterized by global developmental delay with delayed walking or inability to walk and impaired intellectual development with poor or absent speech. Affected individuals have axial hypotonia and dysmorphic facies. Additional more variable features may include seizures, autistic or behavioral abnormalities, and brain abnormalities, such as dysplastic corpus callosum or polymicrogyria (summary by Hiatt et al., 2018).

Reference
OMIM: Hiatt-Neu-Cooper neurodevelopmental syndrome

    Histone H4 is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N-terminal tail, H4 is involved with the structure of the nucleosome of the 'beads on a string' organization. Histone proteins are highly post-translationally modified. Covalently bonded modifications include acetylation and methylation of the N-terminal tails. These modifications may alter expression of genes located on DNA associated with its parent histone octamer. Histone H4 is an important protein in the structure and function of chromatin, where its sequence variants and variable modification states are thought to play a role in the dynamic and long term regulation of genes.

Reference
Wiki: HIST1H4C-associated disorder

    Neurodevelopmental disorders are a group of conditions that begin to emerge during childhood (or the development of the nervous system). According to the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (DSM-5) published in 2013, these conditions generally appear in early childhood, usually before children start school, and can persist into adulthood. The key characteristic of all these disorders is that they negatively impact a person's functioning in one or more domains of life (personal, social, academic, occupational) depending on the disorder and deficits it has caused. All of these disorders and their levels of impairment exist on a spectrum, and affected individuals can experience varying degrees of symptoms and deficits, despite having the same diagnosis. The DSM-5 classifies neurodevelopmental disorders into six overarching groups. Intellectual disability (intellectual development disorder) Communication disorders Autism spectrum disorder (ASD) Attention-deficit/hyperactivity disorder (ADHD) Neurodevelopmental motor disorders Specific learning disorders These disorders are commonly comorbid conditions, meaning that a person affected by one of these disorders will usually meet criteria for a second disorder.

Reference
Wiki: History of neurodevelopmental disorder

    Primary familial brain calcification (PFBC), also known as familial idiopathic basal ganglia calcification (FIBGC) and Fahr's disease, is a rare, genetically dominant or recessive, inherited neurological disorder characterized by abnormal deposits of calcium in areas of the brain that control movement. Through the use of CT scans, calcifications are seen primarily in the basal ganglia and in other areas such as the cerebral cortex.

Reference
Wiki: Idiopathic basal ganglia calcification

    Idiopathic generalized epilepsy (IGE) is a group of epileptic disorders that are believed to have a strong underlying genetic basis. IGE is considered a subgroup of Genetic Generalized Epilepsy (GGE). Patients with an IGE subtype are typically otherwise normal and have no structural brain abnormalities. People also often have a family history of epilepsy and seem to have a genetically predisposed risk of seizures. IGE tends to manifest itself between early childhood and adolescence although it can be eventually diagnosed later. The genetic cause of some IGE types is known, though inheritance does not always follow a simple monogenic mechanism.

Reference
Wiki: Idiopathic generalized epilepsy

    IgA nephropathy (IgAN), also known as Berger's disease (/b??r??e?/) (and variations), or synpharyngitic glomerulonephritis, is a disease of the kidney (or nephropathy) and the immune system; specifically it is a form of glomerulonephritis or an inflammation of the glomeruli of the kidney. Aggressive Berger's disease (a rarer form of the disease) can attack other major organs, such as the liver, skin and heart.

Reference
Wiki: IgA nephropathy

    Intellectual disability (ID), also known as general learning disability (in the United Kingdom) and mental retardation, is a generalized neurodevelopmental disorder characterized by significant impairment in intellectual and adaptive functioning that is first apparent during childhood. Children with intellectual disabilities typically have an intelligence quotient (IQ) below 70 and deficits in at least two adaptive behaviors that affect everyday, general living. According to the DSM-5, intellectual functions include reasoning, problem solving, planning, abstract thinking, judgment, academic learning, and learning from experience. Deficits in these functions must be confirmed by clinical evaluation and individualized standard IQ testing. On the other hand, adaptive behaviors include the social, developmental, and practical skills people learn to perform tasks in their everyday lives. Deficits in adaptive functioning often compromises an individual's independence and ability to meet their social responsibility. Intellectual disability is subdivided into syndromic intellectual disability, in which intellectual deficits associated with other medical and behavioral signs and symptoms are present, and non-syndromic intellectual disability, in which intellectual deficits appear without other abnormalities. Down syndrome and fragile X syndrome are examples of syndromic intellectual disabilities. Intellectual disability affects about 2 to 3% of the general population. Seventy-five to ninety percent of the affected people have mild intellectual disability. Non-syndromic, or idiopathic cases account for 30 to 50% of these cases. About a quarter of cases are caused by a genetic disorder, and about 5% of cases are inherited. Cases of unknown cause affect about 95 million people as of 2013.

Reference
Wiki: Intellectual developmental disorder

    Intellectual disability (ID), also known as general learning disability (in the United Kingdom) and mental retardation, is a generalized neurodevelopmental disorder characterized by significant impairment in intellectual and adaptive functioning that is first apparent during childhood. Children with intellectual disabilities typically have an intelligence quotient (IQ) below 70 and deficits in at least two adaptive behaviors that affect everyday, general living. According to the DSM-5, intellectual functions include reasoning, problem solving, planning, abstract thinking, judgment, academic learning, and learning from experience. Deficits in these functions must be confirmed by clinical evaluation and individualized standard IQ testing. On the other hand, adaptive behaviors include the social, developmental, and practical skills people learn to perform tasks in their everyday lives. Deficits in adaptive functioning often compromises an individual's independence and ability to meet their social responsibility. Intellectual disability is subdivided into syndromic intellectual disability, in which intellectual deficits associated with other medical and behavioral signs and symptoms are present, and non-syndromic intellectual disability, in which intellectual deficits appear without other abnormalities. Down syndrome and fragile X syndrome are examples of syndromic intellectual disabilities. Intellectual disability affects about 2 to 3% of the general population. Seventy-five to ninety percent of the affected people have mild intellectual disability. Non-syndromic, or idiopathic cases account for 30 to 50% of these cases. About a quarter of cases are caused by a genetic disorder, and about 5% of cases are inherited. Cases of unknown cause affect about 95 million people as of 2013.

Reference
Wiki: Intellectual disability

    Intellectual disability (ID), also known as general learning disability (in the United Kingdom) and mental retardation, is a generalized neurodevelopmental disorder characterized by significant impairment in intellectual and adaptive functioning that is first apparent during childhood. Children with intellectual disabilities typically have an intelligence quotient (IQ) below 70 and deficits in at least two adaptive behaviors that affect everyday, general living. According to the DSM-5, intellectual functions include reasoning, problem solving, planning, abstract thinking, judgment, academic learning, and learning from experience. Deficits in these functions must be confirmed by clinical evaluation and individualized standard IQ testing. On the other hand, adaptive behaviors include the social, developmental, and practical skills people learn to perform tasks in their everyday lives. Deficits in adaptive functioning often compromises an individual's independence and ability to meet their social responsibility. Intellectual disability is subdivided into syndromic intellectual disability, in which intellectual deficits associated with other medical and behavioral signs and symptoms are present, and non-syndromic intellectual disability, in which intellectual deficits appear without other abnormalities. Down syndrome and fragile X syndrome are examples of syndromic intellectual disabilities. Intellectual disability affects about 2 to 3% of the general population. Seventy-five to ninety percent of the affected people have mild intellectual disability. Non-syndromic, or idiopathic cases account for 30 to 50% of these cases. About a quarter of cases are caused by a genetic disorder, and about 5% of cases are inherited. Cases of unknown cause affect about 95 million people as of 2013.

Reference
Wiki: Intellectual functioning disability

    Generalized epilepsy with febrile seizures plus (GEFS+) is a syndromic autosomal dominant disorder where affected individuals can exhibit numerous epilepsy phenotypes.[1] GEFS+ can persist beyond early childhood (i.e., 6 years of age). GEFS+ is also now believed to encompass three other epilepsy disorders: severe myoclonic epilepsy of infancy (SMEI), which is also known as Dravet's syndrome, borderline SMEI (SMEB), and intractable epilepsy of childhood (IEC).[2][3] There are at least six types of GEFS+, delineated by their causative gene. Known causative gene mutations are in the sodium channel ¦Á subunit genes SCN1A, an associated ¦Â subunit SCN1B, and in a GABAA receptor ¦Ã subunit gene, in GABRG2 and there is another gene related with calcium channel the PCDH19 which is also known as Epilepsy Female with Mental Retardation.[4] Penetrance for this disorder is estimated at 60%.[5]

Reference
Wiki: Intractable childhood epilepsy with generalized tonic-clonic seizures

    Joubert syndrome is a rare autosomal recessive genetic disorder that affects the cerebellum, an area of the brain that controls balance and coordination. Joubert syndrome is one of the many genetic syndromes associated with syndromic retinitis pigmentosa. The syndrome was first identified in 1969 by pediatric neurologist Marie Joubert in Montreal, Quebec, Canada, while working at the Montreal Neurological Institute and McGill University.

Reference
Wiki: Joubert syndrome

    Amyotrophic lateral sclerosis (ALS), also known as motor neurone disease (MND) or Lou Gehrig's disease in the United States, is a rare but terminal neurodegenerative disorder that results in the progressive loss of both upper and lower motor neurons that normally control voluntary muscle contraction. ALS is the most common form of the motor neuron diseases. ALS often presents in its early stages with gradual muscle stiffness, twitches, weakness, and wasting. Motor neuron loss typically continues until the abilities to eat, speak, move, and, lastly, breathe are all lost. While only 15% of people with ALS also fully develop frontotemporal dementia, an estimated 50% face at least some minor difficulties with thinking and behavior. Depending on which of the aforementioned symptoms develops first, ALS is classified as limb-onset (begins with weakness in the arms or legs) or bulbar-onset (begins with difficulty in speaking or swallowing). Most cases of ALS (about 90% to 95%) have no known cause, and are known as sporadic ALS. However, both genetic and environmental factors are believed to be involved. The remaining 5% to 10% of cases have a genetic cause, often linked to a history of the disease in the family, and these are known as familial ALS (hereditary). About half of these genetic cases are due to disease-causing variants in one of four specific genes. The diagnosis is based on a person's signs and symptoms, with testing conducted to rule out other potential causes. There is no known cure for ALS. The goal of treatment is to slow the disease progression, and improve symptoms. Treatments that slow ALS include riluzole (extends life by two to three months) and sodium phenylbutyrate/ursodoxicoltaurine (extends life by around seven months). Non-invasive ventilation may result in both improved quality, and length of life. Mechanical ventilation can prolong survival but does not stop disease progression. A feeding tube may help maintain weight and nutrition. Death is usually caused by respiratory failure. The disease can affect people of any age, but usually starts around the age of 60. The average survival from onset to death is two to four years, though this can vary, and about 10% of those affected survive longer than ten years. Descriptions of the disease date back to at least 1824 by Charles Bell. In 1869, the connection between the symptoms and the underlying neurological problems was first described by French neurologist Jean-Martin Charcot, who in 1874 began using the term amyotrophic lateral sclerosis.

Reference
Wiki: Juvenile amyotrophic lateral sclerosis

    9q34 deletion syndrome is a rare genetic disorder. Terminal deletions of chromosome 9q34 have been associated with childhood hypotonia, a distinctive facial appearance and developmental disability. The facial features typically described include arched eyebrows, small head circumference, midface hypoplasia, prominent jaw and a pouting lower lip. Individuals with this disease may often have speech impediments, such as speech delays. Other characteristics of this disease include: epilepsy, congenital and urogenital defects, microcephaly, corpulence, and psychiatric disorders. From analysis of chromosomal breakpoints, as well as gene sequencing in suggestive cases, Kleefstra and colleagues identified EHMT1 as the causative gene. This gene is responsible for producing the protein histone methyltransferase which functions to alter histones. Ultimately, histone methyltransferases are important in deactivating certain genes, needed for proper growth and development. Moreover, a frameshift, missense, or nonsense error in the coding sequence of EHMT1 can result in this condition in an individual.

Reference
Wiki: Kleefstra syndrome

    Kufor¨CRakeb syndrome (KRS) is an autosomal recessive disorder of juvenile onset also known as Parkinson disease-9 (PARK9). It is named after Kufr Rakeb in Irbid, Jordan. Kufor¨CRakeb syndrome was first identified in this region in Jordan with a Jordanian couple's 5 children who had rigidity, mask-like face, and bradykinesia. The disease was first described in 1994 by Najim Al-Din et al. The OMIM number is 606693. Less than 50 individuals have been reported to have KRS. Typically, rapid onset of symptoms occurs between the ages of 12 and 16. It is important to conduct genetic testing to screen family members, so the disease can be detected early and symptoms can be managed. ATP13A2 gene mutations are associated with Kufor¨CRakeb syndrome, first identified in 2010. This syndrome is identified to have a compound heterozygous or homozygous mutation in the ATP13A2 gene. This mutation is located on chromosome 1 and codes for a lysosomal type 5 ATPase. Patients have been identified to have iron in their basal ganglia evident on MRI scans, which has led it to be included as a type of neurodegeneration with brain iron accumulation disorder. There are no current disease-modifying treatments so treatment focusses on improving symptoms and supportive therapies.

Reference
Wiki: Kufor-Rakeb syndrome

    Leber's hereditary optic neuropathy (LHON) is a mitochondrially inherited (transmitted from mother to offspring) degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss of central vision; it predominantly affects young adult males. LHON is transmitted only through the mother, as it is primarily due to mutations in the mitochondrial (not nuclear) genome, and only the egg contributes mitochondria to the embryo. Men cannot pass on the disease to their offspring.[1] LHON is usually due to one of three pathogenic mitochondrial DNA (mtDNA) point mutations. These mutations are at nucleotide positions 11778 G to A, 3460 G to A and 14484 T to C, respectively in the ND4, ND1 and ND6 subunit genes of complex I of the oxidative phosphorylation chain in mitochondria.

Reference
Wiki: Leber hereditary optic neuropathy

    Legius syndrome (LS) is an autosomal dominant condition characterized by cafe au lait spots. It was first described in 2007 and is often mistaken for neurofibromatosis type I. It is caused by mutations in the SPRED1 gene. It is also known as neurofibromatosis type 1-like syndrome.

Reference
Wiki: Legius syndrome

    Leukodystrophies are a group of, usually, inherited disorders, characterized by degeneration of the white matter in the brain. The word leukodystrophy comes from the Greek roots leuko, "white", dys, "abnormal" and troph, "growth". The leukodystrophies are caused by imperfect growth or development of the glial cells which produce the myelin sheath, the fatty insulating covering around nerve fibers. Leukodystrophies may be classified as hypomyelinating or demyelinating diseases, respectively, depending on whether the damage is present before birth or occurs after. While all leukodystrophies are the result of genetic mutations, other demyelinating disorders have an autoimmune, infectious, or metabolic etiology. When damage occurs to white matter, subsequent immune responses can lead to inflammation in the central nervous system (CNS), along with the loss of myelin. The degeneration of white matter can be seen in an MRI scan and is used to diagnose leukodystrophy. Leukodystrophy is characterized by specific symptoms, including decreased motor function, muscle rigidity, and eventual degeneration of sight and hearing. While the disease is fatal, the age of onset is a key factor, as infants have a typical life expectancy of 2¨C8 years, while adults typically live more than a decade after onset. Treatment options are limited, although hematopoietic stem cell transplantations using bone marrow or cord blood seem to help in certain leukodystrophy types, while further research is being done. The combined incidence of the leukodystrophies is estimated at 1 in 7,600. The majority of types involve the inheritance of an X-linked recessive, or X-linked dominant trait, while others, although involving a defective gene, are the result of spontaneous mutation rather than genetic inheritance.

Reference
Wiki: Leukodystrophy

    Lewy body dementia (LBD) is an umbrella term for two similar and common subtypes of dementia:[1] dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD).[2][3][4][5] Both are characterized by changes in thinking, movement, behavior, and mood.[1] The two conditions have similar features and may have similar causes, and are believed to belong on a spectrum of Lewy body disease[2] that includes Parkinson's disease.[5] As of 2014, they were more often misdiagnosed than any other common dementia.[6]

Reference
Wiki: Lewy body disease

    Li-Ghorbani-Weisz-Hubshman syndrome (LIGOWS) is a neurodevelopmental disorder characterized by global developmental delay, mild to moderately impaired intellectual development with language delay, and mild dysmorphic features. Affected individuals may have behavioral abnormalities and difficulties with numbers and understanding certain concepts, such as money. Some patients have seizures. Brain imaging often shows enlarged ventricles, thin corpus callosum, and gray matter nodular heterotopia, suggesting abnormal cortical brain development. More variable additional features may be present (summary by Li et al., 2020).

Reference
OMIM: Li-Ghorbani-Weisz-Hubshman syndrome

    Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introduced by a group of US clinicians in the mid-1970s, the term was adopted by the American Psychiatric Association for this symptom cluster under mood disorders in the 1980 version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III), and has become widely used since. The diagnosis of major depressive disorder is based on the person's reported experiences, behavior reported by relatives or friends, and a mental status examination. There is no laboratory test for the disorder, but testing may be done to rule out physical conditions that can cause similar symptoms. The most common time of onset is in a person's 20s, with females affected about twice as often as males. The course of the disorder varies widely, from one episode lasting months to a lifelong disorder with recurrent major depressive episodes. Those with major depressive disorder are typically treated with psychotherapy and antidepressant medication. Medication appears to be effective, but the effect may be significant only in the most severely depressed. Hospitalization (which may be involuntary) may be necessary in cases with associated self-neglect or a significant risk of harm to self or others. Electroconvulsive therapy (ECT) may be considered if other measures are not effective. Major depressive disorder is believed to be caused by a combination of genetic, environmental, and psychological factors, with about 40% of the risk being genetic. Risk factors include a family history of the condition, major life changes, certain medications, chronic health problems, and substance use disorders. It can negatively affect a person's personal life, work life, or education, and cause issues with a person's sleeping habits, eating habits, and general health. Major depressive disorder affected approximately 163 million people (2% of the world's population) in 2017. The percentage of people who are affected at one point in their life varies from 7% in Japan to 21% in France. Lifetime rates are higher in the developed world (15%) compared to the developing world (11%). The disorder causes the second-most years lived with disability, after lower back pain.

Reference
Wiki: Major depressive disorder

    A glioma is a type of tumor that starts in the glial cells of the brain or the spine.[2] Gliomas comprise about 30 percent of all brain tumors and central nervous system tumours, and 80 percent of all malignant brain tumours.[3]

Reference
Wiki: Malignant glioma

    MASA syndrome is a rare X-linked recessive neurological disorder on the L1 disorder spectrum belonging in the group of hereditary spastic paraplegias a paraplegia known to increase stiffness spasticity in the lower limbs. This syndrome also has two other names, CRASH syndrome and Gareis-Mason syndrome.

Reference
Wiki: MASA syndrome

    An infratentorial cancer that is located_in the lower part of the brain and is a type of primitive neuroectodermal tumor.

Reference
DiseaseOntology: Medulloblastoma

    Congenital melanocytic nevus syndrome is characterized by pigmentary skin defects apparent at birth. Most individuals have 1 or more large or giant lesions greater than 20 cm and up to over 60 cm in diameter, which may cover up to 80% of total body area. These lesions may or may not be hairy. Smaller 'satellite' pigmented lesions numbering in the hundreds may also be present all over the body. Congenital melanocytic nevi (CMN) can be associated with malignant melanoma (see CMM1, 155600), but the risk appears to be low, ranging from 1 to 2% for all individuals, but rising to 10 to 15% in those with very large nevi (greater than 40 cm). A small subset of patients with CMNS have abnormalities of the central nervous system, known as 'neurocutaneous melanosis' or 'neuromelanosis' (249400), which may be symptomatic. Patients with CMNS also tend to have a characteristic facial appearance, including wide or prominent forehead, periorbital fullness, small short nose with narrow nasal bridge, round face, full cheeks, prominent premaxilla, and everted lower lip (summary by Kinsler et al., 2008; Kinsler et al., 2012).

Reference
OMIM: Melanocytic nevus syndrome

    Intellectual disability (ID), also known as general learning disability (in the United Kingdom) and mental retardation, is a generalized neurodevelopmental disorder characterized by significant impairment in intellectual and adaptive functioning that is first apparent during childhood. Children with intellectual disabilities typically have an intelligence quotient (IQ) below 70 and deficits in at least two adaptive behaviors that affect everyday, general living. According to the DSM-5, intellectual functions include reasoning, problem solving, planning, abstract thinking, judgment, academic learning, and learning from experience. Deficits in these functions must be confirmed by clinical evaluation and individualized standard IQ testing. On the other hand, adaptive behaviors include the social, developmental, and practical skills people learn to perform tasks in their everyday lives. Deficits in adaptive functioning often compromises an individual's independence and ability to meet their social responsibility. Intellectual disability is subdivided into syndromic intellectual disability, in which intellectual deficits associated with other medical and behavioral signs and symptoms are present, and non-syndromic intellectual disability, in which intellectual deficits appear without other abnormalities. Down syndrome and fragile X syndrome are examples of syndromic intellectual disabilities. Intellectual disability affects about 2 to 3% of the general population. Seventy-five to ninety percent of the affected people have mild intellectual disability. Non-syndromic, or idiopathic cases account for 30 to 50% of these cases. About a quarter of cases are caused by a genetic disorder, and about 5% of cases are inherited. Cases of unknown cause affect about 95 million people as of 2013.

Reference
Wiki: Mental retardation

    Familial Amyloidosis, Finnish Type (FAF), also called hereditary gelsolin amyloidosis and AGel amyloidosis (AGel), is an amyloid condition with a number of associated cutaneous and neurological presentations deriving from the aberrant proteolysis of a mutated form of plasma gelsolin. First described in 1969 by the Finnish ophthalmologist Jouko Meretoja, FAF is uncommon with 400¨C600 cases described in Finland and 15 elsewhere.

Reference
Wiki: Meretoja syndrome

    A neurodegenerative disease that is located_in the motor neurons.

Reference
DiseaseOntology: Motor neuron disease

    Multiple congenital anomalies-hypotonia-seizures syndrome is a rare multi-systemic genetic disorder which is characterized by developmental delay, seizures, hypotonia and heart, urinary, and gastrointestinal abnormalities.

Reference
Wiki: Multiple congenital anomalies

    Muscle weakness is a lack of muscle strength. Its causes are many and can be divided into conditions that have either true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, including muscular dystrophy and inflammatory myopathy. It occurs in neuromuscular junction disorders, such as myasthenia gravis. Muscle weakness can also be caused by low levels of potassium and other electrolytes within muscle cells. It can be temporary or long-lasting (from seconds or minutes to months or years). The term myasthenia is from my- from Greek ¦Ì¦Ô¦Ï meaning "muscle" + -asthenia ?¦Ò¦È?¦Í¦Å¦É¦Á meaning "weakness".

Reference
Wiki: Muscle weakness

    Lambert¨CEaton myasthenic syndrome (LEMS) is a rare autoimmune disorder characterized by muscle weakness of the limbs. It is also known as myasthenic syndrome, Eaton¨CLambert syndrome, and when related to cancer, carcinomatous myopathy. Around 60% of those with LEMS have an underlying malignancy, most commonly small-cell lung cancer; it is therefore regarded as a paraneoplastic syndrome (a condition that arises as a result of cancer elsewhere in the body). It is the result of antibodies against presynaptic voltage-gated calcium channels, and likely other nerve terminal proteins, in the neuromuscular junction (the connection between nerves and the muscle that they supply). The diagnosis is usually confirmed with electromyography and blood tests; these also distinguish it from myasthenia gravis, a related autoimmune neuromuscular disease. If the disease is associated with cancer, direct treatment of the cancer often relieves the symptoms of LEMS. Other treatments often used are steroids, azathioprine, which suppress the immune system, intravenous immunoglobulin, which outcompetes autoreactive antibody for Fc receptors, and pyridostigmine and 3,4-diaminopyridine, which enhance the neuromuscular transmission. Occasionally, plasma exchange is required to remove the antibodies. The condition affects about 3.4 per million people. LEMS usually occurs in people over 40 years of age, but may occur at any age.

Reference
Wiki: Myasthenic syndrome

    Navajo neurohepatopathy (NNH) is an autosomal recessive disease that is prevalent among Navajo children in the southwestern United States. The major clinical features are hepatopathy, peripheral neuropathy, corneal anesthesia and scarring, acral mutilation, cerebral leukoencephalopathy, failure to thrive, and recurrent metabolic acidosis with intercurrent infections. Infantile, childhood, and classic forms of NNH have been described. Mitochondrial DNA (mtDNA) depletion was detected in the livers of two patients, suggesting a primary defect in mtDNA maintenance.

Reference
Pubmed: Navajo neurohepatopathy

    Hypotonia is a state of low muscle tone (the amount of tension or resistance to stretch in a muscle), often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength. Hypotonia is a lack of resistance to passive movement, whereas muscle weakness results in impaired active movement. Central hypotonia originates from the central nervous system, while peripheral hypotonia is related to problems within the spinal cord, peripheral nerves and/or skeletal muscles. Severe hypotonia in infancy is commonly known as floppy baby syndrome. Recognizing hypotonia, even in early infancy, is usually relatively straightforward, but diagnosing the underlying cause can be difficult and often unsuccessful. The long-term effects of hypotonia on a child's development and later life depend primarily on the severity of the muscle weakness and the nature of the cause. Some disorders have a specific treatment but the principal treatment for most hypotonia of idiopathic or neurologic cause is physical therapy and/or occupational therapy for remediation. Hypotonia is thought to be associated with the disruption of afferent input from stretch receptors and/or lack of the cerebellum¡¯s facilitatory efferent influence on the fusimotor system, the system that innervates intrafusal muscle fibers thereby controlling muscle spindle sensitivity. On examination a diminished resistance to passive movement will be noted and muscles may feel abnormally soft and limp on palpation. Diminished deep tendon reflexes also may be noted. Hypotonia is a condition that can be helped with early intervention.

Reference
Wiki: Neonatal hypotonia

    An autosomal dominant intellectual developmental disorder that has_material_basis_in an autosomal dominant mutation of the KIF1A gene on chromosome 2q37.3.

Reference
DiseaseOntology: NESCAV syndrome

    A physical disorder characterized by incomplete closure of the neural tube.

Reference
DiseaseOntology: Neural tube defect

    Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the head, neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the abdomen, neck, or chest, or a painless bluish lump under the skin. Typically, neuroblastoma occurs due to a genetic mutation occurring in the first trimester of pregnancy. Rarely, it may be due to a mutation inherited. Environmental factors have not been found to be involved. Diagnosis is based on a tissue biopsy. Occasionally, it may be found in a baby by ultrasound during pregnancy. At diagnosis, the cancer has usually already spread. The cancer is divided into low-, intermediate-, and high-risk groups based on a child's age, cancer stage, and what the cancer looks like. Treatment and outcomes depends on the risk group a person is in. Treatments may include observation, surgery, radiation, chemotherapy, or stem cell transplantation. Low-risk disease in babies typically has a good outcome with surgery or simply observation. In high-risk disease, chances of long-term survival, however, are less than 40%, despite aggressive treatment. Neuroblastoma is the most common cancer in babies and the third-most common cancer in children after leukemia and brain cancer. About one in every 7,000 children is affected at some time. About 90% of cases occur in children less than 5 years old, and it is rare in adults. Of cancer deaths in children, about 15% are due to neuroblastoma. The disease was first described in the 1800s.

Reference
Wiki: Neuroblastoma

    A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, tauopathies, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation.[2][3][4][5] Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies (like proteinopathy) and induced cell death.[6][7] These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well.

Reference
Wiki: Neurodegeneration

    Neurodegeneration with brain iron accumulation is a heterogenous group of inherited neurodegenerative diseases, still under research, in which iron accumulates in the basal ganglia, either resulting in progressive dystonia, parkinsonism, spasticity, optic atrophy, retinal degeneration, neuropsychiatric, or diverse neurologic abnormalities. Some of the NBIA disorders have also been associated with several genes in synapse and lipid metabolism related pathways. NBIA is not one disease but an entire group of disorders, characterized by an accumulation of brain iron, sometimes in the presence of axonal spheroids in the central nervous system. Iron accumulation can occur anywhere in the brain, with accumulation typically occurring in globus pallidus, substantia nigra, pars reticula, striatum and cerebellar dentate nuclei. Symptoms can include various movement disorders, neuropsychiatric issues, seizures, visual disturbances, and cognitive decline, usually in different combinations. Ten to fifteen genetic NBIA disorders involving various cell processes have been identified: iron metabolism, coenzyme A biosynthesis, phospholipid metabolism, ceramide metabolism, lysosomal disorders, as well as mutations in genes with unknown functions. Onset can occur at different ages, from early childhood to late adulthood. As of 2021 there were no curative treatments for any of the NBIA disorders, though several medications have been subject to clinical trial including the iron chelator deferiprone.

Reference
Wiki: Neurodegeneration with brain iron accumulation

    A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease, multiple system atrophy, tauopathies, and prion diseases. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic. Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assemblies (like proteinopathy) and induced cell death. These similarities suggest that therapeutic advances against one neurodegenerative disease might ameliorate other diseases as well. Within neurodegenerative diseases, it is estimated that 55 million people worldwide had dementia in 2019, and that by 2050 this figure will increase to 139 million people.

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Wiki: Neurodegenerative disease

    Neurodevelopmental disorders are a group of conditions that begin to emerge during childhood (or the development of the nervous system). According to the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (DSM-5) published in 2013, these conditions generally appear in early childhood, usually before children start school, and can persist into adulthood. The key characteristic of all these disorders is that they negatively impact a person's functioning in one or more domains of life (personal, social, academic, occupational) depending on the disorder and deficits it has caused. All of these disorders and their levels of impairment exist on a spectrum, and affected individuals can experience varying degrees of symptoms and deficits, despite having the same diagnosis. The DSM-5 classifies neurodevelopmental disorders into six overarching groups. Intellectual disability (intellectual development disorder) Communication disorders Autism spectrum disorder (ASD) Attention-deficit/hyperactivity disorder (ADHD) Neurodevelopmental motor disorders Specific learning disorders These disorders are commonly comorbid conditions, meaning that a person affected by one of these disorders will usually meet criteria for a second disorder.

Reference
Wiki: Neurodevelopmental abnormality

    Neurodevelopmental disorders are a group of conditions that begin to emerge during childhood (or the development of the nervous system). According to the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (DSM-5) published in 2013, these conditions generally appear in early childhood, usually before children start school, and can persist into adulthood.[1] The key characteristic of all these disorders is that they negatively impact a person's functioning in one or more domains of life (personal, social, academic, occupational) depending on the disorder and deficits it has caused. All of these disorders and their levels of impairment exist on a spectrum, and affected individuals can experience varying degrees of symptoms and deficits, despite having the same diagnosis.[1][2]

Reference
Wiki: Neurodevelopmental disorder

    Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. They most commonly occur in the intestine, where they are often called carcinoid tumors, but they are also found in the pancreas, lung, and the rest of the body. Although there are many kinds of NETs, they are treated as a group of tissue because the cells of these neoplasms share common features, including a similar histological appearance, having special secretory granules, and often producing biogenic amines and polypeptide hormones. The term "neuro" refers to the dense core granules (DCGs), similar to the DCGs in the serotonergic neurons storing monoamines. The term "endocrine" refers to the synthesis and secretion of these monoamines. The neuroendocrine system includes endocrine glands such as the pituitary, the parathyroids and the neuroendocrine adrenals, as well as endocrine islet tissue embedded within glandular tissue such as in the pancreas, and scattered cells in the exocrine parenchyma. The latter is known as the diffuse endocrine system.

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Wiki: Neuroendocrine cancer

    Neuroendocrine tumors (NETs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. They most commonly occur in the intestine, where they are often called carcinoid tumors, but they are also found in the pancreas, lung, and the rest of the body.

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Wiki: Neuroendocrine cancer/carcinoma

    An endocrine gland cancer that has_material_basis_in neuroendocrine cells.

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DiseaseOntology: Neuroendocrine tumor

    Neurofibromatosis (NF) refers to a group of three distinct genetic conditions in which tumors grow in the nervous system. The tumors are non-cancerous (benign) and often involve the skin or surrounding bone. Although symptoms are often mild, each condition presents differently. Neurofibromatosis type I (NF1) is typically characterized by caf¨¦ au lait spots (light-brown flat patches of skin), neurofibromas (small bumps in or under the skin), scoliosis (side-way curvature of the back), and headaches. Neurofibromatosis type II (NF2), on the other hand, may present with early-onset hearing loss, cataracts, tinnitus, difficulty walking or maintain balance, and muscle atrophy. The third type is called schwannomatosis and often presents in early adulthood with widespread pain, numbness, or tingling due to nerve compression. The cause is a genetic mutation in certain oncogenes. These can be inherited, or in about half of cases spontaneously occur during early development. Different mutations result in the three types of NF. Neurofibromatosis arise from the supporting cells of the nervous system rather than the neurons themselves. In NF1, the tumors are neurofibromas (tumors of the peripheral nerves), while in NF2 and schwannomatosis tumors of Schwann cells are more common. Diagnosis is typically based on symptoms, examination, medical imaging, and biopsy. Genetic testing may rarely be done to support the diagnosis. There is no known prevention or cure. Surgery may be done to remove tumors that are causing problems or have become cancerous. Radiation and chemotherapy may also be used if cancer occurs. A cochlear implant or auditory brainstem implant may help some who have hearing loss due to the condition. In the United States, about 1 in 3,500 people have NF1 and 1 in 25,000 have NF2. Males and females are affected equally often. In NF1, symptoms are often present at birth or develop before 10 years of age. While the condition typically worsens with time, most people with NF1 have a normal life expectancy. In NF2, symptoms may not become apparent until early adulthood. NF2 increases the risk of early death. Descriptions of the condition occur as far back as the 1st century. It was formally described by Friedrich Daniel von Recklinghausen in 1882, after whom it was previously named.

Reference
Wiki: Neurofibromatosis

    Neuroinflammation is inflammation of the nervous tissue. It may be initiated in response to a variety of cues, including infection, traumatic brain injury,[1] toxic metabolites, or autoimmunity.[2] In the central nervous system (CNS), including the brain and spinal cord, microglia are the resident innate immune cells that are activated in response to these cues.[2] The CNS is typically an immunologically privileged site because peripheral immune cells are generally blocked by the blood¨Cbrain barrier (BBB), a specialized structure composed of astrocytes and endothelial cells.[3] However, circulating peripheral immune cells may surpass a compromised BBB and encounter neurons and glial cells expressing major histocompatibility complex molecules, perpetuating the immune response.[4] Although the response is initiated to protect the central nervous system from the infectious agent, the effect may be toxic and widespread inflammation as well as further migration of leukocytes through the blood¨Cbrain barrier may occur.[2]

Reference
Wiki: Neuroinflammation

    Nerve injury is an injury to a nerve. There is no single classification system that can describe all the many variations of nerve injuries. In 1941, Seddon introduced a classification of nerve injuries based on three main types of nerve fiber injury and whether there is continuity of the nerve. Usually, however, nerve injuries are classified in five stages, based on the extent of damage to both the nerve and the surrounding connective tissue, since supporting glial cells may be involved. Unlike in the central nervous system, neuroregeneration in the peripheral nervous system is possible. The processes that occur in peripheral regeneration can be divided into the following major events: Wallerian degeneration, axon regeneration/growth, and reinnervation of nervous tissue. The events that occur in peripheral regeneration occur with respect to the axis of the nerve injury. The proximal stump refers to the end of the injured neuron that is still attached to the neuron cell body; it is the part that regenerates. The distal stump refers to the end of the injured neuron that is still attached to the end of the axon; it is the part of the neuron that will degenerate, but the stump remains capable of regenerating its axons. The study of nerve injury began during the American Civil War and greatly expanded during modern medicine with such advances as use of growth-promoting molecules.

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Wiki: Neurological damage

    A neuromuscular disease is any disease affecting the peripheral nervous system (PNS), the neuromuscular junctions, or skeletal muscles, all of which are components of the motor unit. Damage to any of these structures can cause muscle atrophy and weakness. Issues with sensation can also occur. Neuromuscular diseases can be acquired or genetic. Mutations of more than 650 genes have shown to be causes of neuromuscular diseases. Other causes include nerve or muscle degeneration, autoimmunity, toxins, medications, malnutrition, metabolic derangements, hormone imbalances, infection, nerve compression/entrapment, comprised blood supply, and trauma.

Reference
Wiki: Neuromuscular disorder

    Neuronal ceroid lipofuscinosis is the general name for a family of at least eight genetically separate neurodegenerative lysosomal storage diseases that result from excessive accumulation of lipopigments (lipofuscin) in the body's tissues. These lipopigments are made up of fats and proteins. Their name comes from the word stem "lipo-", which is a variation on lipid, and from the term "pigment", used because the substances take on a greenish-yellow color when viewed under an ultraviolet light microscope. These lipofuscin materials build up in neuronal cells and many organs, including the liver, spleen, myocardium, and kidneys.

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Wiki: Neuronal ceroid lipofuscinosis

    Angiocentric glioma (AG) refers to a rare neuroepithelial tumor when the superficial brain malignant cells enclose the brain vessels, commonly found in children and young adults. Initially identified in 2005 by Wang and his team from the University of Texas, AG was classified as Grade I by 2007 WHO Classification of Tumors of the Central Nervous System due to its benign clinical behavior, low proliferation index, and curative properties.[2] AG primarily affects children and young adults at an average initial diagnosis age of 16 years old. Over 85% AG patients experience intractable seizures since childhood, especially partial epilepsy.[3]

Reference
Wiki: Neuronal glioma

    Neuropathic pain is pain caused by a lesion or disease of the somatosensory nervous system.[2][3] Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous and/or episodic (paroxysmal) components. The latter resemble stabbings or electric shocks. Common qualities include burning or coldness, "pins and needles" sensations, numbness and itching.[3]

Reference
Wiki: Neuropathic pain

    Peripheral neuropathy, often shortened to neuropathy, refers to damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerve fibers are affected. Neuropathies affecting motor, sensory, or autonomic nerve fibers result in different symptoms. More than one type of fiber may be affected simultaneously. Peripheral neuropathy may be acute (with sudden onset, rapid progress) or chronic (symptoms begin subtly and progress slowly), and may be reversible or permanent. Common causes include systemic diseases (such as diabetes or leprosy), hyperglycemia-induced glycation, vitamin deficiency, medication (e.g., chemotherapy, or commonly prescribed antibiotics including metronidazole and the fluoroquinolone class of antibiotics (such as ciprofloxacin, levofloxacin, moxifloxacin)), traumatic injury, ischemia, radiation therapy, excessive alcohol consumption, immune system disease, celiac disease, non-celiac gluten sensitivity, or viral infection. It can also be genetic (present from birth) or idiopathic (no known cause). In conventional medical usage, the word neuropathy (neuro-, "nervous system" and -pathy, "disease of") without modifier usually means peripheral neuropathy. Neuropathy affecting just one nerve is called "mononeuropathy" and neuropathy involving nerves in roughly the same areas on both sides of the body is called "symmetrical polyneuropathy" or simply "polyneuropathy". When two or more (typically just a few, but sometimes many) separate nerves in disparate areas of the body are affected it is called "mononeuritis multiplex", "multifocal mononeuropathy", or "multiple mononeuropathy". Neuropathy may cause painful cramps, fasciculations (fine muscle twitching), muscle loss, bone degeneration, and changes in the skin, hair, and nails. Additionally, motor neuropathy may cause impaired balance and coordination or, most commonly, muscle weakness; sensory neuropathy may cause numbness to touch and vibration, reduced position sense causing poorer coordination and balance, reduced sensitivity to temperature change and pain, spontaneous tingling or burning pain, or allodynia (pain from normally nonpainful stimuli, such as light touch); and autonomic neuropathy may produce diverse symptoms, depending on the affected glands and organs, but common symptoms are poor bladder control, abnormal blood pressure or heart rate, and reduced ability to sweat normally.

Reference
Wiki: Neuropathy

    Oculogastrointestinal neurodevelopmental syndrome (OGIN) is characterized by microphthalmia and/or coloboma in association with other congenital anomalies, including imperforate anus, horseshoe kidney, and structural cardiac defects. Hearing loss and severe developmental delay are also observed in most patients (Zha et al., 2020; Mor-Shaked et al., 2021).

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OMIM: Oculogastrointestinal neurodevelopmental syndrome

    Okur-Chung neurodevelopmental syndrome (OCNDS) is characterized by delayed psychomotor development, intellectual disability with poor speech, behavioral abnormalities, cortical malformations in some patients, and variable dysmorphic facial features. Additional features, including microcephaly, gastrointestinal problems, and low levels of immunoglobulins, may be observed in some patients (Okur et al., 2016).

Reference
OMIM: Okur-chung neurodevelopmental syndrome

    Oligodendrogliomas are a type of glioma that are believed to originate from the oligodendrocytes of the brain or from a glial precursor cell. They occur primarily in adults (9.4% of all primary brain and central nervous system tumors) but are also found in children (4% of all primary brain tumors).

Reference
Wiki: Oligodendroglioma

    Paramyotonia congenita (PC) is a rare congenital autosomal dominant neuromuscular disorder characterized by "paradoxical" myotonia.[2] This type of myotonia has been termed paradoxical because it becomes worse with exercise whereas classical myotonia, as seen in myotonia congenita, is alleviated by exercise. PC is also distinguished as it can be induced by cold temperatures. Although more typical of the periodic paralytic disorders, patients with PC may also have potassium-provoked paralysis. PC typically presents within the first decade of life and has 100% penetrance. Patients with this disorder commonly present with myotonia in the face or upper extremities. The lower extremities are generally less affected. While some other related disorders result in muscle atrophy, this is not normally the case with PC. This disease can also present as hyperkalemic periodic paralysis and there is debate as to whether the two disorders are actually distinct.[3]

Reference
Wiki: Paramyotonia congenita

    Paraplegia, or paraparesis, is an impairment in motor or sensory function of the lower extremities. The word comes from Ionic Greek (¦Ð¦Á¦Ñ¦Á¦Ð¦Ë¦Ç¦Ã?¦Ç) "half-stricken".[citation needed] It is usually caused by spinal cord injury or a congenital condition that affects the neural (brain) elements of the spinal canal. The area of the spinal canal that is affected in paraplegia is either the thoracic, lumbar, or sacral regions. If four limbs are affected by paralysis, tetraplegia or quadriplegia is the correct term. If only one limb is affected, the correct term is monoplegia. Spastic paraplegia is a form of paraplegia defined by spasticity of the affected muscles, rather than flaccid paralysis.

Reference
Wiki: Paraplegia

    The paroxysmal dyskinesias (PD) are a group of movement disorders characterized by attacks of hyperkinesia with intact consciousness. Paroxysmal dyskinesia is a rare disorder, however the number of individuals it affects remains unclear. There are three different subtypes of PD that include paroxysmal kinesigenic dyskinesia (PKD), paroxysmal nonkinesigenic dyskinesia (PNKD), and paroxysmal exercise-induced dyskinesia (PED). Other neurological diseases have similar symptoms to PD, such as epilepsy and Parkinson's. The different subtypes make accurate and quick diagnosis of PD challenging. Thus, PD is often under reported and misdiagnosed, making it difficult to accurately study its prevalence in human populations. Onset of PD is usually in late childhood to early adolescence. New drug regimens help treat symptoms of PD, but no cure for the disorder is known.

Reference
Wiki: Paroxysmal kinesigenic dyskinesia

    The paroxysmal dyskinesias (PD) are a group of movement disorders characterized by attacks of hyperkinesia with intact consciousness. Paroxysmal dyskinesia is a rare disorder, however the number of individuals it affects remains unclear. There are three different subtypes of PD that include paroxysmal kinesigenic dyskinesia (PKD), paroxysmal nonkinesigenic dyskinesia (PNKD), and paroxysmal exercise-induced dyskinesia (PED). Other neurological diseases have similar symptoms to PD, such as epilepsy and Parkinson's. The different subtypes make accurate and quick diagnosis of PD challenging. Thus, PD is often under reported and misdiagnosed, making it difficult to accurately study its prevalence in human populations. Onset of PD is usually in late childhood to early adolescence. New drug regimens help treat symptoms of PD, but no cure for the disorder is known.

Reference
Wiki: Paroxysmal nonkinesigenic dyskinesia

    Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder and is characterized by recurrent episodes of complete or partial obstruction of the upper airway leading to reduced or absent breathing during sleep. These episodes are termed "apneas" with complete or near-complete cessation of breathing, or "hypopneas" when the reduction in breathing is partial. In either case, a fall in blood oxygen saturation, a disruption in sleep, or both, may result. A high frequency of apneas or hypopneas during sleep may interfere with the quality of sleep, which ¨C in combination with disturbances in blood oxygenation ¨C is thought to contribute to negative consequences to health and quality of life.[1] The terms obstructive sleep apnea syndrome (OSAS) or obstructive sleep apnea¨Chypopnea syndrome (OSAHS) may be used to refer to OSA when it is associated with symptoms during the daytime (e.g. excessive daytime sleepiness, decreased cognitive function).[2][3]

Reference
Wiki: Perioperative neurocognitive disorder

    PCWH syndrome is a complex neurocristopathy that includes features of 4 distinct syndromes: peripheral demyelinating neuropathy (see 118200), central dysmyelination, Waardenburg syndrome, and Hirschsprung disease (see 142623) (Inoue et al., 2004). Inoue et al. (2004) proposed the acronym PCWH for this disorder.

Reference
OMIM: Peripheral demyelinating neuropathy

    Peripheral neuropathy, often shortened to neuropathy, refers to damage or disease affecting the nerves.[1] Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerve fibers are affected. Neuropathies affecting motor, sensory, or autonomic nerve fibers result in different symptoms. More than one type of fiber may be affected simultaneously. Peripheral neuropathy may be acute (with sudden onset, rapid progress) or chronic (symptoms begin subtly and progress slowly), and may be reversible or permanent.

Reference
Wiki: Peripheral neuropathy

    Peripheral neuropathy with variable spasticity, exercise intolerance, and developmental delay (PNSED) is an autosomal recessive multisystemic disorder with highly variable manifestations, even within the same family. Some patients present in infancy with hypotonia and global developmental delay with poor or absent motor skill acquisition and poor growth, whereas others present as young adults with exercise intolerance and muscle weakness. All patients have signs of a peripheral neuropathy, usually demyelinating, with distal muscle weakness and atrophy and distal sensory impairment; many become wheelchair-bound. Additional features include spasticity, extensor plantar responses, contractures, cerebellar signs, seizures, short stature, and rare involvement of other organ systems, including the heart, pancreas, and kidney. Biochemical analysis may show deficiencies in mitochondrial respiratory complex enzyme activities in patient tissue, although this is not always apparent. Lactate is frequently increased, suggesting mitochondrial dysfunction (Powell et al., 2015; Argente-Escrig et al., 2022).

Reference
OMIM: Peripheral neuropathy with variable spasticity

    Pheochromocytoma is a rare tumor of the adrenal medulla composed of chromaffin cells, also known as pheochromocytes. When a tumor composed of the same cells as a pheochromocytoma develops outside the adrenal gland, it is referred to as a paraganglioma. These neuroendocrine tumors typically release massive amounts of catecholamines which result in the most common symptoms, including hypertension (high blood pressure), tachycardia (fast heart rate), and sweating. Rarely, some tumors (especially paragangliomas) may secrete little to no catecholamines, making diagnosis difficult. While tumors of the head and neck are parasympathetic, their sympathetic counterparts are predominantly located in the abdomen and pelvis, particularly concentrated at the organ of Zuckerkandl.

Reference
Wiki: Pheochromocytoma and Paraganglioma

    An autosomal dominant intellectual developmental disorder that is characterized by distinctive facial characteristics, especially when smiling, plantar fat pads, and other limb anomalies and that has_material_basis_in heterozygous mutation in the TBL1XR1 gene on chromosome 3q26.

Reference
DiseaseOntology: Pierpont syndrome

    Poirier-Bienvenu neurodevelopmental syndrome (POBINDS) is a neurologic disorder characterized in most cases by early-onset seizures and variably impaired intellectual development (ID). The severity of neurologic impairment is highly variable: some patients may have refractory seizures and be bedridden with no meaningful speech, whereas others may have treatment-responsive seizures and achieve normal psychomotor development (summary by Li et al., 2019).

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OMIM: Poirier-Bienvenu neurodevelopmental syndrome

    A peripheral system disease that is characterized by damage affecting peripheral nerves (peripheral neuropathy) in roughly the same areas on both sides of the body, featuring weakness, numbness, pins-and-needles, and burning pain.

Reference
DiseaseOntology: Polyneuropathy

    Pontocerebellar hypoplasia (PCH) is a heterogeneous group of rare neurodegenerative disorders caused by genetic mutations and characterised by progressive atrophy of various parts of the brain such as the cerebellum or brainstem (particularly the pons). Where known, these disorders are inherited in an autosomal recessive fashion. There is no known cure for PCH.

Reference
Wiki: Pontocerebellar hypoplasia

    Postherpetic neuralgia (PHN) is neuropathic pain that occurs due to damage to a peripheral nerve caused by the reactivation of the varicella zoster virus (herpes zoster, also known as shingles). PHN is defined as pain in a dermatomal distribution that lasts for at least 90 days after an outbreak of herpes zoster. Several types of pain may occur with PHN including continuous burning pain, episodes of severe shooting or electric-like pain, and a heightened sensitivity to gentle touch which would not otherwise cause pain or to painful stimuli. Abnormal sensations and itching may also occur. Postherpetic neuralgia is the most common long-term complication of herpes zoster, and occurs in approximately 20% of patients with shingles. Risk factors for PHN include older age, severe prodrome or rash, severe acute zoster pain, ophthalmic involvement, immunosuppression, and chronic conditions such as diabetes mellitus and lupus. The pain from postherpetic neuralgia can be very severe and debilitating. There is no treatment which modifies the course of the disease and management primarily aims to control symptoms. Affected individuals often experience a decrease in their quality of life. Shingles vaccination is the only way for adults to be protected against both shingles and postherpetic neuralgia, with the vaccine Shingrix providing 90% protection from postherpetic neuralgia. The chickenpox vaccine is approved for infants to prevent chickenpox, which also protects against PHN from a herpes zoster infection.

Reference
Wiki: Postherpetic neuralgia

    Primitive neuroectodermal tumor is a malignant (cancerous) neural crest tumor. It is a rare tumor, usually occurring in children and young adults under 25 years of age. The overall 5 year survival rate is about 53%. It gets its name because the majority of the cells in the tumor are derived from neuroectoderm, but have not developed and differentiated in the way a normal neuron would, and so the cells appear "primitive". PNET belongs to the Ewing family of tumors.

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Wiki: Primitive neuroectodermal tumor

    Progressive Myoclonic Epilepsies (PME) are a rare group of inherited neurodegenerative diseases characterized by myoclonus, resistance to treatment, and neurological deterioration. The cause of PME depends largely on the type of PME. Most PMEs are caused by autosomal dominant or recessive and mitochondrial mutations. The location of the mutation also affects the inheritance and treatment of PME. Diagnosing PME is difficult due to their genetic heterogeneity and the lack of a genetic mutation identified in some patients. The prognosis depends largely on the worsening symptoms and failure to respond to treatment. There is no current cure for PME and treatment focuses on managing myoclonus and seizures through antiepileptic medication (AED). The age of onset depends on the specific PME but PME can affect people of all ages. In Unverricht-Lundborg disease (ULD) the age of onset is between 6¨C15 years, while in Adult Neuronal ceroid lipofuscinoses (Adult NCL) the age of onset can be as late as 30. Symptoms often include action or stimuli induced myoclonus, seizures, neuropathy, cognitive decline, and spike and wave or no cerebral discharges. The prognosis of those diagnosed with PME is poor. The person often becomes reliant on a wheelchair, enters a vegetative state due to myoclonus, and has a shortened life expectancy.

Reference
Wiki: Progressive myoclonus epilepsy

    Progressive supranuclear palsy (PSP) is a late-onset neurodegenerative disease involving the gradual deterioration and death of specific volumes of the brain. The condition leads to symptoms including loss of balance, slowing of movement, difficulty moving the eyes, and cognitive impairment. PSP may be mistaken for other types of neurodegeneration such as Parkinson's disease, frontotemporal dementia and Alzheimer's disease. The cause of the condition is uncertain, but involves the accumulation of tau protein within the brain. Medications such as levodopa and amantadine may be useful in some cases. PSP affects about six people per 100,000. The first symptoms typically occur at 60¨C70 years of age. Males are slightly more likely to be affected than females. No association has been found between PSP and any particular race, location, or occupation.

Reference
Wiki: Progressive superanuclear palsy

    Progressive supranuclear palsy (PSP) is a late-onset neurodegenerative disease involving the gradual deterioration and death of specific volumes of the brain. The condition leads to symptoms including loss of balance, slowing of movement, difficulty moving the eyes, and cognitive impairment. PSP may be mistaken for other types of neurodegeneration such as Parkinson's disease, frontotemporal dementia and Alzheimer's disease. The cause of the condition is uncertain, but involves the accumulation of tau protein within the brain. Medications such as levodopa and amantadine may be useful in some cases. PSP affects about six people per 100,000. The first symptoms typically occur at 60¨C70 years of age. Males are slightly more likely to be affected than females. No association has been found between PSP and any particular race, location, or occupation.

Reference
Wiki: Progressive supranuclear ophthalmoplegia

    Progressive supranuclear palsy (PSP) is a late-onset neurodegenerative disease involving the gradual deterioration and death of specific volumes of the brain. The condition leads to symptoms including loss of balance, slowing of movement, difficulty moving the eyes, and cognitive impairment. PSP may be mistaken for other types of neurodegeneration such as Parkinson's disease, frontotemporal dementia and Alzheimer's disease. The cause of the condition is uncertain, but involves the accumulation of tau protein within the brain. Medications such as levodopa and amantadine may be useful in some cases. PSP affects about six people per 100,000. The first symptoms typically occur at 60¨C70 years of age. Males are slightly more likely to be affected than females. No association has been found between PSP and any particular race, location, or occupation.

Reference
Wiki: Progressive supranuclear palsy

    Pyridoxine-dependent epilepsy (PDE) is a rare genetic disorder characterized by intractable seizures in the prenatal and neonatal period. The disorder was first recognized in the 1950s, with the first description provided by Hunt et al. in 1954. More recently, pathogenic variants within the ALDH7A1 gene have been identified to cause PDE.

Reference
Wiki: Pyridoxine-dependent epilepsy

    Hatano et al. (2004) reported 8 unrelated families with autosomal recessive PD from various regions in Asia that showed linkage to the PARK6 locus. Five families were consanguineous. Age at onset ranged from 18 to 56 years, although most had onset in the third or fourth decades. The main clinical features included rigidity, bradykinesia, asymmetric onset, postural instability, and favorable response to levodopa. Other variable features included resting tremor, frozen gait, sleep benefit, dystonia at onset (in 2 patients), hyperreflexia, and levodopa-induced dyskinesias. Progression was generally slow.

Reference
OMIM: Recessive parkinson disease

    A pervasive developmental disease that is characterized by normal early growth and development followed by a slowing of development, loss of purposeful use of the hands, distinctive hand movements, slowed brain and head growth, problems with walking, seizures, and intellectual disability.

Reference
DiseaseOntology: Rett syndrome

    A neurological examination is the assessment of sensory neuron and motor responses, especially reflexes, to determine whether the nervous system is impaired. This typically includes a physical examination and a review of the patient's medical history, but not deeper investigation such as neuroimaging. It can be used both as a screening tool and as an investigative tool, the former of which when examining the patient when there is no expected neurological deficit and the latter of which when examining a patient where you do expect to find abnormalities. If a problem is found either in an investigative or screening process, then further tests can be carried out to focus on a particular aspect of the nervous system (such as lumbar punctures and blood tests). In general, a neurological examination is focused on finding out whether there are lesions in the central and peripheral nervous systems or there is another diffuse process that is troubling the patient. Once the patient has been thoroughly tested, it is then the role of the physician to determine whether these findings combine to form a recognizable medical syndrome or neurological disorder such as Parkinson's disease or motor neurone disease. Finally, it is the role of the physician to find the cause for why such a problem has occurred, for example finding whether the problem is due to inflammation or is congenital.

Reference
Wiki: Rigidity and multifocal seizure syndrome

    Schizophrenia is a mental disorder characterized by reoccurring episodes of psychosis that are correlated with a general misperception of reality. Other common signs include hallucinations (typically hearing voices), delusions (i.e., paranoia), disorganized thinking, social withdrawal, and flat affect. Symptoms develop gradually and typically begin during young adulthood and are never resolved. There is no objective diagnostic test; diagnosis is based on observed behavior, a psychiatric history that includes the person's reported experiences, and reports of others familiar with the person. For a diagnosis of schizophrenia, the described symptoms need to have been present for at least six months (according to the DSM-5) or one month (according to the ICD-11). Many people with schizophrenia have other mental disorders, especially substance use disorders, depressive disorders, anxiety disorders, and obsessive¨Ccompulsive disorder. About 0.3% to 0.7% of people are diagnosed with schizophrenia during their lifetime. In 2017, there were an estimated 1.1 million new cases and in 2022 a total of 24 million cases globally. Males are more often affected and on average have an earlier onset than females. The causes of schizophrenia may include genetic and environmental factors. Genetic factors include a variety of common and rare genetic variants. Possible environmental factors include being raised in a city, childhood adversity, cannabis use during adolescence, infections, the age of a person's mother or father, and poor nutrition during pregnancy. About half of those diagnosed with schizophrenia will have a significant improvement over the long term with no further relapses, and a small proportion of these will recover completely. The other half will have a lifelong impairment. In severe cases, people may be admitted to hospitals. Social problems such as long-term unemployment, poverty, homelessness, exploitation and victimization are commonly correlated with schizophrenia. Compared to the general population, people with schizophrenia have a higher suicide rate (about 5% overall) and more physical health problems, leading to an average decrease in life expectancy by 20 to 28 years. In 2015, an estimated 17,000 deaths were linked to schizophrenia. The mainstay of treatment is antipsychotic medication, including olanzapine and risperidone, along with counseling, job training and social rehabilitation. Up to a third of people do not respond to initial antipsychotics, in which case clozapine gained approval by the US Food and Drug Administration for treatment-resistant cases. In a network comparative meta-analysis of 15 antipsychotic drugs, clozapine was significantly more effective than all other drugs, although clozapine's heavily multimodal action may cause more significant side effects. In situations where doctors judge that there is a risk of harm to self or others, they may impose short involuntary hospitalization. Long-term hospitalization is used on a small number of people with severe schizophrenia. In some countries where supportive services are limited or unavailable, long-term hospital stays are more common.

Reference
Wiki: Schizophrenia

    A schwannoma (or neurilemmoma) is a usually benign nerve sheath tumor composed of Schwann cells, which normally produce the insulating myelin sheath covering peripheral nerves. Schwannomas are homogeneous tumors, consisting only of Schwann cells. The tumor cells always stay on the outside of the nerve, but the tumor itself may either push the nerve aside and/or up against a bony structure (thereby possibly causing damage). Schwannomas are relatively slow-growing. For reasons not yet understood, schwannomas are mostly benign and less than 1% become malignant, degenerating into a form of cancer known as neurofibrosarcoma. These masses are generally contained within a capsule, so surgical removal is often successful.[3]

Reference
Wiki: Schwannoma

    A seizure is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain.[6] Outward effects vary from uncontrolled shaking movements involving much of the body with loss of consciousness (tonic-clonic seizure), to shaking movements involving only part of the body with variable levels of consciousness (focal seizure), to a subtle momentary loss of awareness (absence seizure).[3] These episodes usually last less than two minutes and it takes some time to return to normal.[5][8] Loss of bladder control may occur.[3]

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Wiki: Seizures

    Dravet syndrome (DS), previously known as severe myoclonic epilepsy of infancy (SMEI), is an autosomal dominant genetic disorder which causes a catastrophic form of epilepsy, with prolonged seizures that are often triggered by hot temperatures or fever. It is very difficult to treat with anticonvulsant medications. It often begins before one year of age, with six months being the age that seizures, char-ac-ter-ized by prolonged convulsions and triggered by fever, usually begin. Seizures are the most common form of DS. DS is diagnosed clinically and genetic testing is recommended if there is any doubt. Due to drug-refractory epilepsy in DS, many other therapies are being explored to prolong the life expectancy of patients.

Reference
Wiki: Severe myoclonic epilepsy

    X-linked myotubular myopathy (MTM) is a form of centronuclear myopathy (CNM) associated with mutations in the myotubularin 1 gene. It is found almost always in male infants. It is one of the severest congenital muscle diseases and is characterized by marked muscle weakness, hypotonia and feeding and breathing difficulties.

Reference
Wiki: Severe X-linked myotubular myopathy

    A syndrome characterized by global developmental delay, variably impaired intellectual development, variable dysmorphic features, and behavioral abnormalities, including autism spectrum disorder and ADHD that has_material_basis_in hemizygous mutation in the BCORL1 gene on chromosome Xq26.1.

Reference
DiseaseOntology: Shukla-Vernon syndrome

    Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive gait disorder. The disease presents with progressive stiffness (spasticity) and contraction in the lower limbs. HSP is also known as hereditary spastic paraparesis, familial spastic paraplegia, French settlement disease, Strumpell disease, or Strumpell-Lorrain disease. The symptoms are a result of dysfunction of long axons in the spinal cord. The affected cells are the primary motor neurons; therefore, the disease is an upper motor neuron disease. HSP is not a form of cerebral palsy even though it physically may appear and behave much the same as spastic diplegia. The origin of HSP is different from cerebral palsy. Despite this, some of the same anti-spasticity medications used in spastic cerebral palsy are sometimes used to treat HSP symptoms. HSP is caused by defects in transport of proteins, structural proteins, cell-maintaining proteins, lipids, and other substances through the cell. Long nerve fibers (axons) are affected because long distances make nerve cells particularly sensitive to defects in these mentioned mechanisms. The disease was first described in 1880 by the German neurologist Adolph Str¨¹mpell. It was described more extensively in 1888 by Maurice Lorrain, a French physician. Due to their contribution in describing the disease, it is still called Str¨¹mpell-Lorrain disease in French-speaking countries. The term hereditary spastic paraplegia was coined by Anita Harding in 1983.

Reference
Wiki: Spastic paraplegia

    Spinal muscular atrophy (SMA) is a rare neuromuscular disorder that results in the loss of motor neurons and progressive muscle wasting. It is usually diagnosed in infancy or early childhood and if left untreated it is the most common genetic cause of infant death. It may also appear later in life and then have a milder course of the disease. The common feature is progressive weakness of voluntary muscles, with arm, leg and respiratory muscles being affected first. Associated problems may include poor head control, difficulties swallowing, scoliosis, and joint contractures. The age of onset and the severity of symptoms form the basis of the traditional classification of spinal muscular atrophy into a number of types. Spinal muscular atrophy is due to an abnormality (mutation) in the SMN1 gene which encodes SMN, a protein necessary for survival of motor neurons. Loss of these neurons in the spinal cord prevents signalling between the brain and skeletal muscles. Another gene, SMN2, is considered a disease modifying gene, since usually the more the SMN2 copies, the milder is the disease course. The diagnosis of SMA is based on symptoms and confirmed by genetic testing. Usually, the mutation in the SMN1 gene is inherited from both parents in an autosomal recessive manner, although in around 2% of cases it occurs during early development (de novo). The incidence of spinal muscular atrophy worldwide varies from about 1 in 4,000 births to around 1 in 16,000 births, with 1 in 7,000 and 1 in 10,000 commonly quoted for Europe and the US respectively. Outcomes in the natural course of the disease vary from death within a few weeks after birth in the most acute cases to normal life expectancy in the protracted SMA forms. The introduction of causative treatments in 2016 has significantly improved the outcomes. Medications that target the genetic cause of the disease include nusinersen, risdiplam, and the gene therapy medication onasemnogene abeparvovec. Supportive care includes physical therapy, occupational therapy, respiratory support, nutritional support, orthopaedic interventions, and mobility support.

Reference
Wiki: Spinal muscular atrophy

    Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens,[2] and is the cause of 60¨C70% of cases of dementia.[2][15] The most common early symptom is difficulty in remembering recent events.[1] As the disease advances, symptoms can include problems with language, disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and behavioral issues.[2] As a person's condition declines, they often withdraw from family and society.[16] Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the average life expectancy following diagnosis is three to twelve years.[11][12][13]

Reference
Wiki: Sporadic alzheimer disease

    A fetal alcohol spectrum disorder that results in central nervous system dysfunction and behavioral and/or cognitive deficits due to prenatal alcohol exposure.

Reference
DiseaseOntology: STAG1-related disorder

    A congenital nervous system abnormality characterized by migration of neurons to ectopic locations in the brain where the neurons form areas that appear as band-like clusters of white tissue underneath the gray tissue of the cerebral cortex.

Reference
DiseaseOntology: subcortical band heterotopia

    An intellectual disability that is characterized by the presence of associated medical and behavioral sign and symptoms.

Reference
DiseaseOntology: Syndromic intellectual disability

    Synucleinopathies (also called ¦Á-Synucleinopathies) are neurodegenerative diseases characterised by the abnormal accumulation of aggregates of alpha-synuclein protein in neurons, nerve fibres or glial cells. There are three main types of synucleinopathy: Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Other rare disorders, such as various neuroaxonal dystrophies, also have ¦Á-synuclein pathologies. Additionally, autopsy studies have shown that around 6% of sporadic Alzheimer's Disease exhibit ¦Á-synuclein positive Lewy pathology, and are sub-classed as Alzheimer's Disease with Amygdalar Restricted Lewy Bodies (AD/ALB).

Reference
Wiki: Synucleinopathy

    Tatton-Brown¨CRahman syndrome (TBRS) is a rare overgrowth and intellectual disability syndrome caused by autosomal dominant mutations in the DNMT3A gene. The syndrome was first recognized in 2014 by Katrina Tatton-Brown, Nazneen Rahman, and collaborators.

Reference
Wiki: Tatton-Brown-rahman syndrome

    A GM2 gangliosidosis that is characterized onset in infancy of developmental retardation, followed by paralysis, dementia and blindness, with death in the second or third year of life and has_material_basis_in homozygous or compound heterozygous mutation in the alpha subunit of the hexosaminidase A gene (HEXA) on chromosome 15q23.

Reference
DiseaseOntology: Tay-sachs disease

    A syndrome characterized by variable craniofacial dysmorphism, ocular coloboma, seizures, and brain abnormalities including partial or complete absence of the corpus callosum that has_material_basis_in [zygosity of] mutation in the C12ORF57 gene on chromosome 12p13.31.

Reference
DiseaseOntology: Temtamy syndrome

    An amyloidosis that is characterized by a loss of sensation in the extremities, cardiomyopathy, nephropathy, vitreous opacities, and CNS amyloidosis resulting from abnormal deposits of amyloid protein in the body's organs and tissues and has_material_basis_in autosomal dominant inheritance of mutations in the TTR gene.

Reference
DiseaseOntology: Transthyretin amyloidosis

    Hereditary spastic paraplegia (HSP) is a group of inherited diseases whose main feature is a progressive gait disorder. The disease presents with progressive stiffness (spasticity) and contraction in the lower limbs. HSP is also known as hereditary spastic paraparesis, familial spastic paraplegia, French settlement disease, Strumpell disease, or Strumpell-Lorrain disease. The symptoms are a result of dysfunction of long axons in the spinal cord. The affected cells are the primary motor neurons; therefore, the disease is an upper motor neuron disease. HSP is not a form of cerebral palsy even though it physically may appear and behave much the same as spastic diplegia. The origin of HSP is different from cerebral palsy. Despite this, some of the same anti-spasticity medications used in spastic cerebral palsy are sometimes used to treat HSP symptoms. HSP is caused by defects in transport of proteins, structural proteins, cell-maintaining proteins, lipids, and other substances through the cell. Long nerve fibers (axons) are affected because long distances make nerve cells particularly sensitive to defects in these mentioned mechanisms. The disease was first described in 1880 by the German neurologist Adolph Str¨¹mpell. It was described more extensively in 1888 by Maurice Lorrain, a French physician. Due to their contribution in describing the disease, it is still called Str¨¹mpell-Lorrain disease in French-speaking countries. The term hereditary spastic paraplegia was coined by Anita Harding in 1983.

Reference
Wiki: Troyer syndrome

    A vestibular schwannoma (VS), also called acoustic neuroma, is a benign tumor that develops on the vestibulocochlear nerve that passes from the inner ear to the brain. The tumor originates when Schwann cells that form the insulating myelin sheath on the nerve malfunction. Normally, Schwann cells function beneficially to protect the nerves which transmit balance and sound information to the brain. However, sometimes a mutation in the tumor suppressor gene, NF2, located on chromosome 22, results in abnormal production of the cell protein named Merlin, and Schwann cells multiply to form a tumor. The tumor originates mostly on the vestibular division of the nerve rather than the cochlear division, but hearing as well as balance will be affected as the tumor enlarges. The great majority of these VSs (95%) are unilateral, in one ear only. They are called "sporadic" (i.e., by-chance, non-hereditary). Although non-cancerous, they can do harm or even become life-threatening if they grow to press on other cranial nerves and vital structures such as the brainstem. Variations in the mutation determine the nature of the tumor's development. The only environmental exposure that has been definitely associated with the growth of a VS is therapeutic radiation exposure to the head.

Reference
Wiki: Vestibular schwannomas

    Autosomal recessive familial visceral neuropathy-1 (VSCN1) is characterized by a broad spectrum of developmental anomalies associating neural crest and extraneural crest features, including intestinal dysmotility due to aganglionosis (Hirschsprung disease), hypoganglionosis, and/or chronic intestinal pseudoobstruction. Some patients develop progressive peripheral neuropathy, and arthrogryposis has been observed. Hypoplasia or aplasia of the olfactory bulb and of the external auditory canals, as well as microtia or anotia, have been reported. Patients also exhibit facial dysmorphisms, including microretrognathia in most; other variable features include structural cardiac anomalies and arthrogryposis with multiple pterygia (Le et al., 2021).

Reference
OMIM: Visceral neuropathy

    Wolfram-like syndrome is a rare autosomal dominant genetic disorder that shares some of the features shown by those affected with the autosomal recessive Wolfram syndrome. It is a type of WFS1-related disorder.

Reference
Wiki: Wolfram-like syndrome

    X-linked intellectual disability refers to medical disorders associated with X-linked recessive inheritance that result in intellectual disability. As with most X-linked disorders, males are more heavily affected than females. Females with one affected X chromosome and one normal X chromosome tend to have milder symptoms. Unlike many other types of intellectual disability, the genetics of these conditions are relatively well understood. It has been estimated there are ~200 genes involved in this syndrome; of these ~100 have been identified. Many of these genes are found on the short 'p' arm of the chromosome, and duplications at Xp11.2 are associated with the syndromic form of the condition. X-linked intellectual disability accounts for ~16% of all cases of intellectual disability in males.

Reference
Wiki: X-linked intellectual disability

    Xia-Gibbs syndrome, is genetic disorder caused by a heterozygous mutation in the AHDC1 gene (AT hook, DNA binding motif, containing 1) on chromosome 1p36 . Around 300 cases worldwide to this date (September 23, 2022) have been diagnosed.

Reference
Wiki: Xia-Gibbs syndrome

    A syndrome characterized by onset in the first decade of highly variable neurodevelopmental phenotypes including global developmental delay, intellectual disability, seizures, hearing and visual problems, and ataxia that has_material_basis_in homozygous or compound heterozygous mutation in the OGDHL gene on chromosome 10q11.23.

Reference
DiseaseOntology: Yoon-Bellen neurodevelopmental syndrome