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Dystonia

MedGen UID:
504804
Concept ID:
CN001220
Finding
Synonyms: Dystonic disease; Dystonic movements
 
HPO: HP:0001332

Definition

An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk. [from HPO]

Conditions with this feature

Ataxia-telangiectasia syndrome
MedGen UID:
439
Concept ID:
C0004135
Congenital Abnormality
Ataxia-telangiectasia (AT) is an autosomal recessive disorder characterized by cerebellar ataxia, telangiectases, immune defects, and a predisposition to malignancy. Chromosomal breakage is a feature. AT cells are abnormally sensitive to killing by ionizing radiation (IR), and abnormally resistant to inhibition of DNA synthesis by ionizing radiation. The latter trait has been used to identify complementation groups for the classic form of the disease (Jaspers et al., 1988). At least 4 of these (A, C, D, and E) map to chromosome 11q23 (Sanal et al., 1990) and are associated with mutations in the ATM gene.
Wilson's disease
MedGen UID:
42426
Concept ID:
C0019202
Disease or Syndrome
Wilson disease is a disorder of copper metabolism that can present with hepatic, neurologic, or psychiatric disturbances, or a combination of these, in individuals ranging from age three years to over 50 years; symptoms vary among and within families. Liver disease includes recurrent jaundice, simple acute self-limited hepatitis-like illness, autoimmune-type hepatitis, fulminant hepatic failure, or chronic liver disease. Neurologic presentations include movement disorders (tremors, poor coordination, loss of fine-motor control, chorea, choreoathetosis) or rigid dystonia (mask-like facies, rigidity, gait disturbance, pseudobulbar involvement). Psychiatric disturbance includes depression, neurotic behaviors, disorganization of personality, and, occasionally, intellectual deterioration. Kayser-Fleischer rings, frequently present, result from copper deposition in Descemet's membrane of the cornea and reflect a high degree of copper storage in the body.
Leigh's disease
MedGen UID:
44095
Concept ID:
C0023264
Disease or Syndrome
Leigh syndrome is an early-onset progressive neurodegenerative disorder with a characteristic neuropathology consisting of focal, bilateral lesions in one or more areas of the central nervous system, including the brainstem, thalamus, basal ganglia, cerebellum, and spinal cord. The lesions are areas of demyelination, gliosis, necrosis, spongiosis, or capillary proliferation. Clinical symptoms depend on which areas of the central nervous system are involved. The most common underlying cause is a defect in oxidative phosphorylation (Dahl, 1998). Leigh syndrome may be a feature of a deficiency of any of the mitochondrial respiratory chain complexes: complex I deficiency (252010), complex II deficiency (252011), complex III deficiency (124000), complex IV deficiency (cytochrome c oxidase; 220110), or complex V deficiency (604273).
Lesch-Nyhan syndrome
MedGen UID:
9721
Concept ID:
C0023374
Disease or Syndrome
Lesch-Nyhan syndrome is characterized by motor dysfunction that resembles cerebral palsy, cognitive and behavioral disturbances, and uric acid overproduction (hyperuricemia). The most common presenting features, hypotonia and developmental delay, are evident by age three to six months. Affected children are delayed in sitting and most never walk. Within the first few years, extrapyramidal involvement (e.g., dystonia, choreoathetosis, opisthotonos) and pyramidal involvement (e.g., spasticity, hyperreflexia, extensor plantar reflexes) become evident. Cognitive impairment and behavioral disturbances emerge between ages two and three years. Persistent self-injurious behavior (biting the fingers, hands, lips, and cheeks; banging the head or limbs) is a hallmark of the disease. Overproduction of uric acid may lead to deposition of uric acid crystals or calculi in the kidneys, ureters, or bladder. Gouty arthritis may occur later in the disease. Related disorders with less severe manifestations include hyperuricemia with neurologic dysfunction but no self-injurious behavior and hyperuricemia alone, sometimes with acute renal failure.
Metachromatic leukodystrophy
MedGen UID:
6071
Concept ID:
C0023522
Disease or Syndrome
Arylsulfatase A deficiency (also known as metachromatic leukodystrophy or MLD) is characterized by three clinical subtypes: late-infantile MLD (50%-60% of cases); juvenile MLD (20%-30% of cases); and adult MLD (15%-20% of cases). Age of onset within a family is usually similar. The disease course may be from three to ten or more years in the late-infantile form and up to 20 years or more in the juvenile and adult forms. Late-infantile MLD. Onset is between ages one and two years. Typical presenting findings include weakness, hypotonia, clumsiness, frequent falls, toe walking, and slurred speech. Later signs include inability to stand, difficulty with speech, deterioration of mental function, increased muscle tone, pain in the arms and legs, generalized or partial seizures, compromised vision and hearing, and peripheral neuropathy. In the final stages children have tonic spasms, decerebrate posturing, and general unawareness of their surroundings. Juvenile MLD. Onset is between age four years and sexual maturity (age 12-14 years). Initial manifestations include decline in school performance and emergence of behavioral problems, followed by clumsiness, gait problems, slurred speech, incontinence, and bizarre behaviors. Seizures may occur. Progression is similar to but slower than the late-infantile form. Adult MLD. Onset occurs after sexual maturity, sometimes not until the fourth or fifth decade. Initial signs can include problems in school or job performance, personality changes, alcohol or drug abuse, poor money management, and emotional lability; in others, neurologic symptoms (weakness and loss of coordination progressing to spasticity and incontinence) or seizures predominate initially. Peripheral neuropathy is common. Disease course is variable, with periods of stability interspersed with periods of decline, and may extend over two to three decades. The final stage is similar to that for the earlier-onset forms.
Azorean disease
MedGen UID:
9841
Concept ID:
C0024408
Disease or Syndrome
Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is characterized by progressive cerebellar ataxia and variable findings including a dystonic-rigid syndrome, a parkinsonian syndrome, or a combined syndrome of dystonia and peripheral neuropathy. Neurologic findings tend to evolve as the disease progresses.
Parkinson's disease
MedGen UID:
10590
Concept ID:
C0030567
Disease or Syndrome
Parkinsonism refers to all clinical states characterized by tremor, muscle rigidity, slowed movement (bradykinesia) and often postural instability. Parkinson disease is the primary and most common form of parkinsonism. Psychiatric manifestations, which include depression and visual hallucinations, are common but not uniformly present. Dementia eventually occurs in at least 20% of cases. The most common sporadic form of Parkinson disease manifests around age 60; however, young-onset and even juvenile presentations are seen.
Pyruvate dehydrogenase complex deficiency
MedGen UID:
19610
Concept ID:
C0034345
Disease or Syndrome
Genetic defects in the pyruvate dehydrogenase complex are one of the most common causes of primary lactic acidosis in children. Most cases are caused by mutation in the E1-alpha subunit gene on the X chromosome. X-linked PDH deficiency is one of the few X-linked diseases in which a high proportion of heterozygous females manifest severe symptoms. The clinical spectrum of PDH deficiency is broad, ranging from fatal lactic acidosis in the newborn to chronic neurologic dysfunction with structural abnormalities in the central nervous system without systemic acidosis (Robinson et al., 1987; Brown et al., 1994). Genetic Heterogeneity of Pyruvate Dehydrogenase Complex Deficiency PDH deficiency can also be caused by mutation in other subunits of the PDH complex, including a form (PDHXD; 245349) caused by mutation in the component X gene (PDHX; 608769) on chromosome 11p; a form (PDHBD; 614111) caused by mutation in the PDHB gene (179060) on chromosome 3p; a form (PDHDD; 245348) caused by mutation in the DLAT gene (608770) on chromosome 11q; a form (PDHPD; 608782) caused by mutation in the PDP1 gene (605993) on chromosome 8q22; and a form (PDHLD; 614462) caused by mutation in the LIAS gene (607031) on chromosome 4p14.
Rett's disorder
MedGen UID:
48441
Concept ID:
C0035372
Disease or Syndrome
MECP2-related disorders in females include classic Rett syndrome, variant Rett syndrome, and mild learning disabilities. A MECP2 mutation in a male is presumed to most often be lethal; phenotypes in rare surviving males are primarily severe neonatal encephalopathy and manic-depressive psychosis, pyramidal signs, Parkinsonian, and macro-orchidism (PPM-X syndrome). Classic Rett syndrome, a progressive neurodevelopmental disorder primarily affecting girls, is characterized by apparently normal psychomotor development during the first six to 18 months of life, followed by a short period of developmental stagnation, then rapid regression in language and motor skills, followed by long-term stability. During the phase of rapid regression, repetitive, stereotypic hand movements replace purposeful hand use. Additional findings include fits of screaming and inconsolable crying, autistic features, panic-like attacks, bruxism, episodic apnea and/or hyperpnea, gait ataxia and apraxia, tremors, seizures, and acquired microcephaly. Atypical Rett syndrome is observed increasingly as MECP2 mutations are identified in individuals previously diagnosed with: clinically suspected but molecularly unconfirmed Angelman syndrome; intellectual disability with spasticity or tremor; mild learning disability; or (rarely) autism. Severe neonatal encephalopathy resulting in death before age two years is the most common phenotype observed in affected males.
Pelizaeus-Merzbacher disease
MedGen UID:
61440
Concept ID:
C0205711
Disease or Syndrome
PLP1-related disorders of central nervous system myelin formation include a range of phenotypes from Pelizaeus-Merzbacher disease (PMD) to spastic paraplegia 2 (SPG2). PMD typically manifests in infancy or early childhood with nystagmus, hypotonia, and cognitive impairment; the findings progress to severe spasticity and ataxia. Life span is shortened. SPG2 manifests as spastic paraparesis with or without CNS involvement and usually normal life span. Intrafamilial variation of phenotypes can be observed, but the signs are usually fairly consistent within families. Female carriers may manifest mild to moderate signs of the disease.
Ganglioside sialidase deficiency
MedGen UID:
68663
Concept ID:
C0238286
Disease or Syndrome
Mucolipidosis IV is characterized by severe psychomotor delay evident by the end of the first year of life and slowly progressive visual impairment during the first decade as a result of a combination of corneal clouding and retinal degeneration. By the end of the first decade of life and certainly by their early teens, all individuals with typical mucolipidosis IV have severe visual impairment as a result of retinal degeneration. Neurodegeneration is thought to occur in no more than 15% of individuals. About 5% of individuals have atypical mucolipidosis IV, often manifest as less severe psychomotor retardation and/or eye findings. About 70% of individuals with mucolipidosis IV are of Ashkenazi Jewish heritage.
Deficiency of cytochrome-b5 reductase
MedGen UID:
75661
Concept ID:
C0268193
Disease or Syndrome
Methemoglobinemia due to NADH-cytochrome b5 reductase deficiency is an autosomal recessive disorder characterized clinically by decreased oxygen carrying capacity of the blood, with resultant cyanosis and hypoxia (review by Percy and Lappin, 2008). There are 2 types of methemoglobin reductase deficiency. In type I, the defect affects the soluble form of the enzyme, is restricted to red blood cells, and causes well-tolerated methemoglobinemia. In type II, the defect affects both the soluble and microsomal forms of the enzyme and is thus generalized, affecting red cells, leukocytes, and all body tissues. Type II methemoglobinemia is associated with mental deficiency and other neurologic symptoms. The neurologic symptoms may be related to the major role played by the cytochrome b5 system in the desaturation of fatty acids (Vives-Corrons et al., 1978; Kaplan et al., 1979).
Gangliosidosis GM1 type 3
MedGen UID:
78655
Concept ID:
C0268273
Disease or Syndrome
GM1-gangliosidosis type III is an autosomal recessive lysosomal storage disorder characterized by neurodegeneration and mild skeletal changes. Age at onset ranges from 3 to 30 years. The disorder is less severe than GM1-gangliosidosis types I and II (230600). Type III shows extreme clinical variability, with some patients having only focal neurologic signs, such as dystonia, and others having more severe involvement with extrapyramidal signs and mental retardation. GLB1 enzymatic activity usually ranges from approximately 4 to 10% of control values (Suzuki et al., 2001).
Dihydropteridine reductase deficiency
MedGen UID:
75682
Concept ID:
C0268465
Disease or Syndrome
Tetrahydrobiopterin deficiency is a rare disorder characterized by a shortage (deficiency) of a molecule called tetrahydrobiopterin or BH4. This condition alters the levels of several substances in the body, including phenylalanine. Phenylalanine is a building block of proteins (an amino acid) that is obtained through the diet. It is found in foods that contain protein and in some artificial sweeteners. High levels of phenylalanine are present from early infancy in people with untreated tetrahydrobiopterin deficiency. This condition also alters the levels of chemicals called neurotransmitters, which transmit signals between nerve cells in the brain. Infants with tetrahydrobiopterin deficiency appear normal at birth, but medical problems ranging from mild to severe become apparent over time. Signs and symptoms of this condition can include intellectual disability, progressive problems with development, movement disorders, difficulty swallowing, seizures, behavioral problems, and an inability to control body temperature.
GTP cyclohydrolase I deficiency
MedGen UID:
75683
Concept ID:
C0268467
Disease or Syndrome
Tetrahydrobiopterin deficiency is a rare disorder characterized by a shortage (deficiency) of a molecule called tetrahydrobiopterin or BH4. This condition alters the levels of several substances in the body, including phenylalanine. Phenylalanine is a building block of proteins (an amino acid) that is obtained through the diet. It is found in foods that contain protein and in some artificial sweeteners. High levels of phenylalanine are present from early infancy in people with untreated tetrahydrobiopterin deficiency. This condition also alters the levels of chemicals called neurotransmitters, which transmit signals between nerve cells in the brain. Infants with tetrahydrobiopterin deficiency appear normal at birth, but medical problems ranging from mild to severe become apparent over time. Signs and symptoms of this condition can include intellectual disability, progressive problems with development, movement disorders, difficulty swallowing, seizures, behavioral problems, and an inability to control body temperature.
Sepiapterin reductase deficiency
MedGen UID:
120642
Concept ID:
C0268468
Disease or Syndrome
SPR deficiency results in neurologic deterioration due to severe dopamine and serotonin deficiencies in the central nervous system caused by a defect in BH4 synthesis. Clinically, affected individuals show an L-DOPA-responsive, diurnally fluctuating movement disorder usually associated with cognitive delay and severe neurologic dysfunction. BH4 is a required cofactor for the synthesis of the neurotransmitters dopamine and serotonin. BH4 is also a required cofactor for phenylalanine hydroxylase (PAH; 612349), but patients with SPR deficiency do not exhibit overt hyperphenylalaninemia. The lack of hyperphenylalaninemia distinguishes SPR deficiency from other disorders of BH4 synthesis (see, e.g., HPABH4A, 261640). However, the neurologic phenotype of SPR deficiency resembles the other BH4-deficient disorders (summary by Bonafe et al., 2001 and Friedman et al., 2012). Another form of dopa-responsive dystonia (DTY5; 128230) is caused by mutation in the gene encoding GTP cyclohydrolase I (GCH1; 600225), which is also a component of the biopterin synthetic pathway.
Propionic acidemia
MedGen UID:
75694
Concept ID:
C0268579
Disease or Syndrome
The spectrum of propionic acidemia (PA) ranges from neonatal-onset to late-onset disease. Neonatal-onset PA, the most common form, is characterized by poor feeding, vomiting, and somnolence in the first days of life in a previously healthy infant, followed by lethargy, seizures, coma, and death. It is frequently accompanied by metabolic acidosis with anion gap, ketonuria, hypoglycemia, hyperammonemia, and cytopenias. Late-onset PA includes developmental regression, chronic vomiting, protein intolerance, failure to thrive, hypotonia, and occasionally basal ganglia infarction (resulting in dystonia and choreoathetosis) and cardiomyopathy. Affected children can have an acute decompensation that resembles the neonatal presentation and is precipitated by a catabolic stress such as infection, injury, or surgery. Isolated cardiomyopathy and arrhythmia can be observed on rare occasion in the absence of clinical metabolic decompensation or neurocognitive deficits. Manifestations of neonatal and late-onset PA over time can include growth impairment, intellectual disability, seizures, basal ganglia lesions, pancreatitis, and cardiomyopathy. Other rarely reported complications include optic atrophy, hearing loss, premature ovarian insufficiency (POI), and chronic renal failure.
Glutaric aciduria, type 1
MedGen UID:
124337
Concept ID:
C0268595
Disease or Syndrome
The term "organic acidemia" or "organic aciduria" (OA) applies to a group of disorders characterized by the excretion of non-amino organic acids in urine. Most organic acidemias result from dysfunction of a specific step in amino acid catabolism, usually the result of deficient enzyme activity. The majority of the classic organic acid disorders are caused by abnormal amino acid catabolism of branched-chain amino acids or lysine. They include maple syrup urine disease (MSUD), propionic acidemia, methylmalonic acidemia (MMA), methylmalonic aciduria and homocystinuria, isovaleric acidemia, biotin-unresponsive 3-methylcrotonyl-CoA carboxylase deficiency, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase deficiency, ketothiolase deficiency, and glutaricacidemia type I (GA I). A neonate affected with an OA is usually well at birth and for the first few days of life. The usual clinical presentation is that of toxic encephalopathy and includes vomiting, poor feeding, neurologic symptoms such as seizures and abnormal tone, and lethargy progressing to coma. Outcome is enhanced by diagnosis and treatment in the first ten days of life. In the older child or adolescent, variant forms of the OAs can present as loss of intellectual function, ataxia or other focal neurologic signs, Reye syndrome, recurrent ketoacidosis, or psychiatric symptoms.
Hepatic methionine adenosyltransferase deficiency
MedGen UID:
75700
Concept ID:
C0268621
Disease or Syndrome
Methionine adenosyltransferase deficiency is an inborn error of metabolism resulting in isolated hypermethioninemia. Most patients have no clinical abnormalities, although some neurologic abnormalities have been reported in rare cases with severe loss of enzyme activity (Mudd et al., 2003).
Alternating hemiplegia of childhood
MedGen UID:
90925
Concept ID:
C0338488
Disease or Syndrome
Alternating hemiplegia of childhood is a rare syndrome of episodic hemi- or quadriplegia lasting minutes to days. Most cases are accompanied by dystonic posturing, choreoathetoid movements, nystagmus, other ocular motor abnormalities, autonomic disturbances, and progressive cognitive impairment (Mikati et al., 1992). The disorder may mimic or overlap with other disorders, including familial hemiplegic migraine (FHM1; 141500) and GLUT1 deficiency syndrome (606777) (Rotstein et al., 2009). Genetic Heterogeneity of Alternating Hemiplegia of Childhood See also AHC2 (614820), caused by mutation in the ATP1A3 gene (182350).
Hypogonadism, diabetes mellitus, alopecia, mental retardation and electrocardiographic abnormalities
MedGen UID:
83337
Concept ID:
C0342286
Congenital Abnormality
Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurologic disorders in which iron accumulates in the basal ganglia resulting in progressive dystonia, spasticity, parkinsonism, neuropsychiatric abnormalities, and optic atrophy or retinal degeneration. Ten types and their associated genes are recognized. The age of onset ranges from infancy to late adulthood; the rate of progression varies. Cognitive decline occurs in some subtypes, but more often cognition is relatively spared. Cerebellar atrophy is a frequent finding in some subtypes.
3-Methylglutaconic aciduria
MedGen UID:
90994
Concept ID:
C0342727
Disease or Syndrome
Type I MGCA is a rare autosomal recessive disorder of leucine catabolism. The metabolic landmark is urinary excretion of 3-methylglutaconic acid (3-MGA) and its derivatives 3-methylglutaric acid (3-MG) and 3-hydroxyisovaleric acid (3-HIVA). Two main presentations have been described: 1 with onset in childhood associated with the nonspecific finding of psychomotor retardation, and the other with onset in adulthood of a progressive neurodegenerative disorder characterized by ataxia, spasticity, and sometimes dementia; these patients develop white matter lesions in the brain. However, some asymptomatic pediatric patients have been identified by newborn screening and show no developmental abnormalities when reexamined later in childhood (summary by Wortmann et al., 2010). Genetic Heterogeneity and Classification of Methylglutaconic Aciduria Methylglutaconic aciduria is a clinically and genetically heterogeneous disorder. Type II MGCA, also known as Barth syndrome (BTHS; 302060), is caused by mutation in the tafazzin gene (TAZ; 300394) on chromosome Xq28. It is characterized by mitochondrial cardiomyopathy, short stature, skeletal myopathy, and recurrent infections; cognitive development is normal. Type III MGCA (258501), caused by mutation in the OPA3 gene (606580) on chromosome 19q13.2-q13.3, occurs in Iraqi Jews and involves optic atrophy, movement disorder, and spastic paraplegia. In types II and III, the elevations of 3-methylglutaconate and 3-methylglutarate in urine are modest. Type IV MGCA (250951) represents an unclassified group of patients who have severe psychomotor retardation and cerebellar dysgenesis. Type V MGCA (610198), caused by mutation in the DNAJC19 gene (608977) on chromosome 3q26.33, is characterized by early-onset dilated cardiomyopathy with conduction defects, nonprogressive cerebellar ataxia, testicular dysgenesis, and growth failure in addition to 3-methylglutaconic aciduria (Chitayat et al., 1992; Davey et al., 2006). Eriguchi et al. (2006) noted that type I MGCA is very rare, with only 13 patients reported in the literature as of 2003.
Choreoacanthocytosis
MedGen UID:
98277
Concept ID:
C0393576
Disease or Syndrome
Chorea-acanthocytosis (ChAc) is characterized by a progressive movement disorder, cognitive and behavior changes, a myopathy that can be subclinical, and chronic hyperCKemia in serum. Although the disorder is named for acanthocytosis of the red blood cells, this feature is variable. The movement disorder is mostly limb chorea, but some individuals present with parkinsonism. Dystonia is common and affects the oral region and especially the tongue, causing dysarthria and serious dysphagia with resultant weight loss. Habitual tongue and lip biting are characteristic, as well as tongue protrusion dystonia. Progressive cognitive and behavioral changes resemble those in a frontal lobe syndrome. Seizures are observed in almost half of affected individuals and can be the initial manifestation. Myopathy results in progressive distal muscle wasting and weakness. Mean age of onset in ChAc is about 30 years, although ChAc can develop as early as the first decade or as late as the seventh decade. It runs a chronic progressive course and may lead to major disability within a few years. Life expectancy is reduced, with age of death ranging from 28 to 61 years.
Idiopathic basal ganglia calcification 1
MedGen UID:
97952
Concept ID:
C0393590
Disease or Syndrome
Primary familial brain calcification (PFBC) is a neurodegenerative disorder with characteristic calcium deposits in the basal ganglia and other brain areas visualized on neuroimaging. Most affected individuals are in good health during childhood and young adulthood and typically present in the fourth to fifth decade with gradually progressive neuropsychiatric and movement disorders. The main manifestations include clumsiness, fatigability, unsteady gait, slow or slurred speech, dysphagia, involuntary movements, or muscle cramping. Migraine is frequent and seizures of various types may also occur. Neuropsychiatric symptoms, often the first or most prominent manifestations, range from mild difficulty with concentration and memory to changes in personality and/or behavior, to psychosis and dementia.
Deletion of short arm of chromosome 18
MedGen UID:
96604
Concept ID:
C0432442
Disease or Syndrome
Deletion of the short arm of chromosome 18. It is one of the most fre quently occurring chromosomal aberrations with minimal abnormalities visible at birth, which become more apparent at the age of three years. The phenotype is marked mainly by holoprosencephaly, brachycephaly, broad facies, blepharoptosis, downturned corners of the mouth, tooth abnormalities, broad neck with low posterior hairline, funnel chest, enlarged labia majora, hand abnormalities, mental retardation ranging from mild to severe, and other malformations. The phenotype varies from case to case, frequently reflecting the length and type of deletion: del(18p) mosaicism is associated with abnormalities which are similar to those in del(18p) and include microphthalmia and cataract and cyclopia may occur in del(18p) in mosaicism with dup(18p).
Filippi syndrome
MedGen UID:
163197
Concept ID:
C0795940
Disease or Syndrome
Filippi syndrome is characterized by short stature, microcephaly, syndactyly, intellectual disability, and facial dysmorphism consisting of bulging forehead, broad and prominent nasal bridge, and diminished alar flare. Common features include cryptorchidism, speech impairment, and clinodactyly of the fifth finger, Some patients exhibit visual disturbances, polydactyly, seizures, and/or ectodermal abnormalities, such as nail hypoplasia, long eyelashes, hirsutism, and microdontia (summary by Hussain et al., 2014).
Striatonigral degeneration infantile
MedGen UID:
167090
Concept ID:
C0795996
Disease or Syndrome
Bilateral striatal necrosis (BSN) encompasses a heterogeneous group of neurologic disorders with different causation. Familial infantile striatal degeneration is rare and can be inherited as an autosomal recessive or mitochondrial (see 500003) disorder. The familial form has an insidious onset and a slowly progressive course; the sporadic form is associated with acute systemic illness. Many features of BSN overlap with Leigh syndrome (256000) and certain metabolic disorders, including glutaric acidemia I (231670) and methylmalonic aciduria (251000). See also Aicardi-Goutieres syndrome (225750) (Mito et al., 1986; De Meirleir et al., 1995). See also adult-onset autosomal dominant striatal degeneration (ADSD; 609161), a less severe disorder caused by mutation in the PDE8B gene (603390) on chromosome 5q13.
Mohr-Tranebjaerg syndrome
MedGen UID:
162903
Concept ID:
C0796074
Disease or Syndrome
Males with deafness-dystonia-optic neuronopathy (DDON) syndrome have prelingual or postlingual sensorineural hearing impairment in early childhood, slowly progressive dystonia or ataxia in the teens, slowly progressive decreased visual acuity from optic atrophy beginning approximately age 20 years, and dementia beginning at approximately age 40 years. Psychiatric symptoms such as personality change and paranoia may appear in childhood and progress. The hearing impairment appears to be consistent in age of onset and progression, whereas the neurologic, visual, and neuropsychiatric signs vary in degree of severity and rate of progression. Females may have mild hearing impairment and focal dystonia.
Aicardi Goutieres syndrome 1
MedGen UID:
162912
Concept ID:
C0796126
Disease or Syndrome
Most characteristically, Aicardi-Goutières syndrome (AGS) manifests as an early-onset encephalopathy that usually, but not always, results in severe intellectual and physical handicap. A subgroup of infants with AGS present at birth with abnormal neurologic findings, hepatosplenomegaly, elevated liver enzymes, and thrombocytopenia, a picture highly suggestive of congenital infection. Otherwise, most affected infants present at variable times after the first few weeks of life, frequently after a period of apparently normal development. Typically, they demonstrate the subacute onset of a severe encephalopathy characterized by extreme irritability, intermittent sterile pyrexias, loss of skills, and slowing of head growth. Over time, as many as 40% develop chilblain skin lesions on the fingers, toes, and ears. It is becoming apparent that atypical, sometimes milder, cases of AGS exist, and thus the true extent of the phenotype associated with mutation of the AGS-related genes is not yet known. For example, mutation of ADAR has recently been associated with a clinical presentation of acute bilateral striatal necrosis.
Wieacker syndrome
MedGen UID:
163227
Concept ID:
C0796200
Disease or Syndrome
Wieacker-Wolff syndrome is a severe X-linked recessive neurodevelopmental disorder affecting the central and peripheral nervous systems. It is characterized by onset of muscle weakness in utero (fetal akinesia). Affected boys are born with severe contractures, known as arthrogryposis, and have delayed motor development, facial and bulbar weakness, characteristic dysmorphic facial features, and skeletal abnormalities, such as hip dislocation, scoliosis, and pes equinovarus. Those that survive infancy show mental retardation. Carrier females may have mild features of the disorder (summary by Hirata et al., 2013).
6-pyruvoyl-tetrahydropterin synthase deficiency
MedGen UID:
209234
Concept ID:
C0878676
Disease or Syndrome
Tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia (HPA) comprises a genetically heterogeneous group of progressive neurologic disorders caused by autosomal recessive mutations in the genes encoding enzymes involved in the synthesis or regeneration of BH4. BH4 is a cofactor for phenylalanine hydroxylase (PAH; 612349), tyrosine hydroxylase (TH; 191290) and tryptophan hydroxylase (TPH1; 191060), the latter 2 of which are involved in neurotransmitter synthesis. The BH4-deficient HPAs are characterized phenotypically by hyperphenylalaninemia, depletion of the neurotransmitters dopamine and serotonin, and progressive cognitive and motor deficits (Dudesek et al., 2001). HPABH4A, caused by mutations in the PTS gene, represents the most common cause of BH4-deficient hyperphenylalaninemia (Dudesek et al., 2001). Other forms of BH4-deficient HPA include HPABH4B (233910), caused by mutation in the GCH1 gene (600225), HPABH4C (261630), caused by mutation in the QDPR gene (612676), and HPABH4D (264070), caused by mutation in the PCBD1 gene (126090). Niederwieser et al. (1982) noted that about 1 to 3% of patients with hyperphenylalaninemia have one of these BH4-deficient forms. These disorders are clinically and genetically distinct from classic phenylketonuria (PKU; 261600), caused by mutation in the PAH gene. Two additional disorders associated with BH4 deficiency and neurologic symptoms do not have overt hyperphenylalaninemia as a feature: dopa-responsive dystonia (612716), caused by mutation in the SPR gene (182125), and autosomal dominant dopa-responsive dystonia (DYT5; 128230), caused by mutation in the GCH1 gene. Patients with these disorders may develop hyperphenylalaninemia when stressed.
Leber's optic atrophy
MedGen UID:
182973
Concept ID:
C0917796
Disease or Syndrome
Mitochondrial diseases are a clinically heterogeneous group of disorders that arise as a result of dysfunction of the mitochondrial respiratory chain. They can be caused by mutation of genes encoded by either nuclear DNA or mitochondrial DNA (mtDNA). While some mitochondrial disorders only affect a single organ (e.g., the eye in Leber hereditary optic neuropathy [LHON]), many involve multiple organ systems and often present with prominent neurologic and myopathic features. Mitochondrial disorders may present at any age. Many individuals with a mutation of mtDNA display a cluster of clinical features that fall into a discrete clinical syndrome, such as the Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO), mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), myoclonic epilepsy with ragged-red fibers (MERRF), neurogenic weakness with ataxia and retinitis pigmentosa (NARP), or Leigh syndrome (LS). However, considerable clinical variability exists and many individuals do not fit neatly into one particular category, which is well-illustrated by the overlapping spectrum of disease phenotypes (including mitochondrial recessive ataxia syndrome (MIRAS) resulting from mutation of the nuclear gene POLG, which has emerged as a major cause of mitochondrial disease. Common clinical features of mitochondrial disease – whether involving a mitochondrial or nuclear gene – include ptosis, external ophthalmoplegia, proximal myopathy and exercise intolerance, cardiomyopathy, sensorineural deafness, optic atrophy, pigmentary retinopathy, and diabetes mellitus. Common central nervous system findings are fluctuating encephalopathy, seizures, dementia, migraine, stroke-like episodes, ataxia, and spasticity. A high incidence of mid- and late pregnancy loss is a common occurrence that often goes unrecognized.
Deficiency of beta-ureidopropionase
MedGen UID:
226944
Concept ID:
C1291512
Disease or Syndrome
Beta-ureidopropionase deficiency is a very rare autosomal recessive inborn error of metabolism due to a defect in pyrimidine degradation. Less than 10 patients have been reported, and the phenotype can range from severe neurologic involvement with mental retardation and seizures to normal neurologic development (Yaplito-Lee et al., 2008).
Episodic ataxia type 2
MedGen UID:
314039
Concept ID:
C1720416
Disease or Syndrome
Episodic ataxia type 2 (EA2) is characterized by paroxysmal attacks of ataxia, vertigo, and nausea typically lasting minutes to days in duration. Attacks can be associated with dysarthria, diplopia, tinnitus, dystonia, hemiplegia, and headache. About 50% of individuals with EA2 have migraine headaches. Onset is typically in childhood or early adolescence (age range 2-32 years). Frequency of attacks can range from once or twice a year to three or four times a week. Attacks can be triggered by stress, exertion, caffeine, alcohol, fever, heat, and phenytoin and can be stopped or decreased in frequency and severity by administration of acetazolamide. Between attacks, individuals may initially be asymptomatic but eventually develop interictal findings that can include nystagmus and ataxia.
Choreoathetosis/spasticity, episodic
MedGen UID:
371427
Concept ID:
C1832855
Disease or Syndrome
Dystonia-9 is an autosomal dominant neurologic disorder characterized by childhood onset of paroxysmal choreoathetosis and progressive spastic paraplegia. Most show some degree of cognitive impairment. Other variable features may include seizures, migraine headaches, and ataxia (summary by Weber et al., 2011).
Frontotemporal Dementia, Chromosome 3-Linked
MedGen UID:
318833
Concept ID:
C1833296
Disease or Syndrome
Chromosome 3-linked frontotemporal dementia (FTD3) has been described in a single family from Denmark and in one individual with familial FTD3 from Belgium. It typically starts between ages 46 and 65 years with subtle personality changes and slowly progressive behavioral changes, dyscalculia, and language disturbances. Disinhibition or loss of initiative is the most common presenting symptom. The disease progresses over a few years into profound dementia with mutism. Several individuals have developed an asymmetric akinetic rigid syndrome with arm and gait dystonia and pyramidal signs that may be related to treatment with neuroleptic drugs. Disease duration may be as short as three years or longer than 20 years.
Inclusion body myopathy with early-onset paget disease and frontotemporal dementia
MedGen UID:
322251
Concept ID:
C1833662
Disease or Syndrome
Inclusion body myopathy associated with Paget disease of bone (PDB) and/or frontotemporal dementia (IBMPFD) is characterized by adult-onset proximal and distal muscle weakness (clinically resembling a limb-girdle muscular dystrophy syndrome), early-onset PDB, and premature frontotemporal dementia (FTD). Muscle weakness progresses to involve other limb and respiratory muscles. Cardiac failure and cardiomyopathy have been observed in later stages. PDB involves focal areas of increased bone turnover that typically lead to spine and/or hip pain and localized enlargement and deformity of the long bones; pathologic fractures occur on occasion. Early stages of FTD are characterized by dysnomia, dyscalculia, comprehension deficits, paraphasic errors, and relative preservation of memory, and later stages by inability to speak, auditory comprehension deficits for even one-step commands, alexia, and agraphia. Mean age at diagnosis for muscle disease and PDB is 42 years; for FTD, 55 years.
Aicardi Goutieres syndrome 4
MedGen UID:
332084
Concept ID:
C1835912
Disease or Syndrome
Most characteristically, Aicardi-Goutières syndrome (AGS) manifests as an early-onset encephalopathy that usually, but not always, results in severe intellectual and physical handicap. A subgroup of infants with AGS present at birth with abnormal neurologic findings, hepatosplenomegaly, elevated liver enzymes, and thrombocytopenia, a picture highly suggestive of congenital infection. Otherwise, most affected infants present at variable times after the first few weeks of life, frequently after a period of apparently normal development. Typically, they demonstrate the subacute onset of a severe encephalopathy characterized by extreme irritability, intermittent sterile pyrexias, loss of skills, and slowing of head growth. Over time, as many as 40% develop chilblain skin lesions on the fingers, toes, and ears. It is becoming apparent that atypical, sometimes milder, cases of AGS exist, and thus the true extent of the phenotype associated with mutation of the AGS-related genes is not yet known. For example, mutation of ADAR has recently been associated with a clinical presentation of acute bilateral striatal necrosis.
Aicardi Goutieres syndrome 3
MedGen UID:
324389
Concept ID:
C1835916
Disease or Syndrome
Most characteristically, Aicardi-Goutières syndrome (AGS) manifests as an early-onset encephalopathy that usually, but not always, results in severe intellectual and physical handicap. A subgroup of infants with AGS present at birth with abnormal neurologic findings, hepatosplenomegaly, elevated liver enzymes, and thrombocytopenia, a picture highly suggestive of congenital infection. Otherwise, most affected infants present at variable times after the first few weeks of life, frequently after a period of apparently normal development. Typically, they demonstrate the subacute onset of a severe encephalopathy characterized by extreme irritability, intermittent sterile pyrexias, loss of skills, and slowing of head growth. Over time, as many as 40% develop chilblain skin lesions on the fingers, toes, and ears. It is becoming apparent that atypical, sometimes milder, cases of AGS exist, and thus the true extent of the phenotype associated with mutation of the AGS-related genes is not yet known. For example, mutation of ADAR has recently been associated with a clinical presentation of acute bilateral striatal necrosis.
Spastic paraplegia 26
MedGen UID:
373138
Concept ID:
C1836632
Disease or Syndrome
SPG26 is an autosomal recessive form of complicated spastic paraplegia characterized by onset in the first 2 decades of life of gait abnormalities due to lower limb spasticity and muscle weakness. Some patients have upper limb involvement. Additional features include intellectual disability, peripheral neuropathy, dysarthria, cerebellar signs, extrapyramidal signs, and cortical atrophy. The disorder is slowly progressive (summary by Boukhris et al., 2013). For a discussion of genetic heterogeneity of autosomal recessive SPG, see SPG5A (270800).
Leukodystrophy, hypomyelinating, 2
MedGen UID:
325157
Concept ID:
C1837355
Disease or Syndrome
Leber hereditary optic neuropathy with dystonia
MedGen UID:
333240
Concept ID:
C1839040
Disease or Syndrome
Pyruvate dehydrogenase E1-alpha deficiency
MedGen UID:
326487
Concept ID:
C1839414
Disease or Syndrome
Dystonia 18
MedGen UID:
330866
Concept ID:
C1842534
Disease or Syndrome
The phenotypic spectrum of glucose transporter type 1 deficiency syndrome (Glut1-DS) is now known to be a continuum that includes the classic phenotype as well as dystonia 9, dystonia 18, atypical childhood absence epilepsy, myoclonic astatic epilepsy, and paroxysmal non-epileptic findings such as intermittent ataxia, choreoathetosis, dystonia, and alternating hemiplegia. The classic phenotype is characterized by infantile-onset seizures, delayed neurologic development, acquired microcephaly, and complex movement disorders. Seizures begin before age two years in approximately 90% and later in approximately 10%. Several seizure types occur: generalized tonic or clonic, focal, myoclonic, atypical absence, atonic, and unclassified. The frequency, severity, and type of seizures vary among affected individuals and are not related to disease severity. Cognitive impairment, ranging from learning disabilities to severe intellectual disability, is typical. The complex movement disorder, characterized by ataxia, dystonia, and chorea, may occur in any combination and may be continuous, paroxysmal, or continuous with fluctuations in severity influenced by environmental factors such as fasting, fever, and intercurrent infection. Symptoms often improve substantially when a ketogenic diet is started.
Alzheimer disease, type 3
MedGen UID:
334304
Concept ID:
C1843013
Disease or Syndrome
Alzheimer disease (AD) is characterized by adult-onset progressive dementia associated with cerebral cortical atrophy, beta-amyloid plaque formation, and intraneuronal neurofibrillary tangles. AD typically begins with subtle memory failure that becomes more severe and is eventually incapacitating. Other common findings include confusion, poor judgment, language disturbance, agitation, withdrawal, hallucinations, seizures, Parkinsonian features, increased muscle tone, myoclonus, incontinence, and mutism. Familial AD (FAD) characterizes families that have more than one member with AD and usually implies multiple affected persons in more than one generation. Early-onset FAD (EOFAD) refers to families in which onset is consistently before age 60 to 65 years and often before age 55 years.
Niemann-Pick disease type C2
MedGen UID:
335942
Concept ID:
C1843366
Disease or Syndrome
Niemann-Pick disease type C (NPC) is a lipid storage disease that can present in infants, children, or adults. Neonates can present with ascites and severe liver disease from infiltration of the liver and/or respiratory failure from infiltration of the lungs. Other infants, without liver or pulmonary disease, have hypotonia and developmental delay. The classic presentation occurs in mid-to-late childhood with the insidious onset of ataxia, vertical supranuclear gaze palsy (VSGP), and dementia. Dystonia and seizures are common. Dysarthria and dysphagia eventually become disabling, making oral feeding impossible; death usually occurs in the late second or third decade from aspiration pneumonia. Adults are more likely to present with dementia or psychiatric symptoms.
Spastic paraplegia, ataxia, and mental retardation
MedGen UID:
336010
Concept ID:
C1843661
Disease or Syndrome
Dystonia 15, myoclonic
MedGen UID:
334492
Concept ID:
C1843786
Disease or Syndrome
Basal ganglia disease, biotin-responsive
MedGen UID:
375289
Concept ID:
C1843807
Congenital Abnormality
Biotin-thiamine-responsive basal ganglia disease (BTBGD) is characterized by recurrent subacute encephalopathy manifest as confusion, seizures, ataxia, dystonia, supranuclear facial palsy, external ophthalmoplegia, and/or dysphagia which - if left untreated - can eventually lead to coma and even death. Dystonia and cogwheel rigidity are nearly always present; hyperreflexia, ankle clonus, and Babinski responses are common. Hemiparesis or quadriparesis may be seen. Episodes are often triggered by febrile illness or mild trauma or surgery. Less frequently, BTBGD presents as chronic or slowly progressive dystonia, seizures, and/or psychomotor delay. Although onset is usually in childhood (ages three to ten 10 years), it is extremely variable, ranging from the newborn period to adulthood. Prompt administration of biotin and thiamine early in the disease course results in partial or complete improvement within days.
Chromosome Xq28 deletion syndrome
MedGen UID:
336933
Concept ID:
C1845408
Disease or Syndrome
Deafness, dystonia, and cerebral hypomyelination is an X-linked recessive mental retardation syndrome characterized by almost no psychomotor development, dysmorphic facial features, sensorineural deafness, dystonia, pyramidal signs, and hypomyelination on brain imaging (summary by Cacciagli et al., 2013).
Creatine deficiency, X-linked
MedGen UID:
337451
Concept ID:
C1845862
Disease or Syndrome
The cerebral creatine deficiency syndromes (CCDS), inborn errors of creatine metabolism, include the two creatine biosynthesis disorders, guanidinoacetate methyltransferase (GAMT) deficiency and L-arginine:glycine amidinotransferase (AGAT or GATM) deficiency, and the creatine transporter (SLC6A8) deficiency. Intellectual disability and seizures are common to all three CCDS. The majority of individuals with GAMT deficiency have a behavior disorder that can include autistic behaviors and self-mutilation; a significant proportion have pyramidal/extrapyramidal findings. Onset is between ages three months and three years. Only seven individuals with AGAT deficiency have been reported. The phenotype of SLC6A8 deficiency in affected males ranges from mild intellectual disability and speech delay to severe intellectual disability, seizures, and behavior disorder; age at diagnosis ranges from two to 66 years. Females heterozygous for SLC6A8 deficiency may have learning and behavior problems.
Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration
MedGen UID:
337612
Concept ID:
C1846582
Disease or Syndrome
Pantothenate kinase-associated neurodegeneration (PKAN) is a form of neurodegeneration with brain iron accumulation, or NBIA (formerly called Hallervorden-Spatz syndrome). PKAN is characterized by progressive dystonia and basal ganglia iron deposition with onset that usually occurs before age ten years. Commonly associated features include dysarthria, rigidity, and pigmentary retinopathy. Approximately 25% of affected individuals have an 'atypical' presentation with later onset (age >10 years), prominent speech defects, psychiatric disturbances, and more gradual progression of disease.
Spinocerebellar ataxia 17
MedGen UID:
337637
Concept ID:
C1846707
Disease or Syndrome
Spinocerebellar ataxia type 17 (SCA17) is characterized by ataxia, dementia, and involuntary movements, including chorea and dystonia. Psychiatric symptoms, pyramidal signs, and rigidity are common. The age of onset ranges from three to 55 years. Individuals with full-penetrance alleles develop neurologic and/or psychiatric symptoms by age 50 years. Ataxia and psychiatric abnormalities are frequently the initial findings, followed by involuntary movement, parkinsonism, dementia, and pyramidal signs. Brain MRI shows variable atrophy of the cerebrum, brain stem, and cerebellum. The clinical features correlate with the length of the polyglutamine expansion but are not absolutely predictive of the clinical course
Spinocerebellar ataxia autosomal recessive 5
MedGen UID:
376048
Concept ID:
C1847114
Disease or Syndrome
Dyskinesia, familial, with facial myokymia
MedGen UID:
338280
Concept ID:
C1847627
Disease or Syndrome
Familial dyskinesia with facial myokymia is an autosomal dominant movement disorder characterized by childhood onset of involuntary choreiform or dystonic movements that involve the limb and facial muscles. The severity is variable, but can result in difficulty walking and talking (summary by Chen et al., 2014).
Huntington disease-like 2
MedGen UID:
341120
Concept ID:
C1847987
Disease or Syndrome
Huntington disease-like 2 (HDL2) typically presents in midlife with a relentless progressive triad of movement, emotional, and cognitive abnormalities progressing to death over ten to 20 years. In some individuals the presentation resembles juvenile-onset Huntington disease (HD) or the Westphal variant of HD, usually presenting in the fourth decade (ages 29 to 41 years) with diminished coordination and weight loss despite increase in food intake. Neurologic abnormalities include parkinsonism (rigidity, bradykinesia, tremor), dysarthria, and hyperreflexia. In others the presentation is more variable but, in general, corresponds to typical HD.
Methylmalonic acidemia with homocystinuria cblD
MedGen UID:
341253
Concept ID:
C1848552
Disease or Syndrome
The clinical manifestations of disorders of intracellular cobalamin metabolism can be highly variable even within a single complementation group. The prototype and best understood is cblC; it is also the most common of these disorders. The age of initial presentation of cblC spans a wide range, including: Newborns, who can have intrauterine growth retardation (IUGR) and microcephaly; Infants, who can have poor feeding, failure to thrive, pallor, and neurologic signs, and occasionally hemolytic uremic syndrome (HUS) and/or seizures including infantile spasms; Toddlers, who can have failure to thrive, poor head growth, cytopenias (including megaloblastic anemia), global developmental delay, encephalopathy, and neurologic signs such as hypotonia and seizures; and Adolescents and adults, who can have neuropsychiatric symptoms, progressive cognitive decline, and/or subacute combined degeneration of the spinal cord.
Pseudoneonatal adrenoleukodystrophy
MedGen UID:
376636
Concept ID:
C1849678
Disease or Syndrome
Peroxisomal acyl-CoA oxidase deficiency is a disorder of peroxisomal fatty acid beta-oxidation. See also D-bifunctional protein deficiency (261515), caused by mutation in the HSD17B4 gene (601860) on chromosome 5q2. The clinical manifestations of these 2 deficiencies are similar to those of disorders of peroxisomal assembly, including Zellweger cerebrohepatorenal syndrome (see 214100) and neonatal adrenoleukodystrophy (see 601539) (Watkins et al., 1995).
Parkinson disease 15
MedGen UID:
337969
Concept ID:
C1850100
Disease or Syndrome
Parkinsonism refers to all clinical states characterized by tremor, muscle rigidity, slowed movement (bradykinesia) and often postural instability. Parkinson disease is the primary and most common form of parkinsonism. Psychiatric manifestations, which include depression and visual hallucinations, are common but not uniformly present. Dementia eventually occurs in at least 20% of cases. The most common sporadic form of Parkinson disease manifests around age 60; however, young-onset and even juvenile presentations are seen.
Navajo neurohepatopathy
MedGen UID:
338045
Concept ID:
C1850406
Disease or Syndrome
MPV17-related hepatocerebral mitochondrial DNA (mtDNA) depletion syndrome is characterized by infantile-onset liver dysfunction that typically progresses to liver failure; neurologic involvement (developmental delay, hypotonia, and muscle weakness in the majority; ataxia, seizures, and motor and sensory peripheral neuropathy in some); failure to thrive; and metabolic derangements including lactic acidosis and hypoglycemic crises. Less frequent manifestations include renal tubulopathy, hypoparathyroidism, gastrointestinal dysmotility, and corneal anesthesia. Progressive liver disease often leads to death in infancy or early childhood. Hepatocellular carcinoma has been reported.
Spinocerebellar ataxia 28
MedGen UID:
339941
Concept ID:
C1853249
Disease or Syndrome
Spinocerebellar ataxia type 28 (SCA28) is characterized by young-adult onset, slowly progressive gait and limb ataxia, dysarthria, hyperreflexia of the lower limbs, nystagmus, and ophthalmoparesis. The usual age at onset is early adulthood (24.4 ± 14.9 years); range is from age three to 60 years. The course of the disease is slowly progressive without impairment of functional autonomy even decades after onset.
Spinocerebellar ataxia autosomal recessive 1
MedGen UID:
340052
Concept ID:
C1853761
Disease or Syndrome
Ataxia with oculomotor apraxia type 2 (AOA2) is characterized by onset between age three and 30 years, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia, and elevated serum concentration of alpha-fetoprotein (AFP).
Parkinson disease 6, autosomal recessive early-onset
MedGen UID:
342982
Concept ID:
C1853833
Disease or Syndrome
The PINK1 type of young-onset Parkinson disease is characterized by variable combinations of rigidity, bradykinesia, and rest tremor, often making it clinically indistinguishable from idiopathic Parkinson disease. Lower-limb dystonia may be a presenting sign. Onset usually occurs in the third or fourth decade. The disease is slowly progressive. Clinical signs vary; hyperreflexia may be present and abnormal behavior and/or psychiatric manifestations have been described. Dyskinesias as a result of treatment with levodopa frequently occur, as with all individuals with young-onset disease, regardless of the underlying genetic cause.
Mitochondrial complex II deficiency
MedGen UID:
344401
Concept ID:
C1855008
Disease or Syndrome
Complex II, also known as succinate dehydrogenase (EC 1.3.5.1), is part of the mitochondrial respiratory chain. Deficiency of complex II is characterized by highly variable phenotypic expression.
Pyruvate dehydrogenase E3-binding protein deficiency
MedGen UID:
343383
Concept ID:
C1855553
Disease or Syndrome
Pyruvate dehydrogenase deficiency is characterized by the buildup of a chemical called lactic acid in the body and a variety of neurological problems. Signs and symptoms of this condition usually first appear shortly after birth, and they can vary widely among affected individuals. The most common feature is a potentially life-threatening buildup of lactic acid (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. People with pyruvate dehydrogenase deficiency usually have neurological problems as well. Most have delayed development of mental abilities and motor skills such as sitting and walking. Other neurological problems can include intellectual disability, seizures, weak muscle tone (hypotonia), poor coordination, and difficulty walking. Some affected individuals have abnormal brain structures, such as underdevelopment of the tissue connecting the left and right halves of the brain (corpus callosum), wasting away (atrophy) of the exterior part of the brain known as the cerebral cortex, or patches of damaged tissue (lesions) on some parts of the brain. Because of the severe health effects, many individuals with pyruvate dehydrogenase deficiency do not survive past childhood, although some may live into adolescence or adulthood.
Dystonia with ringbinden
MedGen UID:
346509
Concept ID:
C1857089
Disease or Syndrome
Neurodegeneration with brain iron accumulation 2b
MedGen UID:
346658
Concept ID:
C1857747
Disease or Syndrome
PLA2G6-associated neurodegeneration (PLAN) comprises a continuum of three phenotypes with overlapping clinical and radiologic features: Classic infantile neuroaxonal dystrophy (INAD). Atypical neuroaxonal dystrophy (atypical NAD). PLA2G6-related dystonia-parkinsonism. INAD usually begins between ages six months and three years with developmental regression, hypotonia, progressive psychomotor delay, and progressive spastic tetraparesis. Strabismus, nystagmus, and optic atrophy are common. Disease progression is rapid. Many affected children never learn to walk or lose the ability shortly after attaining it. Severe spasticity, progressive cognitive decline, and visual impairment typically result in death during the first decade. Atypical NAD shows more phenotypic variability than INAD. In general, onset is in early childhood but can be as late as the end of the second decade. The presenting signs may be gait instability or ataxia (as in the classic form) or speech delay and autistic features, which are sometimes the only evidence of disease for a year or more. The course is fairly stable during early childhood and resembles static encephalopathy but is followed by neurologic deterioration between ages seven and 12 years. PLA2G6-related dystonia-parkinsonism presents with subacute onset of dystonia-parkinsonism in late adolescence/early adulthood. Other findings are eye movement abnormalities, pyramidal tract signs, and marked cognitive decline.
Huntington disease-like 3
MedGen UID:
347622
Concept ID:
C1858114
Disease or Syndrome
As its name suggests, a Huntington disease-like (HDL) syndrome is a condition that resembles Huntington disease. Researchers have described four HDL syndromes, designated Huntington disease-like 1 (HDL1) through Huntington disease-like 4 (HDL4). These progressive brain disorders are characterized by uncontrolled movements, emotional problems, and loss of thinking ability. HDL syndromes occur in people with the characteristic features of Huntington disease who do not have a mutation in HD, the gene typically associated with that disorder. HDL1, HDL2, and HDL4 usually appear in early to mid-adulthood, although they can begin earlier in life. The first signs and symptoms of these conditions often include irritability, emotional problems, small involuntary movements, poor coordination, and trouble learning new information or making decisions. Many affected people develop involuntary jerking or twitching movements known as chorea. As the disease progresses, these abnormal movements become more pronounced. Affected individuals may develop problems with walking, speaking, and swallowing. People with these disorders also experience changes in personality and a decline in thinking and reasoning abilities. Individuals with an HDL syndrome can live for a few years to more than a decade after signs and symptoms begin. HDL3 begins much earlier in life than most of the other HDL syndromes (usually around age 3 or 4). Affected children experience a decline in thinking ability, difficulties with movement and speech, and seizures. Because HDL3 has a somewhat different pattern of signs and symptoms and a different pattern of inheritance, researchers are unsure whether it belongs in the same category as the other HDL syndromes.
Ataxia-telangiectasia-like disorder
MedGen UID:
348929
Concept ID:
C1858391
Disease or Syndrome
Ataxia-telangiectasia-like disorder-1 is an autosomal recessive disorder characterized clinically by progressive cerebellar degeneration resulting in ataxia and oculomotor apraxia. Laboratory studies of patient cells showed increased susceptibility to radiation, consistent with a defect in DNA repair. The disorder shares some phenotypic features of ataxia-telangiectasia (AT; 208900), but telangiectases and immune deficiency are not present in ATLD1 (summary by Hernandez et al., 1993 and Stewart et al., 1999). Genetic Heterogeneity of Ataxia-Telangiectasia-Like Disorder See also ATLD2 (615919), caused by mutation in the PCNA gene (176740) on chromosome 20p12.
Adult onset ataxia with oculomotor apraxia
MedGen UID:
395301
Concept ID:
C1859598
Disease or Syndrome
Ataxia with oculomotor apraxia type 1 (AOA1) is characterized by childhood onset of slowly progressive cerebellar ataxia, followed by oculomotor apraxia and a severe primary motor peripheral axonal motor neuropathy. The first manifestation is progressive gait imbalance (mean age of onset: 4.3 years; range: 2-10 years), followed by dysarthria, then upper-limb dysmetria with mild intention tremor. Oculomotor apraxia, usually noticed a few years after the onset of ataxia, progresses to external ophthalmoplegia. All affected individuals have generalized areflexia followed by a peripheral neuropathy and quadriplegia with loss of ambulation about seven to ten years after onset. Hands and feet are short and atrophic. Chorea and upper-limb dystonia are common. Intellect remains normal in some individuals; in others, different degrees of cognitive impairment have been observed.
Ataxia-telangiectasia with generalized skin pigmentation and early death
MedGen UID:
395306
Concept ID:
C1859615
Disease or Syndrome
Triosephosphate isomerase deficiency
MedGen UID:
349893
Concept ID:
C1860808
Disease or Syndrome
Triosephosphate isomerase deficiency is an autosomal recessive multisystem disorder characterized by congenital hemolytic anemia, and progressive neuromuscular dysfunction beginning in early childhood. Many patients die from respiratory failure in childhood. The neurologic syndrome is variable, but usually includes lower motor neuron dysfunction with hypotonia, muscle weakness and atrophy, and hyporeflexia. Some patients may show additional signs such as dystonic posturing and/or spasticity. Laboratory studies show intracellular accumulation of dihydroxyacetone phosphate (DHAP), particularly in red blood cells (summary by Fermo et al., 2010).
Amyotrophic dystonic paraplegia
MedGen UID:
354871
Concept ID:
C1862956
Disease or Syndrome
Combined oxidative phosphorylation deficiency 3
MedGen UID:
355842
Concept ID:
C1864840
Disease or Syndrome
Parkinson disease 1
MedGen UID:
357008
Concept ID:
C1868595
Disease or Syndrome
Parkinsonism refers to all clinical states characterized by tremor, muscle rigidity, slowed movement (bradykinesia) and often postural instability. Parkinson disease is the primary and most common form of parkinsonism. Psychiatric manifestations, which include depression and visual hallucinations, are common but not uniformly present. Dementia eventually occurs in at least 20% of cases. The most common sporadic form of Parkinson disease manifests around age 60; however, young-onset and even juvenile presentations are seen.
Parkinson disease 2
MedGen UID:
401500
Concept ID:
C1868675
Disease or Syndrome
Parkin type of early-onset Parkinson disease is characterized by rigidity, bradykinesia, and resting tremor. Lower-limb dystonia may be a presenting sign. Onset usually occurs between ages 20 and 40 years with an average age of onset in the early to mid-thirties. The disease is slowly progressive and disease duration of more than 50 years has been reported. Clinical signs vary; hyperreflexia is common. Dyskinesia as a result of treatment with levodopa frequently occurs.
Ataxia, spastic, 3, autosomal recessive
MedGen UID:
370715
Concept ID:
C1969645
Disease or Syndrome
Ataxia, spastic, 1, autosomal dominant
MedGen UID:
409988
Concept ID:
C1970107
Disease or Syndrome
The hereditary ataxias are a group of genetic disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. In this GeneReview the hereditary ataxias are categorized by mode of inheritance and gene (or chromosomal locus) in which pathogenic variants occur.
Dystonia 19
MedGen UID:
410022
Concept ID:
C1970238
Disease or Syndrome
Familial paroxysmal kinesigenic dyskinesia (referred to as familial PKD in this entry) is characterized by unilateral or bilateral involuntary movements precipitated by other sudden movements such as standing up from a sitting position, being startled, or changes in velocity; attacks include combinations of dystonia, choreoathetosis, and ballism, are sometimes preceded by an aura, and do not involve loss of consciousness. Attacks can be as frequent as 100 per day to as few as one per month. Attacks are usually a few seconds to five minutes in duration but can last several hours. Age of onset, severity and combinations of symptoms vary. Age of onset, typically in childhood and adolescence, ranges from four months to 57 years. The phenotype of PKD can include benign familial infantile epilepsy (BFIE), infantile convulsions and choreoathetosis (ICCA), hemiplegic migraine, migraine with and without aura, and episodic ataxia. Familial PKD is predominantly seen in males.
Choreoathetosis, hypothyroidism, and neonatal respiratory distress
MedGen UID:
369694
Concept ID:
C1970269
Disease or Syndrome
Choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction (CAHTP) is an autosomal dominant disorder characterized by onset of this triad of features in infancy. Movement abnormalities begin with muscular hypotonia followed by the development of chorea, athetosis, dystonia, ataxia, and dysarthria. Some patients show neonatal respiratory distress and developmental delay. The phenotype is variable both between and within families (summary by Thorwarth et al., 2014).
Spastic paraplegia 35
MedGen UID:
393999
Concept ID:
C2676236
Fatty acid hydroxylase-associated neurodegeneration (FAHN) is characterized by central nervous system involvement including corticospinal tract involvement (spasticity), mixed movement disorder (ataxia/dystonia), eye findings (optic atrophy, oculomotor abnormalities) early in the disease course, and progressive intellectual impairment and seizures later in the disease course. FAHN is considered to be a subtype of neurodegeneration with brain iron accumulation (NBIA). To date, a total of 25 individuals from seven families of diverse ethnicity with FAHN have been described; much is yet to be learned about the clinical manifestations and natural history.
Leukodystrophy, hypomyelinating, 6
MedGen UID:
436642
Concept ID:
C2676244
Disease or Syndrome
Hypomyelinating leukodystrophy-6, also known as hypomyelinating leukodystrophy with atrophy of the basal ganglia and cerebellum, is a neurologic disorder characterized by onset in infancy or early childhood of delayed motor development and gait instability, followed by extrapyramidal movement disorders, such as dystonia, choreoathetosis, rigidity, opisthotonus, and oculogyric crises, progressive spastic tetraplegia, ataxia, and, more rarely, seizures. Most patients have cognitive decline and speech delay, but some can function normally. Brain MRI shows a combination of hypomyelination, cerebellar atrophy, and atrophy or disappearance of the putamen. The disorder usually shows sporadic occurrence, but sibs may be affected if a parent is somatic mosaic for the mutation (summary by Simons et al., 2013). Hypomyelinating leukodystrophies (HLD) comprise a genetically heterogeneous entity in which there is a substantial permanent deficit in myelin deposition within the brain, resulting in neurologic deficits (van der Knaap et al., 2002). For a general phenotypic description and a discussion of genetic heterogeneity of hypomyelinating leukodystrophy, see 312080.
Pontocerebellar hypoplasia type 2C
MedGen UID:
382856
Concept ID:
C2676465
Disease or Syndrome
TSEN54-related pontocerebellar hypoplasia (PCH) includes three PCH types (PCH2, 4, and 5) that share characteristic neuroradiologic and neurologic findings. The three types (which differ mainly in life expectancy) were thought to be distinct entities before their molecular basis was known. Children with PCH2 usually succumb before age ten years, whereas those with PCH4 and 5 usually succumb as neonates. Children with PCH2 have generalized clonus, incoordination of sucking and swallowing, impaired motor and cognitive development with lack of voluntary motor development, central visual impairment, and an increased risk for malignant hyperthermia. Epilepsy is present in approximately 50%. Neonates with PCH4 often have seizures, multiple joint contractures (''arthrogryposis''), generalized clonus, and central respiratory impairment. PCH5, which resembles PCH4, has been described in one family.
Cerebroretinal microangiopathy with calcifications and cysts
MedGen UID:
383079
Concept ID:
C2677299
Disease or Syndrome
Cerebroretinal microangiopathy with calcifications and cysts (CRMCC), also known as Coats plus syndrome, is an autosomal recessive pleomorphic disorder characterized primarily by intracranial calcifications, leukodystrophy, and brain cysts, resulting in spasticity, ataxia, dystonia, seizures, and cognitive decline. Patients also have retinal telangiectasia and exudates (Coats disease) as well as extraneurologic manifestations, including osteopenia with poor bone healing and a high risk of gastrointestinal bleeding and portal hypertension caused by vasculature ectasias in the stomach, small intestine, and liver. Some individuals also have hair, skin, and nail changes, as well as anemia and thrombocytopenia (summary by Anderson et al., 2012 and Polvi et al., 2012). Leukoencephalopathy, brain calcifications, and cysts (LCC), also known as Labrune syndrome (614561), has similar central nervous system features as CRMCC in the absence of extraneurologic or systemic manifestations. Although Coats plus syndrome and Labrune syndrome were initially thought to be manifestations of the same disorder, namely CRMCC, molecular evidence has excluded mutations in the CTC1 gene in patients with Labrune syndrome, suggesting that the 2 disorders are not allelic (Anderson et al., 2012; Polvi et al., 2012). Some features of CRMCC resemble those observed in dyskeratosis congenita (see, e.g., 127550), which is a clinically and genetically heterogeneous telomere-related genetic disorder.
Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria)
MedGen UID:
413170
Concept ID:
C2749864
Disease or Syndrome
SUCLA2-related mitochondrial DNA (mtDNA) depletion syndrome is characterized by onset of severe hypotonia in early infancy (birth to five months); severe muscular atrophy with failure to achieve independent ambulation; progressive scoliosis or kyphosis; dystonia and/or hyperkinesias (i.e., athetoid or choreiform movements); epilepsy (infantile spasms or generalized convulsions with onset from birth to three years) in a few children; postnatal growth retardation; and severe sensorineural hearing impairment. The outcome is poor with early lethality.
Hypermanganesemia with dystonia, polycythemia and cirrhosis
MedGen UID:
412958
Concept ID:
C2750442
Disease or Syndrome
The disorder dystonia/parkinsonism, hypermanganesemia, polycythemia, and chronic liver disease is characterized by the following: A movement disorder resulting from manganese accumulation in the basal ganglia. Whole-blood manganese concentrations that often exceed 2000 nmol/L (normal: <320 nmol/L). Polycythemia. Hepatomegaly with variable hepatic fibrosis/cirrhosis. Neurologic findings can manifest either in childhood (ages 2-15 years) as four-limb dystonia, leading to a characteristic high-stepping gait (“cock-walk gait”), dysarthria, fine tremor, and bradykinesia or on occasion spastic paraplegia, or in adulthood as parkinsonism (shuffling gait, rigidity, bradykinesia, hypomimia, and monotone speech) unresponsive to L-dopa treatment. Hepatic failure, secondary complications of cirrhosis, and the neurologic disorder shorten life expectancy.
Parkinson disease 14
MedGen UID:
414488
Concept ID:
C2751842
Disease or Syndrome
Parkinsonism refers to all clinical states characterized by tremor, muscle rigidity, slowed movement (bradykinesia) and often postural instability. Parkinson disease is the primary and most common form of parkinsonism. Psychiatric manifestations, which include depression and visual hallucinations, are common but not uniformly present. Dementia eventually occurs in at least 20% of cases. The most common sporadic form of Parkinson disease manifests around age 60; however, young-onset and even juvenile presentations are seen.
Leukoencephalopathy, cystic, without megalencephaly
MedGen UID:
416646
Concept ID:
C2751843
Disease or Syndrome
Rett syndrome, congenital variant
MedGen UID:
462055
Concept ID:
C3150705
Disease or Syndrome
The congenital variant of Rett syndrome is a severe neurodevelopmental disorder with features of classic Rett syndrome (RTT; 312750), but earlier onset in the first months of life. Classic Rett syndrome shows later onset and is caused by mutation in the MECP2 gene (300005).
Early infantile epileptic encephalopathy 7
MedGen UID:
462336
Concept ID:
C3150986
Disease or Syndrome
EIEE7 is an autosomal dominant seizure disorder characterized by infantile onset of refractory seizures with resultant delayed neurologic development and persistent neurologic abnormalities (Borgatti et al., 2004). EEG initially shows a burst suppression pattern and later evolves to multifocal epileptiform activity. Brain imaging may show lesions in the basal ganglia. Seizures usually remit by age 3 or 4 years, with improvement of EEG abnormalities and possibly brain imaging abnormalities, but the severe neurologic deficits persist (summary by Weckhuysen et al., 2012). Mutation in the KCNQ2 gene can also cause benign familial neonatal seizures-1 (BFNS1; 121200).
Niemann-Pick disease type C1
MedGen UID:
465922
Concept ID:
C3179455
Disease or Syndrome
Niemann-Pick disease type C (NPC) is a lipid storage disease that can present in infants, children, or adults. Neonates can present with ascites and severe liver disease from infiltration of the liver and/or respiratory failure from infiltration of the lungs. Other infants, without liver or pulmonary disease, have hypotonia and developmental delay. The classic presentation occurs in mid-to-late childhood with the insidious onset of ataxia, vertical supranuclear gaze palsy (VSGP), and dementia. Dystonia and seizures are common. Dysarthria and dysphagia eventually become disabling, making oral feeding impossible; death usually occurs in the late second or third decade from aspiration pneumonia. Adults are more likely to present with dementia or psychiatric symptoms.
Amyotrophic lateral sclerosis 15, with or without frontotemporal dementia
MedGen UID:
477090
Concept ID:
C3275459
Disease or Syndrome
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving both upper motor neurons (UMN) and lower motor neurons (LMN). UMN signs include hyperreflexia, extensor plantar response, increased muscle tone, and weakness in a topographic representation. LMN signs include weakness, muscle wasting, hyporeflexia, muscle cramps, and fasciculations. Initial presentation varies. Affected individuals typically present with either asymmetric focal weakness of the extremities (stumbling or poor handgrip) or bulbar findings (dysarthria, dysphagia). Other findings may include muscle fasciculations, muscle cramps, and labile affect, but not necessarily mood. Regardless of initial symptoms, atrophy and weakness eventually affect other muscles. The mean age of onset is 56 years in individuals with no known family history and 46 years in individuals with more than one affected family member (familial ALS or FALS). Average disease duration is about three years, but it can vary significantly. Death usually results from compromise of the respiratory muscles.
SPASTIC PARAPLEGIA 47, AUTOSOMAL RECESSIVE
MedGen UID:
481368
Concept ID:
C3279738
Disease or Syndrome
Microcephaly, cerebellar hypoplasia, and cardiac conduction defect syndrome
MedGen UID:
482322
Concept ID:
C3280692
Disease or Syndrome
The Zaki-Gleeson syndrome is an autosomal recessive neurodevelopmental disorder characterized by profound mental retardation, severe microcephaly, poor growth, cerebellar hypoplasia, and second-degree cardiac conduction defects (summary by Zaki et al., 2011).
THIAMINE METABOLISM DYSFUNCTION SYNDROME 5 (EPISODIC ENCEPHALOPATHY TYPE)
MedGen UID:
482496
Concept ID:
C3280866
Disease or Syndrome
Episodic encephalopathy due to thiamine pyrophosphokinase deficiency is an autosomal recessive metabolic disorder due to an inborn error of thiamine metabolism. The phenotype is highly variable, but in general, affected individuals have onset in early childhood of acute encephalopathic episodes associated with increased serum and CSF lactate. These episodes result in progressive neurologic dysfunction manifest as gait disturbances, ataxia, dystonia, and spasticity, which in some cases may result in loss of ability to walk. Cognitive function is usually preserved, although mildly delayed development has been reported. These episodes are usually associated with infection and metabolic decompensation. Some patients may have recovery of some neurologic deficits (summary by Mayr et al., 2011). For a discussion of genetic heterogeneity of disorders due to thiamine metabolism dysfunction, see THMD1 (249270).
Spastic ataxia 5, autosomal recessive
MedGen UID:
482607
Concept ID:
C3280977
Disease or Syndrome
Spastic ataxia-5 (SPAX5) is an autosomal recessive neurodegenerative disorder characterized by early-onset spasticity resulting in significantly impaired ambulation, cerebellar ataxia, oculomotor apraxia, dystonia, and myoclonic epilepsy (summary by Pierson et al., 2011). For a discussion of genetic heterogeneity of spastic ataxia, see SPAX1 (108600).
Leukoencephalopathy, brain calcifications, and cysts
MedGen UID:
482830
Concept ID:
C3281200
Disease or Syndrome
Leukoencephalopathy, brain calcifications, and cysts (LCC), also known as Labrune syndrome, is characterized by a constellation of features restricted to the central nervous system, including leukoencephalopathy, brain calcifications, and cysts, resulting in spasticity, dystonia, seizures, and cognitive decline (summary by Labrune et al., 1996). See also cerebroretinal microangiopathy with calcifications and cysts (CRMCC; 612199), an autosomal recessive disorder caused by mutation in the CTC1 gene (613129) that shows phenotypic similarities to Labrune syndrome. CRMCC includes the neurologic findings of intracranial calcifications, leukodystrophy, and brain cysts, but also includes retinal vascular abnormalities and other systemic manifestations, such as osteopenia with poor bone healing, a high risk of gastrointestinal bleeding, hair, skin, and nail changes, and anemia and thrombocytopenia. Although Coats plus syndrome and Labrune syndrome were initially thought to be manifestations of the same disorder, namely CRMCC, molecular evidence has excluded mutations in the CTC1 gene in patients with Labrune syndrome, suggesting that the 2 disorders are not allelic (Anderson et al., 2012; Polvi et al., 2012).
Epileptic encephalopathy, early infantile, 1
MedGen UID:
483052
Concept ID:
C3463992
Disease or Syndrome
Early infantile epileptic encephalopathy is a severe form of epilepsy first reported by Ohtahara et al. (1976). It is characterized by frequent tonic seizures or spasms beginning in infancy with a specific EEG finding of suppression-burst patterns, characterized by high-voltage bursts alternating with almost flat suppression phases. Approximately 75% of EIEE patients progress to 'West syndrome,' which is characterized by tonic spasms with clustering, arrest of psychomotor development, and hypsarrhythmia on EEG (Kato et al., 2007). Deprez et al. (2009) reviewed the genetics of epilepsy syndromes starting in the first year of life and included a diagnostic algorithm. EIEE1 is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from lissencephaly (LISX2; 300215) to Proud syndrome (300004) to infantile spasms without brain malformations (EIEE1) to syndromic (309510) and nonsyndromic (300419) mental retardation. Although males with ARX mutations are often more severely affected, female mutation carriers may also be affected (Kato et al., 2004; Wallerstein et al., 2008). Genetic Heterogeneity of Early Infantile Epileptic Encephalopathy EIEE is a genetically heterogeneous disorder. See EIEE2 (300672), caused by mutation in the CDKL5 gene (300203); EIEE3 (609304), caused by mutation in the SLC25A22 gene (609302); EIEE4 (612164), caused by mutation in the STXBP1 gene (602926); EIEE5 (613477), caused by mutation in the SPTAN1 gene (182810); EIEE6 (607208), also known as Dravet syndrome, caused by mutation in the SCN1A gene (182389); EIEE7 (613720), caused by mutation in the KCNQ2 gene (602235); EIEE8 (300607), caused by mutation in the ARHGEF9 gene (300429); EIEE9 (300088), caused by mutation in the PCDH19 gene (300460); EIEE10 (613402), caused by mutation in the PNKP gene (605610); EIEE11 (613721), caused by mutation in the SCN2A gene (182390); EIEE12 (613722), caused by mutation in the PLCB1 gene (607120); EIEE13 (614558), caused by mutation in the SCN8A gene (600702); EIEE14 (614959), caused by mutation in the KCNT1 gene (608167); EIEE15 (615006), caused by mutation in the ST3GAL3 gene (606494); EIEE16 (615338), caused by mutation in the TBC1D24 gene (613577); EIEE17 (615473), caused by mutation in the GNAO1 gene (139311); EIEE18 (615476), caused by mutation in the SZT2 gene (615463); EIEE19 (615744), caused by mutation in the GABRA1 gene (137160); EIEE20 (300868), caused by mutation in the PIGA gene (311770); EIEE21 (615833), caused by mutation in the NECAP1 gene (611623); EIEE22 (300896), caused by mutation in the SLC35A2 gene (314375); EIEE23 (615859), caused by mutation in the DOCK7 gene (615730); EIEE24 (615871), caused by mutation in the HCN1 gene (602780); EIEE25 (615905), caused by mutation in the SLC13A5 gene (608305); EIEE26 (616056), caused by mutation in the KCNB1 gene (600397); EIEE27 (616139), caused by mutation in the GRIN2B gene (138252); and EIEE28 (616211), caused by mutation in the WWOX gene (605131). The phenotype can also be observed in other genetic disorders, including GLUT1 deficiency syndrome (606777); glycine encephalopathy (605899); Aicardi-Goutieres syndrome (225750); and in males with MECP2 mutations (300673), among others. For associations pending confirmation, see MOLECULAR GENETICS.
Aicardi Goutieres syndrome 2
MedGen UID:
483677
Concept ID:
C3489724
Disease or Syndrome
Most characteristically, Aicardi-Goutières syndrome (AGS) manifests as an early-onset encephalopathy that usually, but not always, results in severe intellectual and physical handicap. A subgroup of infants with AGS present at birth with abnormal neurologic findings, hepatosplenomegaly, elevated liver enzymes, and thrombocytopenia, a picture highly suggestive of congenital infection. Otherwise, most affected infants present at variable times after the first few weeks of life, frequently after a period of apparently normal development. Typically, they demonstrate the subacute onset of a severe encephalopathy characterized by extreme irritability, intermittent sterile pyrexias, loss of skills, and slowing of head growth. Over time, as many as 40% develop chilblain skin lesions on the fingers, toes, and ears. It is becoming apparent that atypical, sometimes milder, cases of AGS exist, and thus the true extent of the phenotype associated with mutation of the AGS-related genes is not yet known. For example, mutation of ADAR has recently been associated with a clinical presentation of acute bilateral striatal necrosis.
SPASTIC PARAPLEGIA 53, AUTOSOMAL RECESSIVE
MedGen UID:
761340
Concept ID:
C3539494
Disease or Syndrome
NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 5
MedGen UID:
763887
Concept ID:
C3550973
Disease or Syndrome
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 10
MedGen UID:
766443
Concept ID:
C3553529
Disease or Syndrome
MEGDEL syndrome
MedGen UID:
766511
Concept ID:
C3553597
Disease or Syndrome
ALTERNATING HEMIPLEGIA OF CHILDHOOD 2
MedGen UID:
766702
Concept ID:
C3553788
Disease or Syndrome
Leukoencephalopathy - thalamus and brainstem anomalies - high lactate
MedGen UID:
766993
Concept ID:
C3554079
Disease or Syndrome
COMBINED OXIDATIVE PHOSPHORYLATION DEFICIENCY 13
MedGen UID:
767043
Concept ID:
C3554129
Disease or Syndrome
MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 2
MedGen UID:
767519
Concept ID:
C3554605
Disease or Syndrome
MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 4
MedGen UID:
767521
Concept ID:
C3554607
Disease or Syndrome
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 16
MedGen UID:
815503
Concept ID:
C3809173
Disease or Syndrome
MUSCULAR DYSTROPHY, LIMB-GIRDLE, TYPE 2S
MedGen UID:
815566
Concept ID:
C3809236
Disease or Syndrome
MITOCHONDRIAL DNA DEPLETION SYNDROME 13 (ENCEPHALOMYOPATHIC TYPE)
MedGen UID:
815922
Concept ID:
C3809592
Disease or Syndrome
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 17
MedGen UID:
815936
Concept ID:
C3809606
Disease or Syndrome
PARKINSON DISEASE 19, JUVENILE-ONSET
MedGen UID:
816141
Concept ID:
C3809811
Disease or Syndrome
PARKINSON DISEASE 20, EARLY-ONSET
MedGen UID:
816154
Concept ID:
C3809824
Disease or Syndrome

Recent clinical studies

Etiology

Starr PA, Markun LC, Larson PS, Volz MM, Martin AJ, Ostrem JL
J Neurosurg Pediatr 2014 Oct;14(4):400-8. Epub 2014 Aug 1 doi: 10.3171/2014.6.PEDS13605. [Epub ahead of print] PMID: 25084088
Balint B, Bhatia KP
Curr Opin Neurol 2014 Aug;27(4):468-76. doi: 10.1097/WCO.0000000000000114. PMID: 24978640
Payne S, Tisch S, Cole I, Brake H, Rough J, Darveniza P
Mov Disord 2014 May;29(6):729-35. Epub 2014 Apr 18 doi: 10.1002/mds.25865. [Epub ahead of print] PMID: 24753288
FitzGerald JJ, Rosendal F, de Pennington N, Joint C, Forrow B, Fletcher C, Green AL, Aziz TZ
J Neurol Neurosurg Psychiatry 2014 Dec;85(12):1371-6. Epub 2014 Apr 1 doi: 10.1136/jnnp-2013-306833. [Epub ahead of print] PMID: 24691580
Sattler V, Dickler M, Michaud M, Meunier S, Simonetta-Moreau M
Mov Disord 2014 May;29(6):787-96. Epub 2013 Dec 18 doi: 10.1002/mds.25768. [Epub ahead of print] PMID: 24352854

Diagnosis

Starr PA, Markun LC, Larson PS, Volz MM, Martin AJ, Ostrem JL
J Neurosurg Pediatr 2014 Oct;14(4):400-8. Epub 2014 Aug 1 doi: 10.3171/2014.6.PEDS13605. [Epub ahead of print] PMID: 25084088
Balint B, Bhatia KP
Curr Opin Neurol 2014 Aug;27(4):468-76. doi: 10.1097/WCO.0000000000000114. PMID: 24978640
FitzGerald JJ, Rosendal F, de Pennington N, Joint C, Forrow B, Fletcher C, Green AL, Aziz TZ
J Neurol Neurosurg Psychiatry 2014 Dec;85(12):1371-6. Epub 2014 Apr 1 doi: 10.1136/jnnp-2013-306833. [Epub ahead of print] PMID: 24691580
Michalec M, Hernandez N, Clark LN, Louis ED
Parkinsonism Relat Disord 2014 May;20(5):541-4. Epub 2014 Feb 7 doi: 10.1016/j.parkreldis.2014.01.021. [Epub ahead of print] PMID: 24560600Free PMC Article
de Campos AC, Kukke SN, Hallett M, Alter KE, Damiano DL
J Child Neurol 2014 May;29(5):623-32. Epub 2014 Jan 5 doi: 10.1177/0883073813512523. [Epub ahead of print] PMID: 24396131Free PMC Article

Therapy

Moosavi SM, Ahmadi M, Monajemi MB
Glob J Health Sci 2014 Oct 28;6(6):295-9. doi: 10.5539/gjhs.v6n6p295. PMID: 25363102
Starr PA, Markun LC, Larson PS, Volz MM, Martin AJ, Ostrem JL
J Neurosurg Pediatr 2014 Oct;14(4):400-8. Epub 2014 Aug 1 doi: 10.3171/2014.6.PEDS13605. [Epub ahead of print] PMID: 25084088
Payne S, Tisch S, Cole I, Brake H, Rough J, Darveniza P
Mov Disord 2014 May;29(6):729-35. Epub 2014 Apr 18 doi: 10.1002/mds.25865. [Epub ahead of print] PMID: 24753288
FitzGerald JJ, Rosendal F, de Pennington N, Joint C, Forrow B, Fletcher C, Green AL, Aziz TZ
J Neurol Neurosurg Psychiatry 2014 Dec;85(12):1371-6. Epub 2014 Apr 1 doi: 10.1136/jnnp-2013-306833. [Epub ahead of print] PMID: 24691580
Skogseid IM
Acta Neurol Scand Suppl 2014 Apr;(198):13-9. doi: 10.1111/ane.12231. PMID: 24588501

Prognosis

Starr PA, Markun LC, Larson PS, Volz MM, Martin AJ, Ostrem JL
J Neurosurg Pediatr 2014 Oct;14(4):400-8. Epub 2014 Aug 1 doi: 10.3171/2014.6.PEDS13605. [Epub ahead of print] PMID: 25084088
FitzGerald JJ, Rosendal F, de Pennington N, Joint C, Forrow B, Fletcher C, Green AL, Aziz TZ
J Neurol Neurosurg Psychiatry 2014 Dec;85(12):1371-6. Epub 2014 Apr 1 doi: 10.1136/jnnp-2013-306833. [Epub ahead of print] PMID: 24691580
Haugarvoll K, Tzoulis C, Tran GT, Karlsen B, Engelsen BA, Knappskog PM, Bindoff LA
J Neurol 2014 Feb;261(2):358-62. Epub 2013 Dec 3 doi: 10.1007/s00415-013-7203-9. [Epub ahead of print] PMID: 24297365
Jahanshahi M, Torkamani M, Beigi M, Wilkinson L, Page D, Madeley L, Bhatia K, Hariz M, Zrinzo L, Limousin P, Ruge D, Tisch S
J Neurol 2014 Jan;261(1):164-73. Epub 2013 Nov 1 doi: 10.1007/s00415-013-7161-2. [Epub ahead of print] PMID: 24178706Free PMC Article
Vidailhet M, Jutras MF, Grabli D, Roze E
J Neurol Neurosurg Psychiatry 2013 Sep;84(9):1029-42. Epub 2012 Nov 15 doi: 10.1136/jnnp-2011-301714. [Epub ahead of print] PMID: 23154125

Clinical prediction guides

Starr PA, Markun LC, Larson PS, Volz MM, Martin AJ, Ostrem JL
J Neurosurg Pediatr 2014 Oct;14(4):400-8. Epub 2014 Aug 1 doi: 10.3171/2014.6.PEDS13605. [Epub ahead of print] PMID: 25084088
Payne S, Tisch S, Cole I, Brake H, Rough J, Darveniza P
Mov Disord 2014 May;29(6):729-35. Epub 2014 Apr 18 doi: 10.1002/mds.25865. [Epub ahead of print] PMID: 24753288
FitzGerald JJ, Rosendal F, de Pennington N, Joint C, Forrow B, Fletcher C, Green AL, Aziz TZ
J Neurol Neurosurg Psychiatry 2014 Dec;85(12):1371-6. Epub 2014 Apr 1 doi: 10.1136/jnnp-2013-306833. [Epub ahead of print] PMID: 24691580
Michalec M, Hernandez N, Clark LN, Louis ED
Parkinsonism Relat Disord 2014 May;20(5):541-4. Epub 2014 Feb 7 doi: 10.1016/j.parkreldis.2014.01.021. [Epub ahead of print] PMID: 24560600Free PMC Article
Chung JC, Kim JP, Chang WS, Kim HY, Chang JW
Neuromodulation 2014 Feb;17(2):133-7. Epub 2013 May 17 doi: 10.1111/ner.12077. [Epub ahead of print] PMID: 23682929

Recent systematic reviews

Patel N, Hanfelt J, Marsh L, Jankovic J; members of the Dystonia Coalition
J Neurol Neurosurg Psychiatry 2014 Aug;85(8):882-4. Epub 2014 May 14 doi: 10.1136/jnnp-2013-307316. [Epub ahead of print] PMID: 24828895
Ramos VF, Karp BI, Hallett M
J Neurol Neurosurg Psychiatry 2014 Sep;85(9):987-93. Epub 2014 Jan 31 doi: 10.1136/jnnp-2013-306971. [Epub ahead of print] PMID: 24487380
Galpern WR, Coffey CS, Albanese A, Cheung K, Comella CL, Ecklund DJ, Fahn S, Jankovic J, Kieburtz K, Lang AE, McDermott MP, Shefner JM, Teller JK, Thompson JL, Yeatts SD, Jinnah HA
Neurotherapeutics 2014 Jan;11(1):117-27. doi: 10.1007/s13311-013-0221-6. PMID: 24282121Free PMC Article
Albanese A, Sorbo FD, Comella C, Jinnah HA, Mink JW, Post B, Vidailhet M, Volkmann J, Warner TT, Leentjens AF, Martinez-Martin P, Stebbins GT, Goetz CG, Schrag A
Mov Disord 2013 Jun 15;28(7):874-83. doi: 10.1002/mds.25579. PMID: 23893443Free PMC Article
Vidailhet M, Jutras MF, Grabli D, Roze E
J Neurol Neurosurg Psychiatry 2013 Sep;84(9):1029-42. Epub 2012 Nov 15 doi: 10.1136/jnnp-2011-301714. [Epub ahead of print] PMID: 23154125

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