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Intention tremor

MedGen UID:
1642960
Concept ID:
C4551520
Sign or Symptom
Synonyms: Intention Tremor; Intention Tremors; Tremor, Intention
SNOMED CT: Intention tremor (30721006); Cerebellar tremor (30721006); Volitional tremor (30721006)
 
HPO: HP:0002080

Definition

A type of kinetic tremor that occurs during target directed movement is called intention tremor. That is, an oscillatory cerebellar ataxia that tends to be absent when the limbs are inactive and during the first part of voluntary movement but worsening as the movement continues and greater precision is required (e.g., in touching a target such as the patient's nose or a physician's finger). [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVIntention tremor

Conditions with this feature

Ataxia-telangiectasia syndrome
MedGen UID:
439
Concept ID:
C0004135
Disease or Syndrome
Classic ataxia-telangiectasia (A-T) is characterized by progressive cerebellar ataxia beginning between ages one and four years, oculomotor apraxia, choreoathetosis, telangiectasias of the conjunctivae, immunodeficiency, frequent infections, and an increased risk for malignancy, particularly leukemia and lymphoma. Individuals with A-T are unusually sensitive to ionizing radiation. Non-classic forms of A-T have included adult-onset A-T and A-T with early-onset dystonia.
Pelizaeus-Merzbacher disease
MedGen UID:
61440
Concept ID:
C0205711
Disease or Syndrome
PLP1 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. Heterozygous females may manifest mild-to-moderate signs of the disease.
PMM2-congenital disorder of glycosylation
MedGen UID:
138111
Concept ID:
C0349653
Disease or Syndrome
PMM2-CDG, the most common of a group of disorders of abnormal glycosylation of N-linked oligosaccharides, is divided into three clinical stages: infantile multisystem, late-infantile and childhood ataxia–intellectual disability, and adult stable disability. The clinical manifestations and course are highly variable, ranging from infants who die in the first year of life to mildly affected adults. Clinical findings tend to be similar in sibs. In the infantile multisystem presentation, infants show axial hypotonia, hyporeflexia, esotropia, and developmental delay. Feeding problems, vomiting, faltering growth, and developmental delay are frequently seen. Subcutaneous fat may be excessive over the buttocks and suprapubic region. Two distinct clinical courses are observed: (1) a nonfatal neurologic course with faltering growth, strabismus, developmental delay, cerebellar hypoplasia, and hepatopathy in infancy followed by neuropathy and retinitis pigmentosa in the first or second decade; and (2) a more severe neurologic-multivisceral course with approximately 20% mortality in the first year of life. The late-infantile and childhood ataxia–intellectual disability stage, which begins between ages three and ten years, is characterized by hypotonia, ataxia, severely delayed language and motor development, inability to walk, and IQ of 40 to 70; other findings include seizures, stroke-like episodes or transient unilateral loss of function, coagulopathy, retinitis pigmentosa, joint contractures, and skeletal deformities. In the adult stable disability stage, intellectual ability is stable; peripheral neuropathy is variable, progressive retinitis pigmentosa and myopia are seen, thoracic and spinal deformities with osteoporosis worsen, and premature aging is observed; females may lack secondary sexual development and males may exhibit decreased testicular volume. Hypogonadotropic hypogonadism and coagulopathy may occur. The risk for deep venous thrombosis is increased.
Glutathione synthetase deficiency with 5-oxoprolinuria
MedGen UID:
97988
Concept ID:
C0398746
Disease or Syndrome
Glutathione synthetase deficiency, or 5-oxoprolinuria, is an autosomal recessive disorder characterized, in its severe form, by massive urinary excretion of 5-oxoproline, metabolic acidosis, hemolytic anemia, and central nervous system damage. The metabolic defect results in decreased levels of cellular glutathione, which overstimulates the synthesis of gamma-glutamylcysteine and its subsequent conversion to 5-oxoproline (Larsson and Anderson, 2001).
Neonatal pseudo-hydrocephalic progeroid syndrome
MedGen UID:
140806
Concept ID:
C0406586
Disease or Syndrome
Wiedemann-Rautenstrauch syndrome (WDRTS) is a rare autosomal recessive neonatal progeroid disorder characterized by intrauterine growth retardation, failure to thrive, short stature, a progeroid appearance, hypotonia, and variable mental impairment (summary by Toriello, 1990). Average survival in WDRTS is 7 months, although survival into the third decade of life has been reported (Akawi et al., 2013).
Action myoclonus-renal failure syndrome
MedGen UID:
155629
Concept ID:
C0751779
Disease or Syndrome
The action myoclonus-renal failure syndrome, also known as progressive myclonic epilepsy-4 with or without renal failure (EPM4), is an autosomal recessive progressive myoclonic epilepsy associated with renal failure. Cognitive function is preserved (Badhwar et al., 2004). Some patients do not develop renal failure (Dibbens et al., 2009). For a discussion of genetic heterogeneity of progressive myoclonic epilepsy, see EPM1A (254800).
Spinocerebellar ataxia type 5
MedGen UID:
155705
Concept ID:
C0752123
Disease or Syndrome
For a general discussion of autosomal dominant spinocerebellar ataxia (SCA), see SCA1 (164400).
Spinocerebellar ataxia type 6
MedGen UID:
148458
Concept ID:
C0752124
Disease or Syndrome
Spinocerebellar ataxia type 6 (SCA6) is characterized by adult-onset, slowly progressive cerebellar ataxia, dysarthria, and nystagmus. The age of onset ranges from 19 to 73 years; mean age of onset is between 43 and 52 years. Initial symptoms are gait unsteadiness, stumbling, and imbalance (in ~90%) and dysarthria (in ~10%). Eventually all persons have gait ataxia, upper-limb incoordination, intention tremor, and dysarthria. Dysphagia and choking are common. Visual disturbances may result from diplopia, difficulty fixating on moving objects, horizontal gaze-evoked nystagmus, and vertical nystagmus. Hyperreflexia and extensor plantar responses occur in up to 40%-50%. Basal ganglia signs, including dystonia and blepharospasm, occur in up to 25%. Mentation is generally preserved.
X-linked progressive cerebellar ataxia
MedGen UID:
163229
Concept ID:
C0796205
Disease or Syndrome
SCAX1 is an X-linked recessive neurologic disorder characterized by hypotonia at birth, delayed motor development, gait ataxia, difficulty standing, dysarthria, and slow eye movements. Brain MRI shows cerebellar ataxia (summary by Bertini et al., 2000). Genetic Heterogeneity of X-linked Spinocerebellar Ataxia X-linked recessive spinocerebellar ataxia (SCAX) is a clinically and genetically heterogeneous disorder. See also SCAX2 (302600), SCAX3 (301790), SCAX4 (301840), and SCAX5 (300703).
Cayman type cerebellar ataxia
MedGen UID:
331319
Concept ID:
C1832585
Disease or Syndrome
Cayman cerebellar ataxia (ATCAY) is an autosomal recessive neurologic disorder characterized by hypotonia from birth, variable psychomotor retardation, and cerebellar dysfunction, including nystagmus, intention tremor, dysarthria, ataxic gait, and truncal ataxia. Although the disorder was initially believed to be restricted to an isolated region of Grand Cayman Island (summary by Nystuen et al., 1996; Bomar et al., 2003), one Pakistani family with the disorder and an ATCAY mutation has been reported, thus expanding the ethnic distribution (Manzoor et al., 2018).
Hypomyelinating leukodystrophy 2
MedGen UID:
325157
Concept ID:
C1837355
Disease or Syndrome
Pelizaeus-Merzbacher-like disease 1 (PMLD1) is a slowly progressive leukodystrophy that typically presents during the neonatal or early-infantile period with nystagmus, commonly associated with hypotonia, delayed acquisition of motor milestones, speech delay, and dysarthria. Over time the hypotonia typically evolves into spasticity that affects the ability to walk and communicate. Cerebellar signs (gait ataxia, dysmetria, intention tremor, head titubation, and dysdiadochokinesia) frequently manifest during childhood. Some individuals develop extrapyramidal movement abnormalities (choreoathetosis and dystonia). Hearing loss and optic atrophy are observed in rare cases. Motor impairments can lead to swallowing difficulty and orthopedic complications, including hip dislocation and scoliosis. Most individuals have normal cognitive skills or mild intellectual disability – which, however, can be difficult to evaluate in the context of profound motor impairment.
Fragile X-associated tremor/ataxia syndrome
MedGen UID:
333403
Concept ID:
C1839780
Disease or Syndrome
FMR1 disorders include fragile X syndrome (FXS), fragile X-associated tremor/ataxia syndrome (FXTAS), and fragile X-associated primary ovarian insufficiency (FXPOI). Fragile X syndrome occurs in individuals with an FMR1 full mutation or other loss-of-function variant and is nearly always characterized in affected males by developmental delay and intellectual disability along with a variety of behavioral issues. Autism spectrum disorder is present in 50%-70% of individuals with FXS. Affected males may have characteristic craniofacial features (which become more obvious with age) and medical problems including hypotonia, gastroesophageal reflux, strabismus, seizures, sleep disorders, joint laxity, pes planus, scoliosis, and recurrent otitis media. Adults may have mitral valve prolapse or aortic root dilatation. The physical and behavioral features seen in males with FXS have been reported in females heterozygous for the FMR1 full mutation, but with lower frequency and milder involvement. FXTAS occurs in individuals who have an FMR1 premutation and is characterized by late-onset, progressive cerebellar ataxia and intention tremor followed by cognitive impairment. Psychiatric disorders are common. Age of onset is typically between 60 and 65 years and is more common among males who are hemizygous for the premutation (40%) than among females who are heterozygous for the premutation (16%-20%). FXPOI, defined as hypergonadotropic hypogonadism before age 40 years, has been observed in 20% of women who carry a premutation allele compared to 1% in the general population.
Infantile-onset autosomal recessive nonprogressive cerebellar ataxia
MedGen UID:
334220
Concept ID:
C1842676
Disease or Syndrome
A rare genetic autosomal recessive cerebellar ataxia disease with characteristics of nonprogressive cerebellar ataxia, with onset in infancy, manifesting with delayed motor and speech development, gait ataxia, dysmetria, hypotonia, increased deep tendon reflexes and dysarthria. Additional variable manifestations include moderate nystagmus on lateral gaze, mild spasticity, intention tremor, short stature and pes planus. Brain imaging reveals cerebellar vermis atrophy.
Spinocerebellar ataxia type 21
MedGen UID:
375311
Concept ID:
C1843891
Disease or Syndrome
Spinocerebellar ataxia-21 (SCA21) is an autosomal dominant neurologic disorder characterized by onset in the first decades of life of slowly progressive cerebellar ataxia, which is associated with cognitive impairment in most patients (summary by Delplanque et al., 2014). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).
X-linked sideroblastic anemia with ataxia
MedGen UID:
335078
Concept ID:
C1845028
Disease or Syndrome
X-linked sideroblastic anemia and ataxia is a rare condition characterized by a blood disorder called sideroblastic anemia and movement problems known as ataxia. This condition occurs only in males.\n\nSideroblastic anemia results when developing red blood cells called erythroblasts do not make enough hemoglobin, which is the protein that carries oxygen in the blood. People with X-linked sideroblastic anemia and ataxia have mature red blood cells that are smaller than normal (microcytic) and appear pale (hypochromic) because of the shortage of hemoglobin. This disorder also leads to an abnormal accumulation of iron in red blood cells. The iron-loaded erythroblasts, which are present in bone marrow, are called ring sideroblasts. These abnormal cells give the condition its name. Unlike other forms of sideroblastic anemia, X-linked sideroblastic anemia and ataxia does not cause a potentially dangerous buildup of iron in the body. The anemia is typically mild and usually does not cause any symptoms.\n\nX-linked sideroblastic anemia and ataxia causes problems with balance and coordination that appear early in life. The ataxia primarily affects the trunk, making it difficult to sit, stand, and walk unassisted. In addition to ataxia, people with this condition often have trouble coordinating movements that involve judging distance or scale (dysmetria) and find it difficult to make rapid, alternating movements (dysdiadochokinesis). Mild speech difficulties (dysarthria), tremor, and abnormal eye movements have also been reported in some affected individuals.
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.
Spinocerebellar ataxia type 34
MedGen UID:
338703
Concept ID:
C1851481
Disease or Syndrome
Spinocerebellar ataxia-34 (SCA34) is an autosomal dominant disorder characterized by slowly progressive cerebellar ataxia. Onset usually occurs during the young adult years, and most patients remain ambulatory until late in life. One family with SCA34 also had onset of erythema and hyperkeratosis in early childhood (Cadieux-Dion et al., 2014), whereas other families have additional neurologic signs, including ocular movement disturbances and pyramidal tract signs (Ozaki et al., 2015). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).
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.
Ataxia-hypogonadism-choroidal dystrophy syndrome
MedGen UID:
347798
Concept ID:
C1859093
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).
Tremor of intention, ataxia, and lipofuscinosis
MedGen UID:
396002
Concept ID:
C1860872
Disease or Syndrome
Spinocerebellar ataxia type 29
MedGen UID:
350085
Concept ID:
C1861732
Disease or Syndrome
Spinocerebellar ataxia-29 (SCA29) is an autosomal dominant neurologic disorder characterized by onset in infancy of delayed motor development and mild cognitive delay. Affected individuals develop a very slowly progressive or nonprogressive gait and limb ataxia associated with cerebellar atrophy on brain imaging. Additional variable features include nystagmus, dysarthria, and tremor (summary by Huang et al., 2012). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).
ADan amyloidosis
MedGen UID:
396208
Concept ID:
C1861735
Disease or Syndrome
ITM2B-related cerebral amyloid angiopathy-2, also known as familial Danish dementia (FDD), is an autosomal dominant neurodegenerative disorder characterized by the progressive development of cataracts and other ocular disorders including ocular hemorrhages, hearing impairment, varying neurologic symptoms, and dementia, usually associated with paranoid reactions and temporal disturbance of consciousness. Most patients die in the fifth to sixth decade of life. Neuropathologic findings include severe widespread cerebral amyloid angiopathy, hippocampal plaques, and neurofibrillary tangles, similar to Alzheimer disease (see 104300) (summary by Vidal et al., 2000).
Gaucher disease due to saposin C deficiency
MedGen UID:
350479
Concept ID:
C1864651
Disease or Syndrome
Any Gaucher disease in which the cause of the disease is a mutation in the PSAP gene.
Hypomyelination and Congenital Cataract
MedGen UID:
501134
Concept ID:
C1864663
Congenital Abnormality
Hypomyelination and congenital cataract (HCC) is usually characterized by bilateral congenital cataracts and normal psychomotor or only mildly delayed development in the first year of life, followed by slowly progressive neurologic impairment manifest as ataxia, spasticity (brisk tendon reflexes and bilateral extensor plantar responses), and mild-to-moderate cognitive impairment. Dysarthria and truncal hypotonia are observed. Cerebellar signs (truncal titubation and intention tremor) and peripheral neuropathy (muscle weakness and wasting of the legs) are present in the majority of affected individuals. Seizures can occur. Cataracts may be absent in some individuals.
PTEN hamartoma tumor syndrome with granular cell tumor
MedGen UID:
400984
Concept ID:
C1866376
Neoplastic Process
PHARC syndrome
MedGen UID:
436373
Concept ID:
C2675204
Disease or Syndrome
Fiskerstrand type peripheral neuropathy is a slowly-progressive Refsum-like disorder associating signs of peripheral neuropathy with late-onset hearing loss, cataract and pigmentary retinopathy that become evident during the third decade of life.
EAST syndrome
MedGen UID:
411243
Concept ID:
C2748572
Disease or Syndrome
Syndrome with characteristics of seizures, sensorineural deafness, ataxia, intellectual deficit, and electrolyte imbalance. It has been described in five patients from four families. The disease is caused by homozygous or compound heterozygous mutations in the KCNJ10 gene, encoding a potassium channel expressed in the brain, spinal cord, inner ear and kidneys. Transmission is autosomal recessive.
Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 2
MedGen UID:
412914
Concept ID:
C2750234
Disease or Syndrome
Cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome (CAMRQ) is a genetically heterogeneous disorder characterized by congenital cerebellar ataxia and intellectual disability (summary by Gulsuner et al., 2011). For a discussion of genetic heterogeneity of CAMRQ, see CAMRQ1 (224050).
Hereditary spastic paraplegia 44
MedGen UID:
413042
Concept ID:
C2750784
Disease or Syndrome
A very rare, complex form of hereditary spastic paraplegia characterised by a late-onset, slowly progressive spastic paraplegia associated with mild ataxia and dysarthria, upper extremity involvement (i.e. loss of finger dexterity, dysmetria), and mild cognitive impairment, without the presence of nystagmus. A hypomyelinating leucodystrophy and thin corpus callosum is observed in all cases and psychomotor development is normal or near normal. Caused by mutations in the GJC2 gene (1q41-q42) encoding the gap junction gamma-2 protein.
Familial amyloid neuropathy
MedGen UID:
414031
Concept ID:
C2751492
Disease or Syndrome
Hereditary transthyretin (ATTR) amyloidosis is characterized by a slowly progressive peripheral sensorimotor and/or autonomic neuropathy as well as non-neuropathic changes of cardiomyopathy, nephropathy, vitreous opacities, and CNS amyloidosis. The disease usually begins in the third to fifth decade in persons from endemic foci in Portugal and Japan; onset is later in persons from other areas. Typically, sensory neuropathy starts in the lower extremities with paresthesias and hypesthesias of the feet, followed within a few years by motor neuropathy. In some persons, particularly those with early-onset disease, autonomic neuropathy is the first manifestation of the condition; findings can include: orthostatic hypotension, constipation alternating with diarrhea, attacks of nausea and vomiting, delayed gastric emptying, sexual impotence, anhidrosis, and urinary retention or incontinence. Cardiac amyloidosis is mainly characterized by progressive cardiomyopathy. Individuals with leptomeningeal amyloidosis may have the following CNS findings: dementia, psychosis, visual impairment, headache, seizures, motor paresis, ataxia, myelopathy, hydrocephalus, or intracranial hemorrhage.
Sterol carrier protein 2 deficiency
MedGen UID:
462340
Concept ID:
C3150990
Disease or Syndrome
Leukoencephalopathy-dystonia-motor neuropathy syndrome is a peroxisomal neurodegenerative disorder characterized by spasmodic torticollis, dystonic head tremor, intention tremor, nystagmus, hyposmia, and hypergonadotrophic hypogonadism with azoospermia. Slight cerebellar signs (left-sided intention tremor, balance and gait impairment) are also noted. Magnetic resonance imaging (MRI) shows bilateral hyperintense signals in the thalamus, butterfly-like lesions in the pons, and lesions in the occipital region, whereas nerve conduction studies of the lower extremities shows a predominantly motor and slight sensory neuropathy.
Autosomal recessive spinocerebellar ataxia 10
MedGen UID:
462348
Concept ID:
C3150998
Disease or Syndrome
Autosomal recessive spinocerebellar ataxia-10 is an autosomal recessive neurodegenerative disorder with onset in the teenage or young adult years of gait and limb ataxia, dysarthria, and nystagmus associated with marked cerebellar atrophy on brain imaging (summary by Vermeer et al., 2010). Some patients have low levels of coenzyme Q10 (CoQ10) in muscle and may show some clinical improvement with CoQ10 treatment (Balreira et al., 2014).
Intellectual disability, autosomal recessive 14
MedGen UID:
462812
Concept ID:
C3151462
Mental or Behavioral Dysfunction
Autosomal recessive intellectual developmental disorder-14 (MRT14) is characterized by developmental delay from birth with mild to moderate impairment of intellectual development. There are no dysmorphic features, and growth parameters and neurologic findings are normal.
Mitochondrial complex V (ATP synthase) deficiency nuclear type 2
MedGen UID:
481329
Concept ID:
C3279699
Disease or Syndrome
Mitochondrial encephalo-cardio-myopathy due to <i>TMEM70</i> mutation is characterized by early neonatal onset of hypotonia, hypetrophic cardiomyopathy and apneic spells within hours after birth accompanied by lactic acidosis, hyperammonemia and 3-methylglutaconic aciduria.
Alpha-methylacyl-CoA racemase deficiency
MedGen UID:
482058
Concept ID:
C3280428
Disease or Syndrome
AMACR deficiency is a rare autosomal recessive peroxisomal disorder characterized by adult onset of variable neurodegenerative symptoms affecting the central and peripheral nervous systems. Features may include seizures, visual failure, sensorimotor neuropathy, spasticity, migraine, and white matter hyperintensities on brain imaging. Serum pristanic acid and C27 bile acid intermediates are increased (summary by Smith et al., 2010).
Hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism
MedGen UID:
482274
Concept ID:
C3280644
Disease or Syndrome
POLR3-related leukodystrophy, a hypomyelinating leukodystrophy with specific features on brain MRI, is characterized by varying combinations of four major clinical findings: Neurologic dysfunction, typically predominated by motor dysfunction (progressive cerebellar dysfunction, and to a lesser extent extrapyramidal [i.e., dystonia], pyramidal [i.e., spasticity] and cognitive dysfunctions). Abnormal dentition (delayed dentition, hypodontia, oligodontia, and abnormally placed or shaped teeth). Endocrine abnormalities such as short stature (in ~50% of individuals) with or without growth hormone deficiency, and more commonly, hypogonadotropic hypogonadism manifesting as delayed, arrested, or absent puberty. Ocular abnormality in the form of myopia, typically progressing over several years and becoming severe. POLR3-related leukodystrophy and 4H leukodystrophy are the two recognized terms for five previously described overlapping clinical phenotypes (initially described as distinct entities before their molecular basis was known). These include: Hypomyelination, hypodontia, hypogonadotropic hypogonadism (4H syndrome); Ataxia, delayed dentition, and hypomyelination (ADDH); Tremor-ataxia with central hypomyelination (TACH); Leukodystrophy with oligodontia (LO); Hypomyelination with cerebellar atrophy and hypoplasia of the corpus callosum (HCAHC). Age of onset is typically in early childhood but later-onset cases have also been reported. An infant with Wiedemann-Rautenstrauch syndrome (neonatal progeroid syndrome) was recently reported to have pathogenic variants in POLR3A on exome sequencing. Confirmation of this as a very severe form of POLR3-related leukodystrophy awaits replication in other individuals with a clinical diagnosis of Wiedemann-Rautenstrauch syndrome.
Microcephaly-cerebellar hypoplasia-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 (Zaki et al., 2011).
Childhood encephalopathy due to thiamine pyrophosphokinase deficiency
MedGen UID:
482496
Concept ID:
C3280866
Disease or Syndrome
Thiamine metabolism dysfunction syndrome-5 (THMD5) 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 (Mayr et al., 2011). For a discussion of genetic heterogeneity of disorders due to thiamine metabolism dysfunction, see THMD1 (249270).
Peroxisome biogenesis disorder 6B
MedGen UID:
766862
Concept ID:
C3553948
Disease or Syndrome
The overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD) represent the milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy, and visual impairment. Children with the NALD presentation may reach their teens, and those with the IRD presentation may reach adulthood. Some patients with PEX10 mutations have a milder disorder characterized by childhood-onset cerebellar ataxia and neuropathy without mental retardation (summary by Waterham and Ebberink, 2012). For a complete phenotypic description and a discussion of genetic heterogeneity of PBD(NALD/IRD), see 601539. Individuals with mutations in the PEX10 gene have cells of complementation group 7 (CG7, equivalent to CGB). For information on the history of PBD complementation groups, see 214100.
Cowden syndrome 5
MedGen UID:
767432
Concept ID:
C3554518
Disease or Syndrome
PIK3CA-related overgrowth spectrum (PROS) encompasses a range of clinical findings in which the core features are congenital or early-childhood onset of segmental/focal overgrowth with or without cellular dysplasia. Prior to the identification of PIK3CA as the causative gene, PROS was separated into distinct clinical syndromes based on the tissues and/or organs involved (e.g., MCAP [megalencephaly-capillary malformation] syndrome and CLOVES [congenital lipomatous asymmetric overgrowth of the trunk, lymphatic, capillary, venous, and combined-type vascular malformations, epidermal nevi, skeletal and spinal anomalies] syndrome). The predominant areas of overgrowth include the brain, limbs (including fingers and toes), trunk (including abdomen and chest), and face, all usually in an asymmetric distribution. Generalized brain overgrowth may be accompanied by secondary overgrowth of specific brain structures resulting in ventriculomegaly, a markedly thick corpus callosum, and cerebellar tonsillar ectopia with crowding of the posterior fossa. Vascular malformations may include capillary, venous, and less frequently, arterial or mixed (capillary-lymphatic-venous or arteriovenous) malformations. Lymphatic malformations may be in various locations (internal and/or external) and can cause various clinical issues, including swelling, pain, and occasionally localized bleeding secondary to trauma. Lipomatous overgrowth may occur ipsilateral or contralateral to a vascular malformation, if present. The degree of intellectual disability appears to be mostly related to the presence and severity of seizures, cortical dysplasia (e.g., polymicrogyria), and hydrocephalus. Many children have feeding difficulties that are often multifactorial in nature. Endocrine issues affect a small number of individuals and most commonly include hypoglycemia (largely hypoinsulinemic hypoketotic hypoglycemia), hypothyroidism, and growth hormone deficiency.
Cowden syndrome 6
MedGen UID:
767433
Concept ID:
C3554519
Disease or Syndrome
The features of Cowden syndrome overlap with those of another disorder called Bannayan-Riley-Ruvalcaba syndrome. People with Bannayan-Riley-Ruvalcaba syndrome also develop hamartomas and other noncancerous tumors.  Some people with Cowden syndrome have relatives diagnosed with Bannayan-Riley-Ruvalcaba syndrome, and other affected individuals have the characteristic features of both conditions. Based on these similarities, researchers have proposed that Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome represent a spectrum of overlapping features known as PTEN hamartoma tumor syndrome (named for the genetic cause of the conditions) instead of two distinct conditions.\n\n\n\nSome people do not meet the strict criteria for a clinical diagnosis of Cowden syndrome, but they have some of the characteristic features of the condition, particularly the cancers. These individuals are often described as having Cowden-like syndrome. Both Cowden syndrome and Cowden-like syndrome are caused by mutations in the same genes.\n\nCowden syndrome is associated with an increased risk of developing several types of cancer, particularly cancers of the breast, a gland in the lower neck called the thyroid, and the lining of the uterus (the endometrium). Other cancers that have been identified in people with Cowden syndrome include kidney cancer, colorectal cancer, and an agressive form of skin cancer called melanoma. Compared with the general population, people with Cowden syndrome develop these cancers at younger ages, often beginning in their thirties or forties. People with Cowden syndrome are also more likely to develop more than one cancer during their lifetimes compared to the general population. Other diseases of the breast, thyroid, and endometrium are also common in Cowden syndrome. Additional signs and symptoms can include an enlarged head (macrocephaly) and a rare, noncancerous brain tumor called Lhermitte-Duclos disease. A small percentage of affected individuals have delayed development, intellectual disability, or autism spectrum disorder, which can affect communication and social interaction.\n\nAlmost everyone with Cowden syndrome develops hamartomas. These growths are most commonly found on the skin and mucous membranes (such as the lining of the mouth and nose), but they can also occur in the intestine and other parts of the body. The growth of hamartomas on the skin and mucous membranes typically becomes apparent by a person's late twenties.\n\nCowden syndrome is a genetic disorder characterized by multiple noncancerous, tumor-like growths called hamartomas and an increased risk of developing certain cancers.
Early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome
MedGen UID:
815995
Concept ID:
C3809665
Disease or Syndrome
Spastic paraplegia-79B (SPG79B) is an autosomal recessive progressive neurologic disorder characterized by onset of spastic paraplegia and optic atrophy in the first decade of life. Additional features are variable, but may include peripheral neuropathy, cerebellar ataxia, and cognitive impairment (summary by Rydning et al., 2017). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800).
Spinocerebellar ataxia type 35
MedGen UID:
854733
Concept ID:
C3888031
Disease or Syndrome
Spinocerebellar ataxia-35 (SCA35) is an autosomal dominant adult-onset neurologic disorder characterized by difficulty walking due to cerebellar ataxia. The age at onset ranges from teenage years to late adulthood, and the disorder is slowly progressive. Additional features may include hand tremor, dysarthria, hyperreflexia, and saccadic eye movements (summary by Guo et al., 2014). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400).
Episodic ataxia type 8
MedGen UID:
863545
Concept ID:
C4015108
Disease or Syndrome
A rare hereditary ataxia characterized by recurrent episodes of ataxia with variable frequency and duration, associated with slurred speech, generalized muscle weakness and balance disturbance. Other symptoms may occur between episodes, including intention tremor, gait ataxia, mild dysarthria, myokymia, migraine and nystagmus.
Autosomal recessive spinocerebellar ataxia 17
MedGen UID:
863738
Concept ID:
C4015301
Disease or Syndrome
Autosomal recessive spinocerebellar ataxia-17 (SCAR17) is a neurologic disorder characterized by onset of gait ataxia and cerebellar signs in early childhood. Patients also have variably impaired intellectual development (summary by Evers et al., 2016).
Hypomyelinating leukodystrophy 9
MedGen UID:
863760
Concept ID:
C4015323
Disease or Syndrome
Hypomyelinating leukodystrophy-9 is an autosomal recessive neurologic disorder characterized by onset of delayed psychomotor development, spasticity, and nystagmus in the first year of life. Additional neurologic features such as ataxia and abnormal movements may also occur. Brain imaging shows diffuse hypomyelination affecting all regions of the brain (summary by Wolf et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see 312080.
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1
MedGen UID:
897191
Concept ID:
C4225153
Disease or Syndrome
POLG-related disorders comprise a continuum of overlapping phenotypes that were clinically defined long before their molecular basis was known. Most affected individuals have some, but not all, of the features of a given phenotype; nonetheless, the following nomenclature can assist the clinician in diagnosis and management. Onset of the POLG-related disorders ranges from infancy to late adulthood. Alpers-Huttenlocher syndrome (AHS), one of the most severe phenotypes, is characterized by childhood-onset progressive and ultimately severe encephalopathy with intractable epilepsy and hepatic failure. Childhood myocerebrohepatopathy spectrum (MCHS) presents between the first few months of life and about age three years with developmental delay or dementia, lactic acidosis, and a myopathy with failure to thrive. Other findings can include liver failure, renal tubular acidosis, pancreatitis, cyclic vomiting, and hearing loss. Myoclonic epilepsy myopathy sensory ataxia (MEMSA) now describes the spectrum of disorders with epilepsy, myopathy, and ataxia without ophthalmoplegia. MEMSA now includes the disorders previously described as spinocerebellar ataxia with epilepsy (SCAE). The ataxia neuropathy spectrum (ANS) includes the phenotypes previously referred to as mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO). About 90% of persons in the ANS have ataxia and neuropathy as core features. Approximately two thirds develop seizures and almost one half develop ophthalmoplegia; clinical myopathy is rare. Autosomal recessive progressive external ophthalmoplegia (arPEO) is characterized by progressive weakness of the extraocular eye muscles resulting in ptosis and ophthalmoparesis (or paresis of the extraocular muscles) without associated systemic involvement; however, caution is advised because many individuals with apparently isolated arPEO at the onset develop other manifestations of POLG-related disorders over years or decades. Of note, in the ANS spectrum the neuropathy commonly precedes the onset of PEO by years to decades. Autosomal dominant progressive external ophthalmoplegia (adPEO) typically includes a generalized myopathy and often variable degrees of sensorineural hearing loss, axonal neuropathy, ataxia, depression, parkinsonism, hypogonadism, and cataracts (in what has been called "chronic progressive external ophthalmoplegia plus," or "CPEO+").
Tremor, hereditary essential, 5
MedGen UID:
897748
Concept ID:
C4225223
Disease or Syndrome
Hereditary essential tremor-5 is an autosomal dominant neurologic disorder characterized by kinetic, intention, and/or postural tremor mainly affecting the upper limbs. The age at onset and severity are highly variable, even within families (summary by Hor et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of hereditary essential tremor, see ETM1 (190300).
Neuropathy, hereditary motor and sensory, type 6B
MedGen UID:
895482
Concept ID:
C4225302
Disease or Syndrome
Hereditary motor and sensory neuropathy type VIB is an autosomal recessive complex progressive neurologic disorder characterized mainly by early-onset optic atrophy resulting in progressive visual loss and peripheral axonal sensorimotor neuropathy with highly variable age at onset and severity. Affected individuals may also have cerebellar or pontocerebellar atrophy on brain imaging, and they may show abnormal movements such as ataxia, dysmetria, and myoclonus (summary by Abrams et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of HMSN6, see HMSN6A (601152).
Spinocerebellar ataxia, autosomal recessive 22
MedGen UID:
934748
Concept ID:
C4310781
Disease or Syndrome
Any autosomal recessive cerebellar ataxia in which the cause of the disease is a mutation in the VWA3B gene.
Spinocerebellar ataxia type 40
MedGen UID:
1385103
Concept ID:
C4518336
Disease or Syndrome
A very rare disease with characteristics of adult-onset unsteady gait and dysarthria, followed by wide-based gait, gait ataxia, ocular dysmetria, intention tremor, scanning speech, hyperreflexia and dysdiadochokinesis.
Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1
MedGen UID:
1639436
Concept ID:
C4551552
Disease or Syndrome
VLDLR cerebellar hypoplasia (VLDLR-CH) is characterized by non-progressive congenital ataxia that is predominantly truncal and results in delayed ambulation, moderate-to-profound intellectual disability, dysarthria, strabismus, and seizures. Children either learn to walk very late (often after age 6 years) or never achieve independent ambulation. Brain MRI findings include hypoplasia of the inferior portion of the cerebellar vermis and hemispheres, simplified gyration of the cerebral hemispheres, and small brain stem – particularly the pons.
Perrault syndrome 1
MedGen UID:
1640257
Concept ID:
C4551721
Disease or Syndrome
Perrault syndrome is characterized by sensorineural hearing loss (SNHL) in males and females and ovarian dysfunction in females. SNHL is bilateral and ranges from profound with prelingual (congenital) onset to moderate with early-childhood onset. When onset is in early childhood, hearing loss can be progressive. Ovarian dysfunction ranges from gonadal dysgenesis (absent or streak gonads) manifesting as primary amenorrhea to primary ovarian insufficiency (POI) defined as cessation of menses before age 40 years. Fertility in affected males is reported as normal (although the number of reported males is limited). Neurologic features described in some individuals with Perrault syndrome include learning difficulties and developmental delay, cerebellar ataxia, and motor and sensory peripheral neuropathy.
Leukodystrophy, hypomyelinating, 15
MedGen UID:
1633653
Concept ID:
C4693733
Disease or Syndrome
Hypomyelinating leukodystrophy-15 is an autosomal recessive neurodegenerative disorder characterized by onset of motor and cognitive impairment in the first or second decade of life. Features include dystonia, ataxia, spasticity, and dysphagia. Most patients develop severe optic atrophy, and some have hearing loss. Brain imaging shows hypomyelinating leukodystrophy with thin corpus callosum. The severity of the disorder is variable (summary by Mendes et al., 2018) For a discussion of genetic heterogeneity of HLD, see 312080.
Leukodystrophy, hypomyelinating, 16
MedGen UID:
1631337
Concept ID:
C4693779
Disease or Syndrome
Hypomyelinating leukodystrophy-16 is an autosomal dominant neurologic disorder characterized by onset of hypotonia, nystagmus, and mildly delayed motor development in infancy. Affected individuals have motor disabilities, including ataxic or broad-based gait, hyperreflexia, intention tremor, dysmetria, and a mild pyramidal syndrome. Some patients have cognitive impairment, whereas others may have normal cognition or mild intellectual disability with speech difficulties. Brain imaging typically shows hypomyelination, leukodystrophy, and thin corpus callosum (summary by Simons et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of hypomyelinating leukodystrophy, see 312080.
Ververi-Brady syndrome
MedGen UID:
1647785
Concept ID:
C4693824
Disease or Syndrome
Ververi-Brady syndrome (VEBRAS) is characterized by mild developmental delay, mildly impaired intellectual development and speech delay, and mild dysmorphic facial features. Affected individuals can usually attend mainstream schools with support, and may also show autistic features (summary by Ververi et al., 2018).
Autosomal recessive spinocerebellar ataxia 14
MedGen UID:
1636182
Concept ID:
C4706415
Disease or Syndrome
Autosomal recessive spinocerebellar ataxia-14 (SCAR14) is a neurologic disorder characterized by delayed psychomotor development, severe early-onset gait ataxia, eye movement abnormalities, cerebellar atrophy on brain imaging, and impaired intellectual development (summary by Lise et al., 2012).
Neurodevelopmental disorder with spasticity and poor growth
MedGen UID:
1648309
Concept ID:
C4748081
Disease or Syndrome
Neurodevelopmental disorder with spasticity and poor growth (NEDSG) is an autosomal recessive disorder characterized by severe early-onset encephalopathy with progressive microcephaly (Nahorski et al., 2018).
Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures
MedGen UID:
1648391
Concept ID:
C4748527
Disease or Syndrome
Stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS) is an autosomal recessive neurodegenerative disorder with onset in the first years of life following normal early development. Patient have cyclic episodic deterioration in response to stress, such as infection or febrile illness. The severity is highly variable: some patients develop seizures early in life that are associated with loss of developmental milestones and early sudden death in childhood, whereas others present at a later age with muscle weakness, gait ataxia, impaired speech, more subtle clinical deterioration, and cognitive decline. Neurologic involvement includes gait ataxia, cerebellar signs associated with cerebellar atrophy, generalized brain atrophy, impaired intellectual development, hearing loss, and peripheral neuropathy (summary by Ghosh et al., 2018).
Neurodevelopmental disorder with central and peripheral motor dysfunction
MedGen UID:
1674767
Concept ID:
C5193049
Disease or Syndrome
Neurodevelopmental disorder with central and peripheral motor dysfunction (NEDCPMD) is an autosomal recessive neurologic disorder with a highly variable phenotype. At the severe end of the spectrum, patients may have hypotonia apparent from birth, necessitating mechanical respiration and tube-feeding, and global developmental delay with absence of reaction to touch and no eye contact. At the mild end of the spectrum, patients may present with infantile-onset progressive ataxia and demyelinating peripheral neuropathy. The disorder is caused by mutation in the NFASC gene, which has several neuronal- and glial-specific transcripts. The variable clinical phenotype may be caused by several factors, including the severity of the mutation, the selective involvement of distinct isoforms by pathogenic variants, and the presence of genetic modifiers (summary by Monfrini et al., 2019).
Facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome
MedGen UID:
1679105
Concept ID:
C5193066
Disease or Syndrome
A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by variable intellectual disability and/or developmental delay, epilepsy, generalized hypertrichosis, severe gingival overgrowth and visual impairment in some patients. Common craniofacial features include bitemporal narrowing, bushy and straight eyebrows, long eyelashes, low-set ears, deep/short philtrum, everted upper lip, prominent upper and lower vermilion, wide mouth, micrognathia, and retrognathia.
Leukodystrophy, hypomyelinating, 19, transient infantile
MedGen UID:
1684698
Concept ID:
C5231463
Disease or Syndrome
Transient infantile hypomyelinating leukodystrophy-19 (HLD19) is a disorder characterized by onset of transient neurologic abnormalities in early infancy, with resolution within the first or second decades. Affected individuals typically present in the newborn period or in early infancy with nystagmus and motor deficits associated with marked hypomyelination on brain imaging. Both neurologic impairment and abnormal brain imaging spontaneously resolve during childhood. Most patients have normal cognition and can attend regular schools, although some may have persistent neurologic deficits, such as gait ataxia, speech pronunciation defects, and/or mild cognitive impairment (summary by Yan et al., 2019). For a discussion of genetic heterogeneity of HLD, see 312080.
Epilepsy, progressive myoclonic, 11
MedGen UID:
1716712
Concept ID:
C5394362
Disease or Syndrome
Progressive myoclonic epilepsy-11 (EPM11) is a neurodegenerative disorder characterized by onset of developmental regression and various types of seizures around 2 years of age after relatively normal early development. The seizures are usually refractory to treatment and are associated with multiple abnormalities on EEG. During the first and second decades, affected individuals develop additional neurologic signs and symptoms, including pyramidal, extrapyramidal, and cerebellar signs such as spasticity, loss of independent ambulation, myoclonus, tremor, and ataxia. Cognitive impairment is severe, and patients can speak only a few words or are non-verbal (summary by Hamanaka et al., 2020). For discussion of genetic heterogeneity of progressive myoclonic epilepsy, see EPM1A (254800).
Marbach-Rustad progeroid syndrome
MedGen UID:
1784907
Concept ID:
C5543388
Disease or Syndrome
Marbach-Rustad progeroid syndrome (MARUPS) is characterized by progeroid appearance with little subcutaneous fat and triangular facies, growth retardation with short stature, hypoplastic mandible crowded with unerupted supernumerary teeth, and cerebellar intention tremor. Psychomotor development is normal. Although features are reminiscent of Hutchinson-Gilford progeria syndrome (HGPS; 176670), MARUPS is less severe, with a relatively good prognosis. Two patients have been reported (Marbach et al., 2019).
Ataxia, intention tremor, and hypotonia syndrome, childhood-onset
MedGen UID:
1787902
Concept ID:
C5543478
Disease or Syndrome
Childhood-onset ataxia, intention tremor, and hypotonia syndrome (ATITHS) is a neurodevelopmental disorder characterized by delayed walking due to ataxia, intention tremor, and hypotonia apparent from early childhood. Affected individuals have global developmental delay with mildly impaired intellectual development and speech delay or learning disabilities. Eye movement abnormalities may also be present. Brain imaging shows cerebellar atrophy in some patients (summary by Webb et al., 2021).
Developmental delay, impaired speech, and behavioral abnormalities
MedGen UID:
1794167
Concept ID:
C5561957
Disease or Syndrome
Developmental delay, impaired speech, and behavioral abnormalities (DDISBA) is characterized by global developmental delay apparent from early childhood. Intellectual disability can range from mild to severe. Additional variable features may include dysmorphic facial features, seizures, hypotonia, motor abnormalities such as Tourette syndrome or dystonia, and hearing loss (summary by Cousin et al., 2021).
Intellectual developmental disorder, autosomal dominant 69
MedGen UID:
1808299
Concept ID:
C5676896
Mental or Behavioral Dysfunction
Autosomal dominant intellectual developmental disorder-69 (MRD69) is characterized by developmental delay with variably impaired intellectual development. Additional features may include intention tremor in infancy and seizures in childhood, with remission of these in adolescence (Alkhater et al., 2019).
Gastrointestinal defects and immunodeficiency syndrome 2
MedGen UID:
1811526
Concept ID:
C5676901
Disease or Syndrome
PI4KA-related disorder is a clinically variable disorder characterized primarily by neurologic dysfunction (limb spasticity, developmental delay, intellectual disability, seizures, ataxia, nystagmus), gastrointestinal manifestations (multiple intestinal atresia, inflammatory bowel disease), and combined immunodeficiency (leukopenia, variable immunoglobulin defects). Age of onset is typically antenatal or in early childhood; individuals can present with any combination of these features. Rare individuals present with later-onset hereditary spastic paraplegia. Brain MRI findings can include hypomyelinating leukodystrophy, cerebellar hypoplasia/atrophy, thin or dysplastic corpus callosum, and/or perisylvian polymicrogyria.
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.
Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development 1
MedGen UID:
1808104
Concept ID:
C5677021
Disease or Syndrome
Craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome-1 (CFSMR1) is characterized by cranial involvement with macrocrania at birth, brachycephaly, anomalies of middle fossa structures including hypoplasia of corpus callosum, enlargement of septum pellucidum, and dilated lateral ventricles, as well as cortical atrophy and hypodensity of the gray matter. Facial dysmorphisms include flat face, hypertelorism, epicanthal folds, synophrys, broad nasal bridge, cleft lip and cleft palate, and low-set posteriorly rotated ears. Patients also exhibit short neck and multiple costal and vertebral anomalies. The face is rather characteristic, and various authors have consistently reported affable/friendly personality, despite intellectual delay (summary by Alanay et al., 2014). Genetic Heterogeneity of Craniofacial Dysmorphism, Skeletal Anomalies, and Impaired Intellectual Development Syndrome CFSMR2 (616994) is caused by mutation in the RAB5IF gene (619960) on chromosome 20q11.
Neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies
MedGen UID:
1823969
Concept ID:
C5774196
Disease or Syndrome
Neurodevelopmental disorder with intention tremor, pyramidal signs, dyspraxia, and ocular anomalies (NEDITPO) is an autosomal recessive multiple congenital anomaly syndrome characterized by mild to moderate intellectual disability, dysmorphic facial features, intention tremor, dyspraxia, and vertical strabismus (Rahikkala et al., 2022).
Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures
MedGen UID:
1823986
Concept ID:
C5774213
Disease or Syndrome
Neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures (NEDHLSS) is characterized by global developmental delay apparent from infancy. Affected individuals show severe hypotonia with delayed walking or inability to walk, poor or absent speech, and impaired intellectual development with behavioral abnormalities. Most patients have early-onset seizures, mild skeletal defects that are usually distal, and nonspecific dysmorphic features. More severely affected individuals have additional congenital abnormalities; however, cardiac involvement is rare (summary by Rodan et al., 2021).
Spinocerebellar ataxia, autosomal recessive 33
MedGen UID:
1824070
Concept ID:
C5774297
Disease or Syndrome
Autosomal recessive spinocerebellar ataxia-33 (SCAR33) is a neurologic disorder characterized by delayed motor development apparent in infancy, unsteady ataxic gait, intention tremor, nystagmus, and speech delay with dysarthria. Some patients have seizures and/or learning difficulties. Brain imaging shows cerebellar hypoplasia (Elsaid et al., 2017).
Spastic paraplegia 79A, autosomal dominant, with ataxia
MedGen UID:
1824073
Concept ID:
C5774300
Disease or Syndrome
Autosomal dominant spastic paraplegia-79A with ataxia (SPG79A) is a slowly progressive neurodegenerative disorder characterized predominantly by cerebellar and/or sensory ataxia and spasticity of the lower limbs leading to gait difficulties. The onset is usually in adulthood (median age of 49 years), but can range from childhood to age 70. Additional common features include sensorimotor neuropathy and visual impairment with optic atrophy. The disorder is slowly progressive (Park et al., 2022).
Intellectual developmental disorder, autosomal recessive 79
MedGen UID:
1841189
Concept ID:
C5830553
Disease or Syndrome
Autosomal recessive intellectual developmental disorder-79 (MRT79) is characterized by global developmental delay apparent from infancy. Affected individuals have mildly delayed walking with an ataxic gait and severely impaired intellectual development with poor or absent speech. Additional features may include postnatal microcephaly and dysmorphic features (Van Bergen et al., 2022).
Dystonia 22, juvenile-onset
MedGen UID:
1841281
Concept ID:
C5830645
Disease or Syndrome
Juvenile-onset dystonia-22 (DYT22JO) is an autosomal recessive disorder characterized by progressive, generalized dystonia associated with cognitive decline and cerebellar atrophy on brain imaging (Mencacci et al., 2021).

Professional guidelines

PubMed

Louis ED
Continuum (Minneap Minn) 2016 Aug;22(4 Movement Disorders):1143-58. doi: 10.1212/CON.0000000000000346. PMID: 27495202
Bötzel K, Tronnier V, Gasser T
Dtsch Arztebl Int 2014 Mar 28;111(13):225-35; quiz 236. doi: 10.3238/arztebl.2014.0225. PMID: 24739887Free PMC Article
Deuschl G
J Neural Transm Suppl 1999;56:211-20. doi: 10.1007/978-3-7091-6360-3_14. PMID: 10370914

Recent clinical studies

Etiology

Raju SS, Niranjan A, Monaco EA, Flickinger JC, Lunsford LD
J Neurosurg 2018 Apr;128(4):1214-1221. Epub 2017 Jun 30 doi: 10.3171/2017.1.JNS162512. PMID: 28665251
Fujioka S, Algom AA, Murray ME, Sanchez-Contreras MY, Tacik P, Tsuboi Y, Van Gerpen JA, Uitti RJ, Rademakers R, Ross OA, Wszolek ZK, Dickson DW
Parkinsonism Relat Disord 2016 Jun;27:93-7. Epub 2016 Mar 22 doi: 10.1016/j.parkreldis.2016.03.015. PMID: 27039056Free PMC Article
Genton P, Velizarova R, Dravet C
Epilepsia 2011 Apr;52 Suppl 2:44-9. doi: 10.1111/j.1528-1167.2011.03001.x. PMID: 21463279
Louis ED, Lynch T, Ford B, Greene P, Bressman SB, Fahn S
Arch Neurol 1996 May;53(5):450-4. doi: 10.1001/archneur.1996.00550050080027. PMID: 8624221
Goldman MS, Kelly PJ
J Neurosurg 1992 Aug;77(2):223-9. doi: 10.3171/jns.1992.77.2.0223. PMID: 1625009

Diagnosis

Cabal-Herrera AM, Tassanakijpanich N, Salcedo-Arellano MJ, Hagerman RJ
Int J Mol Sci 2020 Jun 20;21(12) doi: 10.3390/ijms21124391. PMID: 32575683Free PMC Article
Louis ED
Continuum (Minneap Minn) 2019 Aug;25(4):959-975. doi: 10.1212/CON.0000000000000748. PMID: 31356289
Pérez-Riera AR, Barbosa-Barros R, Daminello-Raimundo R, de Abreu LC
Ann Noninvasive Electrocardiol 2018 Mar;23(2):e12494. Epub 2017 Sep 20 doi: 10.1111/anec.12494. PMID: 28940924Free PMC Article
Louis ED
Continuum (Minneap Minn) 2016 Aug;22(4 Movement Disorders):1143-58. doi: 10.1212/CON.0000000000000346. PMID: 27495202
Bötzel K, Tronnier V, Gasser T
Dtsch Arztebl Int 2014 Mar 28;111(13):225-35; quiz 236. doi: 10.3238/arztebl.2014.0225. PMID: 24739887Free PMC Article

Therapy

Louis ED
Continuum (Minneap Minn) 2019 Aug;25(4):959-975. doi: 10.1212/CON.0000000000000748. PMID: 31356289
Pérez-Riera AR, Barbosa-Barros R, Daminello-Raimundo R, de Abreu LC
Ann Noninvasive Electrocardiol 2018 Mar;23(2):e12494. Epub 2017 Sep 20 doi: 10.1111/anec.12494. PMID: 28940924Free PMC Article
Raju SS, Niranjan A, Monaco EA, Flickinger JC, Lunsford LD
J Neurosurg 2018 Apr;128(4):1214-1221. Epub 2017 Jun 30 doi: 10.3171/2017.1.JNS162512. PMID: 28665251
Fujioka S, Algom AA, Murray ME, Sanchez-Contreras MY, Tacik P, Tsuboi Y, Van Gerpen JA, Uitti RJ, Rademakers R, Ross OA, Wszolek ZK, Dickson DW
Parkinsonism Relat Disord 2016 Jun;27:93-7. Epub 2016 Mar 22 doi: 10.1016/j.parkreldis.2016.03.015. PMID: 27039056Free PMC Article
Deuschl G, Wenzelburger R, Löffler K, Raethjen J, Stolze H
Brain 2000 Aug;123 ( Pt 8):1568-80. doi: 10.1093/brain/123.8.1568. PMID: 10908187

Prognosis

Louis ED, Faust PL
Cerebellum 2020 Dec;19(6):879-896. doi: 10.1007/s12311-020-01160-4. PMID: 32666285Free PMC Article
Raju SS, Niranjan A, Monaco EA, Flickinger JC, Lunsford LD
J Neurosurg 2018 Apr;128(4):1214-1221. Epub 2017 Jun 30 doi: 10.3171/2017.1.JNS162512. PMID: 28665251
Bötzel K, Tronnier V, Gasser T
Dtsch Arztebl Int 2014 Mar 28;111(13):225-35; quiz 236. doi: 10.3238/arztebl.2014.0225. PMID: 24739887Free PMC Article
Genton P, Velizarova R, Dravet C
Epilepsia 2011 Apr;52 Suppl 2:44-9. doi: 10.1111/j.1528-1167.2011.03001.x. PMID: 21463279
Louis ED, Lynch T, Ford B, Greene P, Bressman SB, Fahn S
Arch Neurol 1996 May;53(5):450-4. doi: 10.1001/archneur.1996.00550050080027. PMID: 8624221

Clinical prediction guides

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