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Chorea

MedGen UID:
3420
Concept ID:
C0008489
Disease or Syndrome
Synonym: Choreatic disease
SNOMED CT: Chorea (271700006); Choreiform movement (271700006); Choreic movement (271700006); Choreiform disorder (271700006)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
HPO: HP:0002072
Monarch Initiative: MONDO:0001595
Orphanet: ORPHA1429

Definition

Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion. It is a random-appearing sequence of one or more discrete involuntary movements or movement fragments. Movements appear random because of variability in timing, duration or location. Each movement may have a distinct start and end. However, movements may be strung together and thus may appear to flow randomly from one muscle group to another. Chorea can involve the trunk, neck, face, tongue, and extremities. [from HPO]

Conditions with this feature

Huntington disease
MedGen UID:
5654
Concept ID:
C0020179
Disease or Syndrome
Huntington disease (HD) is a progressive disorder of motor, cognitive, and psychiatric disturbances. The mean age of onset is 35 to 44 years, and the median survival time is 15 to 18 years after onset.
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, juvenile MLD, and adult MLD. Age of onset within a family is usually similar. The disease course may be from several years in the late-infantile-onset form to decades in the juvenile- and adult-onset forms. Late-infantile MLD. Onset is before age 30 months. Typical presenting findings include weakness, hypotonia, clumsiness, frequent falls, toe walking, and dysarthria. As the disease progresses, language, cognitive, and gross and fine motor skills regress. Later signs include spasticity, pain, seizures, and compromised vision and hearing. In the final stages, children have tonic spasms, decerebrate posturing, and general unawareness of their surroundings. Juvenile MLD. Onset is between age 30 months and 16 years. Initial manifestations include decline in school performance and emergence of behavioral problems, followed by gait disturbances. Progression is similar to but slower than in the late-infantile form. Adult MLD. Onset occurs after age 16 years, sometimes not until the fourth or fifth decade. Initial signs can include problems in school or job performance, personality changes, emotional lability, or psychosis; in others, neurologic symptoms (weakness and loss of coordination progressing to spasticity and incontinence) or seizures initially predominate. 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 earlier-onset forms.
Tay-Sachs disease, variant AB
MedGen UID:
78657
Concept ID:
C0268275
Disease or Syndrome
Acute infantile GM2 activator deficiency is a neurodegenerative disorder in which infants, who are generally normal at birth, have progressive weakness and slowing of developmental progress between ages four and 12 months. An ensuing developmental plateau is followed by progressively rapid developmental regression. By the second year of life decerebrate posturing, difficulty in swallowing, and worsening seizures lead to an unresponsive vegetative state. Death usually occurs between ages two and three years.
Acetyl-CoA acetyltransferase-2 deficiency
MedGen UID:
90995
Concept ID:
C0342735
Disease or Syndrome
Benign hereditary chorea
MedGen UID:
98278
Concept ID:
C0393584
Disease or Syndrome
NKX2-1-related disorders range from benign hereditary chorea (BHC) to choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress (also known as brain-lung-thyroid syndrome). Childhood-onset chorea, the hallmark of NKX2-1-related disorders, may or may not be associated with respiratory distress syndrome or congenital hypothyroidism. Chorea generally begins in early infancy or about age one year (most commonly) or in late childhood or adolescence, and progresses into the second decade after which it remains static or (rarely) remits. Pulmonary disease, the second most common manifestation, can include respiratory distress syndrome in neonates, interstitial lung disease in young children, and pulmonary fibrosis in older persons. The risk for pulmonary carcinoma is increased in young adults with an NKX2-1-related disorder. Thyroid dysfunction, the result of dysembryogenesis, can present as congenital hypothyroidism or compensated hypothyroidism. The risk for thyroid cancer is unknown and may not be increased. In one review, 50% of affected individuals had the full brain-lung-thyroid syndrome, 30% had involvement of brain and thyroid only, and 13% had isolated chorea only.
McLeod neuroacanthocytosis syndrome
MedGen UID:
140765
Concept ID:
C0398568
Disease or Syndrome
McLeod neuroacanthocytosis syndrome (designated as MLS throughout this review) is a multisystem disorder with central nervous system (CNS), neuromuscular, cardiovascular, and hematologic manifestations in males: CNS manifestations are a neurodegenerative basal ganglia disease including movement disorders, cognitive alterations, and psychiatric symptoms. Neuromuscular manifestations include a (mostly subclinical) sensorimotor axonopathy and muscle weakness or atrophy of different degrees. Cardiac manifestations include dilated cardiomyopathy, atrial fibrillation, and tachyarrhythmia. Hematologically, MLS is defined as a specific blood group phenotype (named after the first proband, Hugh McLeod) that results from absent expression of the Kx erythrocyte antigen and weakened expression of Kell blood group antigens. The hematologic manifestations are red blood cell acanthocytosis and compensated hemolysis. Alloantibodies in the Kell and Kx blood group system can cause strong reactions to transfusions of incompatible blood and severe anemia in affected male newborns of Kell-negative mothers. Females heterozygous for XK pathogenic variants have mosaicism for the Kell and Kx blood group antigens. Although they usually lack CNS and neuromuscular manifestations, some heterozygous females may develop clinical manifestations including chorea or late-onset cognitive decline.
Deletion of long arm of chromosome 18
MedGen UID:
96605
Concept ID:
C0432443
Disease or Syndrome
Monosomy 18q is a partial deletion of the long arm of chromosome 18 characterized by highly variable phenotype, most commonly including hypotonia, developmental delay, short stature, growth hormone deficiency, hearing loss and external ear anomalies, intellectual disability, palatal defects, dysmorphic facial features, skeletal anomalies (foot deformities, tapering fingers, scoliosis) and mood disorders.
3-Methylglutaconic aciduria type 3
MedGen UID:
108273
Concept ID:
C0574084
Disease or Syndrome
Costeff syndrome is characterized by optic atrophy and/or choreoathetoid movement disorder with onset before age ten years. Optic atrophy is associated with progressive decrease in visual acuity within the first years of life, sometimes associated with infantile-onset horizontal nystagmus. Most individuals have chorea, often severe enough to restrict ambulation. Some are confined to a wheelchair from an early age. Although most individuals develop spastic paraparesis, mild ataxia, and occasional mild cognitive deficit in their second decade, the course of the disease is relatively stable.
Dentatorubral-pallidoluysian atrophy
MedGen UID:
155630
Concept ID:
C0751781
Disease or Syndrome
Dentatorubral-pallidoluysian atrophy (DRPLA) is a progressive disorder of ataxia, myoclonus, epilepsy, and progressive intellectual deterioration in children and ataxia, choreoathetosis, and dementia or character changes in adults. Onset ranges from before age one year to age 72 years; mean age of onset is 31.5 years. The clinical presentation varies depending on the age of onset. The cardinal features in adults are ataxia, choreoathetosis, and dementia. Cardinal features in children are progressive intellectual deterioration, behavioral changes, myoclonus, and epilepsy.
Spinocerebellar ataxia type 1
MedGen UID:
155703
Concept ID:
C0752120
Disease or Syndrome
Spinocerebellar ataxia type 1 (SCA1) is characterized by progressive cerebellar ataxia, dysarthria, and eventual deterioration of bulbar functions. Early in the disease, affected individuals may have gait disturbance, slurred speech, difficulty with balance, brisk deep tendon reflexes, hypermetric saccades, nystagmus, and mild dysphagia. Later signs include slowing of saccadic velocity, development of up-gaze palsy, dysmetria, dysdiadochokinesia, and hypotonia. In advanced stages, muscle atrophy, decreased deep tendon reflexes, loss of proprioception, cognitive impairment (e.g., frontal executive dysfunction, impaired verbal memory), chorea, dystonia, and bulbar dysfunction are seen. Onset is typically in the third or fourth decade, although childhood onset and late-adult onset have been reported. Those with onset after age 60 years may manifest a pure cerebellar phenotype. Interval from onset to death varies from ten to 30 years; individuals with juvenile onset show more rapid progression and more severe disease. Anticipation is observed. An axonal sensory neuropathy detected by electrophysiologic testing is common; brain imaging typically shows cerebellar and brain stem atrophy.
Spinocerebellar ataxia 7
MedGen UID:
156006
Concept ID:
C0752125
Disease or Syndrome
Spinocerebellar ataxia type 7 (SCA7) comprises a phenotypic spectrum ranging from adolescent- or adult-onset progressive cerebellar ataxia and cone-rod retinal dystrophy to infantile or early-childhood onset with multiorgan failure, an accelerated course, and early death. Anticipation in this nucleotide repeat disorder may be so dramatic that within a family a child with infantile or early-childhood onset may be diagnosed with what is thought to be an unrelated neurodegenerative disorder years before a parent or grandparent with a CAG repeat expansion becomes symptomatic. In adolescent-onset SCA7, the initial manifestation is typically impaired vision, followed by cerebellar ataxia. In those with adult onset, progressive cerebellar ataxia usually precedes the onset of visual manifestations. While the rate of progression varies in these two age groups, the eventual result for almost all affected individuals is loss of vision, severe dysarthria and dysphagia, and a bedridden state with loss of motor control.
Methylmalonic acidemia with homocystinuria, type cblX
MedGen UID:
167111
Concept ID:
C0796208
Disease or Syndrome
Disorders of intracellular cobalamin metabolism have a variable phenotype and age of onset that are influenced by the severity and location within the pathway of the defect. The prototype and best understood phenotype is cblC; it is also the most common of these disorders. The age of initial presentation of cblC spans a wide range: In utero with fetal presentation of nonimmune hydrops, cardiomyopathy, and intrauterine growth restriction. Newborns, who can have microcephaly, poor feeding, and encephalopathy. Infants, who can have poor feeding and slow growth, neurologic abnormality, and, rarely, hemolytic uremic syndrome (HUS). Toddlers, who can have poor growth, progressive microcephaly, cytopenias (including megaloblastic anemia), global developmental delay, encephalopathy, and neurologic signs such as hypotonia and seizures. Adolescents and adults, who can have neuropsychiatric symptoms, progressive cognitive decline, thromboembolic complications, and/or subacute combined degeneration of the spinal cord.
Deficiency of ferroxidase
MedGen UID:
168057
Concept ID:
C0878682
Disease or Syndrome
Aceruloplasminemia is characterized by iron accumulation in the brain and viscera. The clinical triad of retinal degeneration, diabetes mellitus (DM), and neurologic disease is seen in individuals ranging from age 30 years to older than 70 years. The neurologic findings of movement disorder (blepharospasm, grimacing, facial and neck dystonia, tremors, chorea) and ataxia (gait ataxia, dysarthria) correspond to regions of iron deposition in the brain. Individuals with aceruloplasminemia often present with anemia prior to onset of DM or obvious neurologic problems. Cognitive dysfunction including apathy and forgetfulness occurs in more than half of individuals with this condition.
Chorea, remitting, with nystagmus and cataract
MedGen UID:
330463
Concept ID:
C1832422
Disease or Syndrome
Striatonigral degeneration, infantile, mitochondrial
MedGen UID:
374113
Concept ID:
C1839022
Disease or Syndrome
X-linked dystonia-parkinsonism
MedGen UID:
326820
Concept ID:
C1839130
Disease or Syndrome
Individuals with X-linked dystonia-parkinsonism (XDP) have dystonia of varying severity and parkinsonism. XDP afflicts primarily Filipino men and, rarely, women. The mean age of onset in men is 39 years; the clinical course is highly variable with parkinsonism as the initial presenting sign, overshadowed by dystonia as the disease progresses. Features of parkinsonism include resting tremor, bradykinesia, rigidity, postural instability, and severe shuffling gait. The dystonia develops focally, most commonly in the jaw, neck, trunk, and eyes, and less commonly in the limbs, tongue, pharynx, and larynx, the most characteristic being jaw dystonia often progressing to neck dystonia. Individuals with pure parkinsonism have non-disabling symptoms that are only slowly progressive; those who develop a combination of parkinsonism and dystonia can develop multifocal or generalized symptoms within a few years and die prematurely from pneumonia or intercurrent infections. Female carriers are mostly asymptomatic, though a small minority may manifest dystonia, parkinsonism, or chorea.
Cataract, congenital, with mental impairment and dentate gyrus atrophy
MedGen UID:
334365
Concept ID:
C1843257
Disease or Syndrome
Biotin-responsive basal ganglia disease
MedGen UID:
375289
Concept ID:
C1843807
Disease or Syndrome
Biotin-thiamine-responsive basal ganglia disease (BTBGD) may present in childhood, early infancy, or adulthood. The classic presentation of BTBGD occurs in childhood (age 3-10 years) and 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 stress. Simple partial or generalized seizures are easily controlled with anti-seizure medication. An early-infantile Leigh-like syndrome / atypical infantile spasms presentation occurs in the first three months of life with poor feeding, vomiting, acute encephalopathy, and severe lactic acidosis. An adult-onset Wernicke-like encephalopathy presentation is characterized by acute onset of status epilepticus, ataxia, nystagmus, diplopia, and ophthalmoplegia in the second decade of life. Prompt administration of biotin and thiamine early in the disease course results in partial or complete improvement within days in the childhood and adult presentations, but most with the infantile presentation have had poor outcome even after supplementation with biotin and thiamine.
Syndromic X-linked intellectual disability Lubs type
MedGen UID:
337496
Concept ID:
C1846058
Disease or Syndrome
MECP2 duplication syndrome is a severe neurodevelopmental disorder characterized by early-onset hypotonia, feeding difficulty, gastrointestinal manifestations including gastroesophageal reflux and constipation, delayed psychomotor development leading to severe intellectual disability, poor speech development, progressive spasticity, recurrent respiratory infections (in ~75% of affected individuals), and seizures (in ~50%). MECP2 duplication syndrome is 100% penetrant in males. Occasionally females have been described with a MECP2 duplication and a range of findings from mild intellectual disability to a phenotype similar to that seen in males. In addition to the core features, autistic behaviors, nonspecific neuroradiologic findings on brain MRI, mottled skin, and urogenital anomalies have been observed in several affected boys.
Spinocerebellar ataxia type 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.
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 which lead to death within ten to 20 years. HDL2 cannot be differentiated from Huntington disease clinically. Neurologic abnormalities include chorea, hypokinesia (rigidity, bradykinesia), dysarthria, and hyperreflexia in the later stages of the disease. There is a strong correlation between the duration of the disease and the progression of the motor and cognitive disorder.
Pontocerebellar hypoplasia type 2A
MedGen UID:
376379
Concept ID:
C1848526
Disease or Syndrome
TSEN54 pontocerebellar hypoplasia (TSEN54-PCH) comprises three PCH phenotypes (PCH2, 4, and 5) that share characteristic neuroradiologic and neurologic findings. The three PCH phenotypes (which differ mainly in life expectancy) were considered to be distinct entities before their molecular basis was known. PCH2. Children usually succumb before age ten years (those with PCH4 and 5 usually succumb as neonates). Children with PCH2 have generalized clonus, uncoordinated sucking and swallowing, impaired cognitive development, lack of voluntary motor development, cortical blindness, and an increased risk for rhabdomyolysis during severe infections. Epilepsy is present in approximately 50%. PCH4. Neonates often have seizures, multiple joint contractures ("arthrogryposis"), generalized clonus, and central respiratory impairment. PCH5 resembles PCH4 and has been described in one family.
Neuroferritinopathy
MedGen UID:
381211
Concept ID:
C1853578
Disease or Syndrome
Neuroferritinopathy is an adult-onset progressive movement disorder characterized by chorea or dystonia and speech and swallowing deficits. The movement disorder typically affects one or two limbs and progresses to become more generalized within 20 years of disease onset. When present, asymmetry in the movement abnormalities remains throughout the course of the disorder. Most individuals develop a characteristic orofacial action-specific dystonia related to speech that leads to dysarthrophonia. Frontalis overactivity and orolingual dyskinesia are common. Cognitive deficits and behavioral issues become major problems with time.
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2
MedGen UID:
340052
Concept ID:
C1853761
Disease or Syndrome
Ataxia with oculomotor apraxia type 2 (AOA2) is characterized by onset of ataxia between age three and 30 years after initial normal development, axonal sensorimotor neuropathy, oculomotor apraxia, cerebellar atrophy, and elevated serum concentration of alpha-fetoprotein (AFP).
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: Infantile neuroaxonal dystrophy (INAD). Atypical neuroaxonal dystrophy (atypical NAD). PLA2G6-related dystonia-parkinsonism. INAD usually begins between ages six months and three years with psychomotor regression or delay, hypotonia, and progressive spastic tetraparesis. Many affected children never learn to walk or lose the ability shortly after attaining it. Strabismus, nystagmus, and optic atrophy are common. Disease progression is rapid, resulting in severe spasticity, progressive cognitive decline, and visual impairment. Many affected children do not survive beyond their 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, ataxia, or speech delay and autistic features, which are sometimes the only evidence of disease for a year or more. Strabismus, nystagmus, and optic atrophy are common. Neuropsychiatric disturbances including impulsivity, poor attention span, hyperactivity, and emotional lability are also common. 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 has a variable age of onset, but most individuals present in early adulthood with gait disturbance or neuropsychiatric changes. Affected individuals consistently develop dystonia and parkinsonism (which may be accompanied by rapid cognitive decline) in their late teens to early twenties. Dystonia is most common in the hands and feet but may be more generalized. The most common features of parkinsonism in these individuals are bradykinesia, resting tremor, rigidity, and postural instability.
Huntington disease-like 3
MedGen UID:
347622
Concept ID:
C1858114
Disease or Syndrome
A rare Huntington disease-like syndrome with characteristics of childhood-onset progressive neurologic deterioration with pyramidal and extrapyramidal abnormalities, chorea, dystonia, ataxia, gait instability, spasticity, seizures, mutism, and (on brain MRI) progressive frontal cortical atrophy and bilateral caudate atrophy.
Congenital cataracts-facial dysmorphism-neuropathy syndrome
MedGen UID:
346973
Concept ID:
C1858726
Congenital Abnormality
CTDP1-related congenital cataracts, facial dysmorphism, and neuropathy (CTDP1-CCFDN) is characterized by abnormalities of the eye (bilateral congenital cataracts, microcornea, microphthalmia, micropupils), mildly dysmorphic facial features apparent in late childhood, and a hypo-/demyelinating, symmetric, distal peripheral neuropathy. The neuropathy is predominantly motor at the onset and results in delays in early motor development, progressing to severe disability by the third decade of life. Secondary foot deformities and scoliosis are common. Sensory neuropathy develops after age ten years. Most affected individuals have a mild nonprogressive intellectual deficit and cerebellar involvement including ataxia, nystagmus, intention tremor, and dysmetria. All have short stature and most have subnormal weight. Adults have hypogonadotropic hypogonadism. Parainfectious rhabdomyolysis (profound muscle weakness, myoglobinuria, and excessively elevated serum concentration of creatine kinase usually following a viral infection) is a potentially life-threatening complication. To date all affected individuals and carriers identified have been from the Romani population.
Chorea, benign familial
MedGen UID:
347799
Concept ID:
C1859098
Disease or Syndrome
Benign hereditary chorea (BHC) is a rare movement disorder that beginsin infancy or childhood. Signs and symptoms in infants may include low muscle tone, involuntary movements (chorea), lung infections, and respiratory distress. Signs and symptoms in children may include delayed motor and walking milestones, jerky muscle movements (myoclonus), upper limb dystonia, motor tics, and vocal tics. The chorea often improves with time. In some cases, myoclonus persists or worsens. Children with BHC can havenormal intellect, but may have learning and behavior problems. Other signs and symptoms include thyroid problems (e.g., hypothyroidism) and lung disease (e.g., recurring infections). Treatment is tailored to each child. Tetrabenazine and levodopa have been tried in individual cases with some success. BHC is caused by mutations in the NKX2-1 gene (also known as the TITF1 gene). It is passed through families in an autosomal dominant fashion.
Cerebellar ataxia-hypogonadism syndrome
MedGen UID:
349137
Concept ID:
C1859305
Disease or Syndrome
PNPLA6 disorders span a phenotypic continuum characterized by variable combinations of cerebellar ataxia; upper motor neuron involvement manifesting as spasticity and/or brisk reflexes; chorioretinal dystrophy associated with variable degrees of reduced visual function; and hypogonadotropic hypogonadism (delayed puberty and lack of secondary sex characteristics). The hypogonadotropic hypogonadism occurs either in isolation or as part of anterior hypopituitarism (growth hormone, thyroid hormone, or gonadotropin deficiencies). Common but less frequent features are peripheral neuropathy (usually of axonal type manifesting as reduced distal reflexes, diminished vibratory sensation, and/or distal muscle wasting); hair anomalies (long eyelashes, bushy eyebrows, or scalp alopecia); short stature; and impaired cognitive functioning (learning disabilities in children; deficits in attention, visuospatial abilities, and recall in adults). Some of these features can occur in distinct clusters on the phenotypic continuum: Boucher-Neuhäuser syndrome (cerebellar ataxia, chorioretinal dystrophy, and hypogonadotropic hypogonadism); Gordon Holmes syndrome (cerebellar ataxia, hypogonadotropic hypogonadism, and – to a variable degree – brisk reflexes); Oliver-McFarlane syndrome (trichomegaly, chorioretinal dystrophy, short stature, intellectual disability, and hypopituitarism); Laurence-Moon syndrome; and spastic paraplegia type 39 (SPG39) (upper motor neuron involvement, peripheral neuropathy, and sometimes reduced cognitive functioning and/or cerebellar ataxia).
Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia
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.
Huntington disease-like 1
MedGen UID:
355137
Concept ID:
C1864112
Disease or Syndrome
Genetic prion disease generally manifests with cognitive difficulties, ataxia, and myoclonus (abrupt jerking movements of muscle groups and/or entire limbs). The order of appearance and/or predominance of these features and other associated neurologic and psychiatric findings vary. The three major phenotypes of genetic prion disease are genetic Creutzfeldt-Jakob disease (gCJD), fatal familial insomnia (FFI), and Gerstmann-Sträussler-Scheinker (GSS) syndrome. Although these phenotypes display overlapping clinical and pathologic features, recognition of these phenotypes can be useful when providing affected individuals and their families with information about the expected clinical course. The age at onset typically ranges from 50 to 60 years. The disease course ranges from a few months in gCJD and FFI to a few (up to 4, and in rare cases up to 10) years in GSS syndrome.
Cataract 11 multiple types
MedGen UID:
351162
Concept ID:
C1864567
Disease or Syndrome
Mutations in the PITX3 gene have been found to cause multiple types of cataract, which have been described as congenital total and posterior polar. The preferred title/symbol for this entry was formerly 'Cataract, Posterior Polar, 4; CTPP4.'
Episodic kinesigenic dyskinesia 2
MedGen UID:
410022
Concept ID:
C1970238
Disease or Syndrome
A dystonia characterized by autosomal dominant inheritance of recurrent brief involuntary hyperkinesias triggered by sudden movements that has material basis in variation in the chromosome region 16q13-q22.1.
Pontocerebellar hypoplasia type 2C
MedGen UID:
382856
Concept ID:
C2676465
Disease or Syndrome
TSEN54 pontocerebellar hypoplasia (TSEN54-PCH) comprises three PCH phenotypes (PCH2, 4, and 5) that share characteristic neuroradiologic and neurologic findings. The three PCH phenotypes (which differ mainly in life expectancy) were considered to be distinct entities before their molecular basis was known. PCH2. Children usually succumb before age ten years (those with PCH4 and 5 usually succumb as neonates). Children with PCH2 have generalized clonus, uncoordinated sucking and swallowing, impaired cognitive development, lack of voluntary motor development, cortical blindness, and an increased risk for rhabdomyolysis during severe infections. Epilepsy is present in approximately 50%. PCH4. Neonates often have seizures, multiple joint contractures ("arthrogryposis"), generalized clonus, and central respiratory impairment. PCH5 resembles PCH4 and has been described in one family.
Pontocerebellar hypoplasia type 2B
MedGen UID:
393505
Concept ID:
C2676466
Disease or Syndrome
TSEN54 pontocerebellar hypoplasia (TSEN54-PCH) comprises three PCH phenotypes (PCH2, 4, and 5) that share characteristic neuroradiologic and neurologic findings. The three PCH phenotypes (which differ mainly in life expectancy) were considered to be distinct entities before their molecular basis was known. PCH2. Children usually succumb before age ten years (those with PCH4 and 5 usually succumb as neonates). Children with PCH2 have generalized clonus, uncoordinated sucking and swallowing, impaired cognitive development, lack of voluntary motor development, cortical blindness, and an increased risk for rhabdomyolysis during severe infections. Epilepsy is present in approximately 50%. PCH4. Neonates often have seizures, multiple joint contractures ("arthrogryposis"), generalized clonus, and central respiratory impairment. PCH5 resembles PCH4 and has been described in one family.
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).
Pontocerebellar hypoplasia type 2D
MedGen UID:
462490
Concept ID:
C3151140
Disease or Syndrome
PCH2D is an autosomal recessive disorder characterized by progressive microcephaly, postnatal onset of progressive atrophy of the cerebrum and cerebellum, profound mental retardation, spasticity, and variable seizures (summary by Ben-Zeev et al., 2003). For a general phenotypic description and a discussion of genetic heterogeneity of pontocerebellar hypoplasia type 2, see PCH2A (277470).
Intellectual disability, autosomal dominant 6
MedGen UID:
462761
Concept ID:
C3151411
Mental or Behavioral Dysfunction
GRIN2B-related neurodevelopmental disorder is characterized by mild to profound developmental delay / intellectual disability (DD/ID) in all affected individuals. Muscle tone abnormalities (spasticity and/or hypotonia, occasionally associated with feeding difficulties), as well as epilepsy and autism spectrum disorder (ASD) / behavioral issues, are common. Other infantile- or childhood-onset findings include microcephaly; dystonic, dyskinetic, or choreiform movement disorder; and/or cortical visual impairment. Brain MRI reveals a malformation of cortical development in a minority of affected individuals. To date, fewer than 100 individuals with GRIN2B-related neurodevelopmental disorder have been reported.
Intellectual disability, autosomal dominant 8
MedGen UID:
481912
Concept ID:
C3280282
Disease or Syndrome
GRIN1-related neurodevelopmental disorder (GRIN1-NDD) is characterized by mild-to-profound developmental delay / intellectual disability (DD/ID) in all affected individuals. Other common manifestations are epilepsy, muscular hypotonia, movement disorders, spasticity, feeding difficulties, and behavior problems. A subset of individuals show a malformation of cortical development consisting of extensive and diffuse bilateral polymicrogyria. To date, 72 individuals with GRIN1-NDD have been reported.
Pontocerebellar hypoplasia type 8
MedGen UID:
767123
Concept ID:
C3554209
Disease or Syndrome
Pontocerebellar hypoplasia type 8 is an autosomal recessive neurodevelopmental disorder characterized by severe psychomotor retardation, abnormal movements, hypotonia, spasticity, and variable visual defects. Brain MRI shows pontocerebellar hypoplasia, decreased cerebral white matter, and a thin corpus callosum (summary by Mochida et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1 (607596).
Developmental and epileptic encephalopathy, 17
MedGen UID:
815936
Concept ID:
C3809606
Disease or Syndrome
Developmental and epileptic encephalopathy-17 (DEE17) is a severe neurologic disorder characterized by onset of intractable seizures in the first weeks or months of life. EEG often shows a burst-suppression pattern consistent with a clinical diagnosis of Ohtahara syndrome. Affected infants have very poor psychomotor development and may have brain abnormalities, such as cerebral atrophy or thin corpus callosum. Some patients may show involuntary movements (summary by Nakamura et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
Basal ganglia calcification, idiopathic, 5
MedGen UID:
815975
Concept ID:
C3809645
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 a gradually progressive movement disorder and neuropsychiatric symptoms. The movement disorder first manifests as clumsiness, fatigability, unsteady gait, slow or slurred speech, dysphagia, involuntary movements, or muscle cramping. 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. Seizures of various types occur frequently, some individuals experience chronic headache and vertigo; urinary urgency or incontinence may be present.
Proximal myopathy with extrapyramidal signs
MedGen UID:
816615
Concept ID:
C3810285
Disease or Syndrome
Myopathy with extrapyramidal signs is an autosomal recessive disorder characterized by early childhood onset of proximal muscle weakness and learning disabilities. While the muscle weakness is static, most patients develop progressive extrapyramidal signs that may become disabling (summary by Logan et al., 2014). Brain MRI in 1 patient showed congenital malformations, including polymicrogyria and cerebellar dysplasia (Wilton et al., 2020).
Ataxia-telangiectasia-like disorder 1
MedGen UID:
861227
Concept ID:
C4012790
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.
Developmental and epileptic encephalopathy, 27
MedGen UID:
863753
Concept ID:
C4015316
Disease or Syndrome
GRIN2B-related neurodevelopmental disorder is characterized by mild to profound developmental delay / intellectual disability (DD/ID) in all affected individuals. Muscle tone abnormalities (spasticity and/or hypotonia, occasionally associated with feeding difficulties), as well as epilepsy and autism spectrum disorder (ASD) / behavioral issues, are common. Other infantile- or childhood-onset findings include microcephaly; dystonic, dyskinetic, or choreiform movement disorder; and/or cortical visual impairment. Brain MRI reveals a malformation of cortical development in a minority of affected individuals. To date, fewer than 100 individuals with GRIN2B-related neurodevelopmental disorder have been reported.
Autoinflammatory syndrome, familial, Behcet-like 1
MedGen UID:
898541
Concept ID:
C4225218
Disease or Syndrome
Familial Behcet-like autoinflammatory syndrome-1 (AIFBL1) is an autosomal dominant monogenic autoinflammatory disease characterized predominantly by painful and recurrent mucosal ulceration affecting the oral mucosa, gastrointestinal tract, and genital areas. The onset of symptoms is usually in the first decade, although later onset has been reported. Additional more variable features include skin rash, uveitis, and polyarthritis, consistent with a systemic hyperinflammatory state. Many patients have evidence of autoimmune disease. Rare patients may also have concurrent features of immunodeficiency, including recurrent infections with low numbers of certain white blood cells or impaired function of immune cells. The disorder results from a failure of mutant TNFAIP3 to suppress the activation of inflammatory cytokines in the NFKB (see 164011) signaling pathway; treatment with tumor necrosis factor (TNFA; 191160) inhibitors may be beneficial. Although some of the clinical features of AIFBL1 resemble those of Behcet disease (109650), the more common form of Behcet disease is believed to be polygenic, typically shows later onset in early adulthood, and has symptoms usually restricted to the mucosa (summary by Zhou et al., 2016; Aeschlimann et al., 2018, and Kadowaki et al., 2018). Genetic Heterogeneity of AIFBL See also AIFBL2 (301074), caused by mutation in the ELF4 gene (300775) on chromosome Xq26, and AIFBL3 (618287), caused by mutation in the RELA gene (164014) on chromosome 11q13.
Developmental and epileptic encephalopathy, 29
MedGen UID:
908570
Concept ID:
C4225361
Disease or Syndrome
Developmental and epileptic encephalopathy-29 (DEE29) is an autosomal recessive neurologic disorder characterized by the onset of refractory myoclonic seizures in the first months of life. Affected individuals have poor overall growth, congenital microcephaly with cerebral atrophy and impaired myelination on brain imaging, spasticity with abnormal movements, peripheral neuropathy, and poor visual fixation (summary by Simons et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities
MedGen UID:
934601
Concept ID:
C4310634
Disease or Syndrome
MECR-related neurologic disorder is characterized by a progressive childhood-onset movement disorder and optic atrophy; intellect is often – but not always – preserved. The movement disorder typically presents between ages one and 6.5 years and is mainly dystonia that can be accompanied by chorea and/or ataxia. Over time some affected individuals require assistive devices for mobility. Speech fluency and intelligibility are progressively impaired due to dysarthria. Optic atrophy typically develops between ages four and 12 years and manifests as reduced visual acuity, which can include functional blindness (also known as legal blindness) in adulthood. Because only 13 affected individuals are known to the authors, and because nearly half of them were diagnosed retrospectively as adults, the natural history of disease progression and other aspects of the phenotype have not yet been completely defined.
Myoclonus, intractable, neonatal
MedGen UID:
934625
Concept ID:
C4310658
Disease or Syndrome
Neonatal intractable myoclonus (NEIMY) is a severe neurologic disorder characterized by the onset of intractable myoclonic seizures soon after birth. Affected infants have intermittent apnea, abnormal eye movements, pallor of the optic nerve, and lack of developmental progress. Brain imaging shows a progressive leukoencephalopathy. Some patients may die in infancy. There is phenotypic and biochemical evidence of mitochondrial dysfunction (summary by Duis et al., 2016).
Developmental and epileptic encephalopathy, 37
MedGen UID:
934737
Concept ID:
C4310770
Disease or Syndrome
Developmental and epileptic encephalopathy-37 (DEE37) is an autosomal recessive epileptic-dyskinetic neurologic disorder characterized by the onset of intractable seizures or abnormal movements in the first months or years of life. Patients typically have normal or only mildly delayed development in early infancy, but then show developmental regression and stagnation after the onset of seizures, which can occur between about 6 months to 2 years of age. In addition to epileptic encephalopathy, affected individuals also manifest a hyperkinetic movement disorder with choreoathetosis, spasticity, and rigidity. There is severely impaired intellectual development and function, loss of verbal skills with absent speech, and impaired volitional movements (summary by Madeo et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
Chorea, childhood-onset, with psychomotor retardation
MedGen UID:
934754
Concept ID:
C4310787
Disease or Syndrome
Striatal degeneration, autosomal dominant 2
MedGen UID:
934758
Concept ID:
C4310791
Disease or Syndrome
Autosomal dominant striatal degeneration-2 is a neurologic disorder characterized by hyperkinetic movements, mainly chorea, resulting from dysfunction of the basal ganglia. Although symptoms appear in the first decade, the disorder is not progressive (summary by Mencacci et al., 2016). For a discussion of genetic heterogeneity of ADSD, see ADSD1 (609161).
Neurodevelopmental disorder with involuntary movements
MedGen UID:
1374697
Concept ID:
C4479569
Disease or Syndrome
NEDIM is a neurodevelopmental and neurodegenerative disorder characterized by delayed psychomotor development and infantile or childhood onset of hyperkinetic involuntary movements, including chorea and athetosis. The abnormal movements can be severe, sometimes resulting in inability to sit, walk, speak, or eat. Hyperkinetic movements can be exacerbated by specific triggers, such as stress, illness, or high temperature. Some patients have brain abnormalities, such as cerebral atrophy or thin corpus callosum, and some patients may develop seizures (summary by Ananth et al., 2016 and Danti et al., 2017).
Autosomal recessive limb-girdle muscular dystrophy type R18
MedGen UID:
1385598
Concept ID:
C4517996
Disease or Syndrome
Autosomal recessive limb-girdle muscular dystrophy-18 (LGMD18) is characterized by childhood-onset of proximal muscle weakness resulting in gait abnormalities and scapular winging. Serum creatine kinase is increased. A subset of patients may show a hyperkinetic movement disorder with chorea, ataxia, or dystonia and global developmental delay (summary by Bogershausen et al., 2013). Additional more variable features include alacrima, achalasia, cataracts, or hepatic steatosis (Liang et al., 2015; Koehler et al., 2017). For a discussion of genetic heterogeneity of autosomal recessive limb-girdle muscular dystrophy, see LGMDR1 (253600).
Intellectual disability, autosomal dominant 45
MedGen UID:
1616472
Concept ID:
C4539848
Mental or Behavioral Dysfunction
Childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder
MedGen UID:
1626007
Concept ID:
C4540086
Disease or Syndrome
Childhood-onset neurodegeneration with brain atrophy (CONDBA) is a severe progressive neurodegenerative disorder characterized by loss of motor and cognitive skills between ages 2 and 7 years. Affected individuals may have normal development or mild developmental delay, but all eventually lose all motor skills, resulting in inability to walk, absence of language, and profound intellectual disability. Brain imaging shows progressive cerebral and cerebellar atrophy (summary by Edvardson et al., 2017).
Neurodevelopmental disorder with severe motor impairment and absent language
MedGen UID:
1622162
Concept ID:
C4540496
Mental or Behavioral Dysfunction
NEDMIAL is a neurodevelopmental disorder characterized by delayed psychomotor development and hypotonia apparent from early infancy, resulting in feeding difficulties, ataxic gait or inability to walk, delayed or absent speech development, and impaired intellectual development, sometimes with behavioral abnormalities, such as hand-flapping. Additional common features may include sleep disorder, nonspecific dysmorphic facial features, and joint hyperlaxity (summary by Lessel et al., 2017 and Mannucci et al., 2021).
Idiopathic basal ganglia calcification 1
MedGen UID:
1637664
Concept ID:
C4551624
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 a gradually progressive movement disorder and neuropsychiatric symptoms. The movement disorder first manifests as clumsiness, fatigability, unsteady gait, slow or slurred speech, dysphagia, involuntary movements, or muscle cramping. 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. Seizures of various types occur frequently, some individuals experience chronic headache and vertigo; urinary urgency or incontinence may be present.
Neurodevelopmental disorder with or without seizures and gait abnormalities
MedGen UID:
1645968
Concept ID:
C4693391
Disease or Syndrome
Neurodevelopmental disorder with or without seizures and gait abnormalities (NEDSGA) is an autosomal dominant disorder characterized by global developmental delay apparent from infancy or early childhood, resulting in variably impaired intellectual development that can range from profound with absent speech to mild with an ability to attend special schools. Most affected individuals show irritability, stiffness, and hypertonia early in life, which progresses to spasticity and impaired gait later. Some patients may develop seizures of variable severity early in life (summary by Martin et al., 2017).
Spinocerebellar ataxia 47
MedGen UID:
1636349
Concept ID:
C4693672
Disease or Syndrome
Spinocerebellar ataxia-47 (SCA47) is an autosomal dominant neurologic disorder characterized by slowly progressive gait ataxia. Additional features usually include diplopia, dysarthria, and dysmetria. Brain imaging shows atrophy of the cerebellar vermis. The age at onset is variable: affected members in 1 reported family developed symptoms as adults in their thirties or forties, whereas 1 unrelated girl had onset in the first decade (Gennarino et al., 2018). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).
Developmental and epileptic encephalopathy, 64
MedGen UID:
1633501
Concept ID:
C4693899
Disease or Syndrome
Developmental and epileptic encephalopathy-64 (DEE64) is a neurodevelopmental disorder characterized by onset of seizures usually in the first year of life and associated with intellectual disability, poor motor development, and poor or absent speech. Additional features include hypotonia, abnormal movements, and nonspecific dysmorphic features. The severity is variable: some patients are unable to speak, walk, or interact with others as late as the teenage years, whereas others may have some comprehension (summary by Straub et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
Spinocerebellar ataxia 48
MedGen UID:
1648409
Concept ID:
C4748158
Disease or Syndrome
SCA48 is an autosomal dominant neurodegenerative disorder characterized by onset of gait ataxia and/or cognitive-affective symptoms in midadulthood. Patients may present with involvement of either system, but most eventually develop impairment in both. Features include gait ataxia, dysarthria, and dysphagia, as well as cognitive decline, deficits in executive function, and psychiatric or affective manifestations, such as depression, anxiety, and apathy. Additional more variable features may include movement abnormalities, such as parkinsonism, tremor, chorea, dystonia, and dysmetria; spasticity is not observed. Brain imaging shows selective atrophy of the posterior areas of the cerebellar vermis, often with bilateral T2-weighted hyperintensities in the dentate nuclei (the 'crab sign'), and diffusion tensor imaging (DTI) may show paucity of cerebellar connections to the brainstem and cerebrum. The presentation is consistent with a clinical diagnosis of cerebellar cognitive-affective syndrome (CCAS). The phenotype shows both inter- and intrafamilial variability as well as some clinical overlap with SCAR16, suggesting that mutations in the STUB1 gene result in a spectrum of neurodegenerative manifestations (summary by Genis et al., 2018; Cocozza et al., 2020; Palvadeau et al., 2020; Ravel et al., 2021). Magri et al. (2022) found evidence that heterozygous STUB1 variants alone do not cause disease but require a concurrent expanded repeat allele of the TBP gene (600075) for disease manifestation; see MOLECULAR GENETICS.
Basal ganglia calcification, idiopathic, 7, autosomal recessive
MedGen UID:
1683911
Concept ID:
C5193025
Disease or Syndrome
Autosomal recessive idiopathic basal ganglia calcification-7 is a neurologic disorder characterized by onset of symptoms in adulthood. Patients present with dysarthria, gait abnormalities, various movement abnormalities, and often cognitive decline. Brain imaging shows abnormal accumulation of calcium deposits in deep brain regions, including the basal ganglia, thalamus, dentate nuclei, cerebellum, and sometimes other areas of the brain and spinal cord. Some patients with brain imaging abnormalities may be clinically asymptomatic (summary by Yao et al., 2018). For a detailed phenotypic description and a discussion of genetic heterogeneity of IBGC, see IBGC1 (213600).
NAD(P)HX dehydratase deficiency
MedGen UID:
1681210
Concept ID:
C5193026
Disease or Syndrome
Early-onset progressive encephalopathy with brain edema and/or leukoencephalopathy-2 (PEBEL2) is an autosomal recessive severe neurometabolic disorder characterized by rapidly progressive neurologic deterioration that is usually associated with a febrile illness. Affected infants tend to show normal early development followed by acute psychomotor regression with ataxia, hypotonia, and sometimes seizures, resulting in death in the first years of life. Brain imaging shows multiple abnormalities, including brain edema and signal abnormalities in the cortical and subcortical regions (summary by Van Bergen et al., 2019). For a discussion of genetic heterogeneity of PEBEL, see PEBEL1 (617186).
Neurodevelopmental disorder with impaired speech and hyperkinetic movements
MedGen UID:
1681181
Concept ID:
C5193088
Disease or Syndrome
Neurodevelopmental disorder with impaired speech and hyperkinetic movements (NEDISHM) is an autosomal recessive disorder characterized by global developmental delay apparent in infancy. Most patients have mildly delayed walking, speech and language delay, and a hyperkinetic movement disorder with dystonia, tremor, ataxia, or chorea. Some may develop seizures that tend to abate (summary by Khan et al., 2019).
Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia
MedGen UID:
1676579
Concept ID:
C5193104
Disease or Syndrome
Early-onset neurodegeneration with choreoathetoid movements and microcytic anemia (NDCAMA) is an autosomal recessive disorder characterized by severe psychomotor developmental abnormalities, abnormal movements, and functional iron deficiency (Costain et al., 2019).
Cerebellar atrophy with seizures and variable developmental delay
MedGen UID:
1683734
Concept ID:
C5193132
Disease or Syndrome
Cerebellar atrophy with seizures and variable developmental delay (CASVDD) is an autosomal recessive neurologic disorder characterized by cerebellar ataxia associated with atrophy of the cerebellar vermis on brain imaging. Most patients also have onset of severe refractory seizures in the first year of life and show global developmental delay, compatible with epileptic encephalopathy (summary by Edvardson et al., 2013). However, at least 1 patient with normal cognitive development and only 1 febrile seizure has been reported (Valence et al., 2019), suggesting significant clinical variability of this disorder.
Developmental and epileptic encephalopathy, 78
MedGen UID:
1684724
Concept ID:
C5231409
Disease or Syndrome
Developmental and epileptic encephalopathy-78 (DEE78) is a severe neurologic disorder characterized by onset of refractory seizures in the first days or months of life followed by severely impaired intellectual development. Additional features may include cortical visual impairment, hypotonia, and abnormal movements, such as spasticity (summary by Butler et al., 2018). One family with an attenuated disease course has been reported (Maljevic et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
Mitochondrial DNA depletion syndrome 17
MedGen UID:
1684823
Concept ID:
C5231412
Disease or Syndrome
Mitochondrial complex 5 (ATP synthase) deficiency, nuclear type 6
MedGen UID:
1684729
Concept ID:
C5231461
Disease or Syndrome
Mitochondrial complex V (ATP synthase) deficiency nuclear type 6 (MC5DN6) is an autosomal recessive progressive and degenerative disorder characterized by episodic regression of gross motor skills beginning in early childhood. The episodes are associated with metabolic stress, including fever, illness, and general anesthesia. Patients develop gait difficulties or loss of ambulation, as well as other variable abnormalities, including abnormal movements, hemiplegia, and persistent lethargy. Brain imaging shows degenerative features in the basal ganglia and brainstem consistent with a diagnosis of Leigh syndrome (see 256000) (summary by Barca et al., 2018). For a discussion of genetic heterogeneity of mitochondrial complex V deficiency, see MC5DN1 (604273).
Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements
MedGen UID:
1684874
Concept ID:
C5231491
Disease or Syndrome
Neurodevelopmental disorder with hypotonia and autistic features with or without hyperkinetic movements (NEDHAHM) is characterized by axial hypotonia apparent from birth, global developmental delay with impaired intellectual development and poor or absent language acquisition, and behavioral abnormalities, including autistic features, poor social interaction, and hang-wringing. Most patients have childhood-onset seizures that are usually responsive to medication, and a subset of patients develop cortical visual impairment and involuntary hyperkinetic movements, including chorea and dystonia. Some of the features are reminiscent of Rett syndrome (RTT; 312750) (summary by Salpietro et al., 2019).
Intellectual developmental disorder 60 with seizures
MedGen UID:
1684702
Concept ID:
C5231497
Disease or Syndrome
Autosomal dominant intellectual developmental disorder-60 with seizures is characterized by global developmental delay apparent in infancy, followed by onset of seizures in the first years of life. Patients have delayed walking, an ataxic gait, and moderately to severely impaired intellectual development with poor speech (summary by Helbig et al., 2019).
Developmental and epileptic encephalopathy, 84
MedGen UID:
1720141
Concept ID:
C5394081
Disease or Syndrome
Developmental and epileptic encephalopathy-84 (DEE84) is an autosomal recessive neurologic disorder characterized by onset of refractory seizures in the first months or years of life. Affected individuals have severely impaired global development with impaired intellectual development, absent speech, and inability to walk. Other features include axial hypotonia, peripheral spasticity, feeding difficulties that sometimes necessitate tube feeding, and mild dysmorphic facial features. Brain imaging may show nonspecific findings such as cerebral/cerebellar atrophy and/or hypomyelination. The severity of the disorder is variable (summary by Hengel et al., 2020). For a discussion of genetic heterogeneity of DEE, see 308350.
Neurodevelopmental disorder with relative macrocephaly and with or without cardiac or endocrine anomalies
MedGen UID:
1714169
Concept ID:
C5394221
Disease or Syndrome
Nabais Sa-de Vries syndrome type 2 (NSDVS2) is characterized by global developmental delay apparent from birth and distinctive dysmorphic facial features. Most patients have additional anomalies, including congenital heart defects, sleep disturbances, hypotonia, and variable endocrine abnormalities, such as hypothyroidism (summary by Nabais Sa et al., 2020).
Neurodevelopmental disorder with language impairment and behavioral abnormalities
MedGen UID:
1708389
Concept ID:
C5394502
Disease or Syndrome
Neurodevelopmental disorder with speech impairment and behavioral abnormalities (NEDLIB) is characterized by impaired intellectual development or developmental delay, behavioral abnormalities including autistic features, and language impairment. Other features include seizures and developmental regression (Salpietro et al., 2019).
Intellectual developmental disorder with paroxysmal dyskinesia or seizures
MedGen UID:
1727046
Concept ID:
C5436894
Disease or Syndrome
Intellectual developmental disorder with paroxysmal dyskinesia or seizures (IDDPADS) is an autosomal recessive complex neurologic disorder characterized by global developmental delay with impaired intellectual development and language delay. In addition, most patients develop a paroxysmal hyperkinetic movement disorder in the first months or years of life manifest as sudden falls or backward propulsion, eye or head deviation, and dystonic limb posturing followed by chorea and dyskinetic movements. The episodes are pharmacoresistant to anticonvulsant medication. EEG may show interictal abnormalities, but are usually not consistent with epilepsy. However, some patients may also develop epileptic seizures or only have seizures without a movement disorder (summary by Doummar et al., 2020).
Cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome
MedGen UID:
1780242
Concept ID:
C5543287
Disease or Syndrome
CIMDAG syndrome (CIMDAG) is a multisystemic disorder characterized by severely impaired psychomotor development and hematologic abnormalities apparent from early infancy. Affected individuals show poor overall growth with microcephaly, impaired intellectual development, poor or absent speech, poor eye contact, and motor problems, such as inability to walk, hypotonia, and spasticity. Brain imaging typically shows cerebral and cerebellar atrophy, thin corpus callosum, and delayed myelination. The associated hematologic abnormalities are variable, but are mostly consistent with congenital dyserythropoietic anemia (CDA) (summary by Rodger et al., 2020 and Seu et al., 2020).
Developmental and epileptic encephalopathy 6B
MedGen UID:
1779648
Concept ID:
C5543353
Disease or Syndrome
SCN1A seizure disorders encompass a spectrum that ranges from simple febrile seizures and generalized epilepsy with febrile seizures plus (GEFS+) at the mild end to Dravet syndrome and intractable childhood epilepsy with generalized tonic-clonic seizures (ICE-GTC) at the severe end. Phenotypes with intractable seizures including Dravet syndrome are often associated with cognitive decline. Less commonly observed phenotypes include myoclonic astatic epilepsy (MAE), Lennox-Gastaut syndrome, infantile spasms, epilepsy with focal seizures, and vaccine-related encephalopathy and seizures. The phenotype of SCN1A seizure disorders can vary even within the same family.
Dyskinesia with orofacial involvement, autosomal dominant
MedGen UID:
1790407
Concept ID:
C5551343
Disease or Syndrome
ADCY5 dyskinesia is a hyperkinetic movement disorder (more prominent in the face and arms than the legs) characterized by infantile to late-adolescent onset of chorea, athetosis, dystonia, myoclonus, or a combination of these. To date, affected individuals have had overlapping (but not identical) manifestations with wide-ranging severity. The facial movements are typically periorbital and perioral. The dyskinesia is prone to episodic or paroxysmal exacerbation lasting minutes to hours, and may occur during sleep. Precipitating factors in some persons have included emotional stress, intercurrent illness, sneezing, or caffeine; in others, no precipitating factors have been identified. In some children, severe infantile axial hypotonia results in gross motor delays accompanied by chorea, sometimes with language delays. The overall tendency is for the abnormal movements to stabilize in early middle age, at which point they may improve in some individuals; less commonly, the abnormal movements are slowly progressive, increasing in severity and frequency.
Ritscher-Schinzel syndrome 4
MedGen UID:
1794149
Concept ID:
C5561939
Disease or Syndrome
Ritscher-Schinzel syndrome-4 (RTSC4) is characterized by a constellation of congenital anomalies, including dysmorphic craniofacial features and structural brain anomalies, such as Dandy-Walker malformation (220200), hindbrain malformations, or agenesis of the corpus callosum, associated with global developmental delay and impaired intellectual development. Congenital cardiac defects have been reported in 1 family (summary by Ritscher et al., 1987 and Jeanne et al., 2021). For a discussion of genetic heterogeneity of Ritscher-Schinzel syndrome, see RTSC1 (220210).
Infantile-onset generalized dyskinesia with orofacial involvement
MedGen UID:
1798887
Concept ID:
C5567464
Disease or Syndrome
Infantile-onset limb and orofacial dyskinesia is an autosomal recessive neurologic disorder characterized by delayed motor development and onset of a hyperkinetic movement disorder in the first year of life. The disorder results in impaired walking and orofacial dyskinesia with difficulty talking; the severity is variable (summary by Diggle et al., 2016).
Combined oxidative phosphorylation defect type 27
MedGen UID:
1799031
Concept ID:
C5567608
Disease or Syndrome
Combined oxidative phosphorylation deficiency-27 (COXPD27) is an autosomal recessive multisystem disorder characterized mainly by neurologic features, including delayed development, seizures, abnormal movements, and neurologic regression. Age at onset, ranging from infancy to late childhood, and severity are variable. Other features include hypotonia, myoclonus, brain imaging abnormalities, and evidence of mitochondrial dysfunction in skeletal muscle. Liver dysfunction has also been reported (summary by Samanta et al., 2018). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Systemic lupus erythematosus 17
MedGen UID:
1804329
Concept ID:
C5676884
Disease or Syndrome
Systemic lupus erythematosus-17 (SLE17) is an X-linked dominant autoimmune disorder characterized by onset of systemic autoinflammatory symptoms in the first decades of life. Only affected females have been reported. Features may include classic features of SLE, such as malar rash and arthralgias, or can include less common entities such as hemiplegia and neuromyelitis optica (NMO). Laboratory studies show the presence of autoantibodies and enhanced NFKB (164011) signaling, the latter being consistent with a gain-of-function effect (Brown et al., 2022). For a phenotypic description and a discussion of genetic heterogeneity of systemic lupus erythematosus (SLE), see 152700.
Neurodevelopmental disorder with or without variable movement or behavioral abnormalities
MedGen UID:
1802087
Concept ID:
C5676908
Disease or Syndrome
Neurodevelopmental disorder with or without variable movement or behavioral abnormalities (NEDMAB) is an autosomal dominant disorder characterized by mildly to severely impaired intellectual development and, in some patients, movement abnormalities consisting of tremors, cerebellar ataxia, or extrapyramidal symptoms. Movement abnormalities have onset in childhood or adolescence. Other variable features include autism spectrum disorder or autistic features and epilepsy.
Parkinsonism-dystonia 3, childhood-onset
MedGen UID:
1808365
Concept ID:
C5676913
Disease or Syndrome
Childhood-onset parkinsonism-dystonia-3 (PKDYS3) is an autosomal recessive neurodegenerative disorder with onset in infancy or early childhood. Affected individuals present with progressive movement abnormalities, including parkinsonism with tremor, dystonia, myoclonus ataxia, and hyperkinetic movements such as ballismus. The parkinsonism features may be responsive to treatment with levodopa, although many patients develop levodopa-induced dyskinesia. Some patients may have mild cognitive impairment or psychiatric disturbances (summary by Burke et al., 2018 and Skorvanek et al., 2022). For a discussion of genetic heterogeneity of PKDYS, see 613135.
Developmental and epileptic encephalopathy 100
MedGen UID:
1809351
Concept ID:
C5676932
Disease or Syndrome
Developmental and epileptic encephalopathy-100 (DEE100) is a severe neurologic disorder characterized by global developmental delay and onset of variable types of seizures in the first months or years of life. Most patients have refractory seizures and show developmental regression after seizure onset. Affected individuals have ataxic gait or inability to walk and severe to profoundly impaired intellectual development, often with absent speech. Additional more variable features may include axial hypotonia, hyperkinetic movements, dysmorphic facial features, and brain imaging abnormalities (summary by Schneider et al., 2021). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.
Neurodevelopmental disorder with dystonia and seizures
MedGen UID:
1804461
Concept ID:
C5677004
Disease or Syndrome
Neurodevelopmental disorder with dystonia and seizures (NEDDS) is a severe autosomal recessive disorder characterized by hypotonia and dystonic posturing apparent from early infancy. Affected individuals show global developmental delay with inability to walk or speak and have profoundly impaired intellectual development, often with behavioral abnormalities. Additional features may include other extrapyramidal movements, seizures or seizure-like activity, and cerebellar hypoplasia on brain imaging (Sleiman et al., 2022).
Classic dopamine transporter deficiency syndrome
MedGen UID:
1814585
Concept ID:
C5700336
Disease or Syndrome
SLC6A3-related dopamine transporter deficiency syndrome (DTDS) is a complex movement disorder with a continuum that ranges from classic early-onset DTDS (in the first 6 months) to atypical later-onset DTDS (in childhood, adolescence, or adulthood). Classic DTDS. Infants typically manifest nonspecific findings (irritability, feeding difficulties, axial hypotonia, and/or delayed motor development) followed by a hyperkinetic movement disorder (with features of chorea, dystonia, ballismus, orolingual dyskinesia). Over time, affected individuals develop parkinsonism-dystonia characterized by bradykinesia (progressing to akinesia), dystonic posturing, distal tremor, rigidity, and reduced facial expression. Limitation of voluntary movements leads to severe motor delay. Episodic status dystonicus, exacerbations of dystonia, and secondary orthopedic, gastrointestinal, and respiratory complications are common. Many affected individuals appear to show relative preservation of intellect with good cognitive development. Atypical DTDS. Normal psychomotor development in infancy and early childhood is followed by later-onset manifestations of parkinsonism-dystonia with tremor, progressive bradykinesia, variable tone, and dystonic posturing. The long-term outcome of this form is currently unknown.
Neurodevelopmental disorder with poor growth, spastic tetraplegia, and hearing loss
MedGen UID:
1824002
Concept ID:
C5774229
Disease or Syndrome
Birk-Aharoni syndrome (BKAH) is a severe neurodevelopmental disorder characterized developmental delay, impaired intellectual development, absent speech, spastic tetraplegia with central hypotonia, chorea, inability to walk, hearing loss, micropenis, undescended testes, and mildly elevated liver enzymes (Aharoni et al., 2022).
Developmental and epileptic encephalopathy 110
MedGen UID:
1824038
Concept ID:
C5774265
Disease or Syndrome
Developmental and epileptic encephalopathy-110 (DEE110) is an autosomal recessive disorder characterized by profound global developmental delay and hypotonia apparent in infancy followed by onset of seizures in the first months or years of life. Affected individuals achieve almost no developmental milestones and show impaired intellectual development, poor or absent speech, inability to walk or grasp objects, peripheral spasticity, and poor eye contact. Brain imaging shows hypoplastic corpus callosum and cortical atrophy (Dahimene et al., 2022). For a discussion of genetic heterogeneity of DEE, see 308350.
Spinocerebellar ataxia 50
MedGen UID:
1824045
Concept ID:
C5774272
Disease or Syndrome
Spinocerebellar ataxia-50 (SCA50) is an autosomal dominant neurologic disorder characterized by cerebellar ataxia, oculomotor apraxia and other eye movement abnormalities, and cerebellar atrophy on brain imaging. Most patients develop symptoms as adults, although childhood onset has rarely been reported. Additional more variable features may include tremor, dysarthria, dysphagia, and cognitive impairment with executive dysfunction (Coutelier et al., 2022; Schoggl et al., 2022).
Congenital disorder of deglycosylation 1
MedGen UID:
989503
Concept ID:
CN306977
Disease or Syndrome
Individuals with NGLY1-related congenital disorder of deglycosylation (NGLY1-CDDG) typically display a clinical tetrad of developmental delay / intellectual disability in the mild to profound range, hypo- or alacrima, elevated liver transaminases that may spontaneously resolve in childhood, and a complex hyperkinetic movement disorder that can include choreiform, athetoid, dystonic, myoclonic, action tremor, and dysmetric movements. About half of affected individuals will develop clinical seizures. Other findings may include obstructive and/or central sleep apnea, oral motor defects that affect feeding ability, auditory neuropathy, constipation, scoliosis, and peripheral neuropathy.

Professional guidelines

PubMed

Stoker TB, Mason SL, Greenland JC, Holden ST, Santini H, Barker RA
Pract Neurol 2022 Feb;22(1):32-41. Epub 2021 Aug 19 doi: 10.1136/practneurol-2021-003074. PMID: 34413240
Baizabal-Carvallo JF, Cardoso F
J Neural Transm (Vienna) 2020 Oct;127(10):1323-1342. Epub 2020 Aug 9 doi: 10.1007/s00702-020-02238-3. PMID: 32776155
Uthman I, Noureldine MHA, Ruiz-Irastorza G, Khamashta M
Ann Rheum Dis 2019 Feb;78(2):155-161. Epub 2018 Oct 3 doi: 10.1136/annrheumdis-2018-213846. PMID: 30282668

Recent clinical studies

Etiology

Ghosh R, Roy D, Dubey S, Das S, Benito-León J
Tremor Other Hyperkinet Mov (N Y) 2022;12:14. Epub 2022 May 4 doi: 10.5334/tohm.671. PMID: 35601204Free PMC Article
Teixeira AL, Vasconcelos LP, Nunes MDCP, Singer H
Expert Rev Neurother 2021 Aug;21(8):913-922. Epub 2021 Aug 18 doi: 10.1080/14737175.2021.1965883. PMID: 34353207
Brandsma R, van Egmond ME, Tijssen MAJ; Groningen Movement Disorder Expertise Centre
Dev Med Child Neurol 2021 Mar;63(3):252-258. Epub 2020 Nov 5 doi: 10.1111/dmcn.14721. PMID: 33150968Free PMC Article
Pandey S
J Assoc Physicians India 2013 Jul;61(7):471-4, 483. PMID: 24772751
Roos RA
Orphanet J Rare Dis 2010 Dec 20;5:40. doi: 10.1186/1750-1172-5-40. PMID: 21171977Free PMC Article

Diagnosis

Stimming EF, Bega D
Continuum (Minneap Minn) 2022 Oct 1;28(5):1379-1408. doi: 10.1212/CON.0000000000001169. PMID: 36222771
Baizabal-Carvallo JF, Cardoso F
J Neural Transm (Vienna) 2020 Oct;127(10):1323-1342. Epub 2020 Aug 9 doi: 10.1007/s00702-020-02238-3. PMID: 32776155
Termsarasab P
Continuum (Minneap Minn) 2019 Aug;25(4):1001-1035. doi: 10.1212/CON.0000000000000763. PMID: 31356291
McGuire S, Chanchani S, Khurana DS
Semin Pediatr Neurol 2018 Apr;25:75-81. Epub 2017 Dec 27 doi: 10.1016/j.spen.2017.12.007. PMID: 29735119
Cardoso F
J Neurol Neurosurg Psychiatry 2017 May;88(5):412-417. Epub 2016 Dec 1 doi: 10.1136/jnnp-2016-314475. PMID: 27919056

Therapy

Stimming EF, Bega D
Continuum (Minneap Minn) 2022 Oct 1;28(5):1379-1408. doi: 10.1212/CON.0000000000001169. PMID: 36222771
Stoker TB, Mason SL, Greenland JC, Holden ST, Santini H, Barker RA
Pract Neurol 2022 Feb;22(1):32-41. Epub 2021 Aug 19 doi: 10.1136/practneurol-2021-003074. PMID: 34413240
Baizabal-Carvallo JF, Cardoso F
J Neural Transm (Vienna) 2020 Oct;127(10):1323-1342. Epub 2020 Aug 9 doi: 10.1007/s00702-020-02238-3. PMID: 32776155
Bashir H, Jankovic J
Expert Rev Neurother 2018 Jan;18(1):51-63. Epub 2017 Nov 15 doi: 10.1080/14737175.2018.1403899. PMID: 29120264
Huntington Study Group, Frank S, Testa CM, Stamler D, Kayson E, Davis C, Edmondson MC, Kinel S, Leavitt B, Oakes D, O'Neill C, Vaughan C, Goldstein J, Herzog M, Snively V, Whaley J, Wong C, Suter G, Jankovic J, Jimenez-Shahed J, Hunter C, Claassen DO, Roman OC, Sung V, Smith J, Janicki S, Clouse R, Saint-Hilaire M, Hohler A, Turpin D, James RC, Rodriguez R, Rizer K, Anderson KE, Heller H, Carlson A, Criswell S, Racette BA, Revilla FJ, Nucifora F Jr, Margolis RL, Ong M, Mendis T, Mendis N, Singer C, Quesada M, Paulsen JS, Brashers-Krug T, Miller A, Kerr J, Dubinsky RM, Gray C, Factor SA, Sperin E, Molho E, Eglow M, Evans S, Kumar R, Reeves C, Samii A, Chouinard S, Beland M, Scott BL, Hickey PT, Esmail S, Fung WL, Gibbons C, Qi L, Colcher A, Hackmyer C, McGarry A, Klos K, Gudesblatt M, Fafard L, Graffitti L, Schneider DP, Dhall R, Wojcieszek JM, LaFaver K, Duker A, Neefus E, Wilson-Perez H, Shprecher D, Wall P, Blindauer KA, Wheeler L, Boyd JT, Houston E, Farbman ES, Agarwal P, Eberly SW, Watts A, Tariot PN, Feigin A, Evans S, Beck C, Orme C, Edicola J, Christopher E
JAMA 2016 Jul 5;316(1):40-50. doi: 10.1001/jama.2016.8655. PMID: 27380342

Prognosis

Vreeland A, Thienemann M, Cunningham M, Muscal E, Pittenger C, Frankovich J
Psychiatr Clin North Am 2023 Mar;46(1):69-88. doi: 10.1016/j.psc.2022.11.004. PMID: 36740356
Farag M, Hunt BJ, Andrews TC
Pract Neurol 2023 Apr;23(2):150-152. Epub 2022 Oct 7 doi: 10.1136/pn-2022-003587. PMID: 36207127
Stimming EF, Bega D
Continuum (Minneap Minn) 2022 Oct 1;28(5):1379-1408. doi: 10.1212/CON.0000000000001169. PMID: 36222771
Defebvre L, Krystkowiak P
Rev Neurol (Paris) 2016 Aug-Sep;172(8-9):483-487. Epub 2016 Jul 28 doi: 10.1016/j.neurol.2016.07.006. PMID: 27476417
Pringsheim T, Wiltshire K, Day L, Dykeman J, Steeves T, Jette N
Mov Disord 2012 Aug;27(9):1083-91. Epub 2012 Jun 12 doi: 10.1002/mds.25075. PMID: 22692795

Clinical prediction guides

Pérez-Dueñas B, Gorman K, Marcé-Grau A, Ortigoza-Escobar JD, Macaya A, Danti FR, Barwick K, Papandreou A, Ng J, Meyer E, Mohammad SS, Smith M, Muntoni F, Munot P, Uusimaa J, Vieira P, Sheridan E, Guerrini R, Cobben J, Yilmaz S, De Grandis E, Dale RC, Pons R, Peall KJ, Leuzzi V, Kurian MA
Mov Disord 2022 Nov;37(11):2197-2209. Epub 2022 Aug 25 doi: 10.1002/mds.29182. PMID: 36054588Free PMC Article
Bologna M, Valls-Solè J, Kamble N, Pal PK, Conte A, Guerra A, Belvisi D, Berardelli A
Clin Neurophysiol 2022 Aug;140:110-125. Epub 2022 Jun 8 doi: 10.1016/j.clinph.2022.05.014. PMID: 35785630
Huntington Study Group, Frank S, Testa CM, Stamler D, Kayson E, Davis C, Edmondson MC, Kinel S, Leavitt B, Oakes D, O'Neill C, Vaughan C, Goldstein J, Herzog M, Snively V, Whaley J, Wong C, Suter G, Jankovic J, Jimenez-Shahed J, Hunter C, Claassen DO, Roman OC, Sung V, Smith J, Janicki S, Clouse R, Saint-Hilaire M, Hohler A, Turpin D, James RC, Rodriguez R, Rizer K, Anderson KE, Heller H, Carlson A, Criswell S, Racette BA, Revilla FJ, Nucifora F Jr, Margolis RL, Ong M, Mendis T, Mendis N, Singer C, Quesada M, Paulsen JS, Brashers-Krug T, Miller A, Kerr J, Dubinsky RM, Gray C, Factor SA, Sperin E, Molho E, Eglow M, Evans S, Kumar R, Reeves C, Samii A, Chouinard S, Beland M, Scott BL, Hickey PT, Esmail S, Fung WL, Gibbons C, Qi L, Colcher A, Hackmyer C, McGarry A, Klos K, Gudesblatt M, Fafard L, Graffitti L, Schneider DP, Dhall R, Wojcieszek JM, LaFaver K, Duker A, Neefus E, Wilson-Perez H, Shprecher D, Wall P, Blindauer KA, Wheeler L, Boyd JT, Houston E, Farbman ES, Agarwal P, Eberly SW, Watts A, Tariot PN, Feigin A, Evans S, Beck C, Orme C, Edicola J, Christopher E
JAMA 2016 Jul 5;316(1):40-50. doi: 10.1001/jama.2016.8655. PMID: 27380342
Walker RH
Continuum (Minneap Minn) 2013 Oct;19(5 Movement Disorders):1242-63. doi: 10.1212/01.CON.0000436155.46909.c3. PMID: 24092289
Roos RA
Orphanet J Rare Dis 2010 Dec 20;5:40. doi: 10.1186/1750-1172-5-40. PMID: 21171977Free PMC Article

Recent systematic reviews

Tariq S, Niaz F, Waseem S, Shaikh TG, Ahmed SH, Irfan M, Nashwan AJ, Ullah I
Brain Behav 2023 Jun;13(6):e3035. Epub 2023 May 7 doi: 10.1002/brb3.3035. PMID: 37150977Free PMC Article
Bilbao A, Spanagel R
BMC Med 2022 Aug 19;20(1):259. doi: 10.1186/s12916-022-02459-1. PMID: 35982439Free PMC Article
Wu Y, Xu YY, Gao Y, Li JM, Liu XW, Wang MQ, Deng H, Xiao LL, Ren HB, Xiong BT, Pan W, Zhou XW, Wang W
Neurosurg Rev 2022 Jun;45(3):1861-1871. Epub 2022 Jan 12 doi: 10.1007/s10143-022-01735-1. PMID: 35020105
Punukollu M, Mushet N, Linney M, Hennessy C, Morton M
Dev Med Child Neurol 2016 Jan;58(1):16-28. Epub 2015 Apr 28 doi: 10.1111/dmcn.12786. PMID: 25926089
Pringsheim T, Wiltshire K, Day L, Dykeman J, Steeves T, Jette N
Mov Disord 2012 Aug;27(9):1083-91. Epub 2012 Jun 12 doi: 10.1002/mds.25075. PMID: 22692795

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