NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.

Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021.

Cover of GeneReviews®

GeneReviews® [Internet].

Show details

Hereditary Ataxia Overview

, MD.

Author Information

Initial Posting: ; Last Revision: July 25, 2019.

Estimated reading time: 45 minutes


Clinical characteristics.

The hereditary ataxias are a group of genetic disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. In this GeneReview the hereditary ataxias are categorized by mode of inheritance and gene (or chromosome locus) in which pathogenic variants occur.


Inherited (genetic) forms of ataxia must be distinguished from the many acquired (non-genetic) causes of ataxia. The genetic forms of ataxia are diagnosed by family history, physical examination, neuroimaging, and molecular genetic testing.

Genetic counseling.

The hereditary ataxias can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Genetic counseling and risk assessment depend on determination of the specific cause of an inherited ataxia in an individual.


Treatment of manifestations: Canes, walkers, and wheelchairs for gait ataxia; use of special devices to assist with handwriting, buttoning, and use of eating utensils; speech therapy and/or computer-based devices for those with dysarthria and severe speech deficits.

Prevention of primary manifestations: With the exception of vitamin E therapy for ataxia with vitamin E deficiency (AVED), no specific treatments exist for hereditary ataxia.


Clinical Manifestations of Hereditary Ataxia

Clinical manifestations of hereditary ataxia are poor coordination of movement and a wide-based, uncoordinated, unsteady gait. Poor coordination of the limbs and of speech (dysarthria) are often present.

Hereditary ataxia may result from one or any combination of the following:

  • Dysfunction of the cerebellum and its associated systems
  • Lesions in the spinal cord
  • Peripheral sensory loss

Establishing the Diagnosis of Hereditary Ataxia

Establishing the diagnosis of hereditary ataxia requires the following:

  • Detection on neurologic examination of typical clinical symptoms and signs including poorly coordinated gait and finger/hand movements, often associated with dysarthria and nystagmus
  • Documenting the hereditary nature by the presence of:
    • A positive family history of ataxia;
    • A causative (i.e., pathogenic) allelic variant or variants one of the many genes associated with hereditary ataxia;
    • A clinical phenotype characteristic of a genetic form of ataxia.
      Note: In some individuals with no family history of ataxia it may not be possible to establish a genetic cause if results of all available genetic tests are normal.

Differential Diagnosis of Hereditary Ataxia

Differential diagnosis of hereditary ataxia includes acquired, non-genetic causes of ataxia, such as alcoholism, vitamin deficiencies, multiple sclerosis, vascular disease, primary or metastatic tumors, or paraneoplastic diseases associated with occult carcinoma of the ovary, breast, or lung.

The possibility of an acquired cause of ataxia needs to be considered in each individual with ataxia because a specific treatment may be available [Shakkottai & Fogel 2013].

Prevalence of Hereditary Ataxia

Prevalence of the autosomal dominant cerebellar ataxias (ADCAs) is estimated to be approximately 1-5:100,000 population [van de Warrenburg et al 2002, Ruano et al 2014].

Of the autosomal dominant ataxias, SCA3 is the most common worldwide, followed by SCA1, 2, 6, and 7 (see Figure 1).

Figure 1. . Worldwide distribution of SCA subtypes [Schöls et al 1997, Moseley et al 1998, Saleem et al 2000, Storey et al 2000, Tang et al 2000, Maruyama et al 2002, Silveira et al 2002, van de Warrenburg et al 2002, Dryer et al 2003, Brusco et al 2004, Schöls et al 2004, Shimizu et al 2004, Zortea et al 2004, Jiang et al 2005, Jiang et al 2013].

Figure 1.

Worldwide distribution of SCA subtypes [Schöls et al 1997, Moseley et al 1998, Saleem et al 2000, Storey et al 2000, Tang et al 2000, Maruyama et al 2002, Silveira et al 2002, van de Warrenburg et al 2002, Dryer et al 2003, Brusco et al 2004, (more...)

Autosomal recessive types of hereditary ataxia account for approximately 3:100,000 [Ruano et al 2014] with Friedreich ataxia, ataxia-telangiectasia, and ataxia oculomotor apraxia being most common (see AOA1, AOA2).

The prevalance of genetic childhood ataxia varies from 0.1 to 10 cases per 100,000 population [Musselman et al 2014].


The hereditary ataxias can be subdivided first by mode of inheritance (i.e., autosomal dominant, autosomal recessive, X-linked, and mitochondrial) and secondarily by the gene in which pathogenic variants occur or chromosome locus to which the phenotype has been mapped.

The nomenclature for the hereditary ataxias is a work in progress because of the large number of subtypes and their extensive phenotypic overlap.

  • Spinocerebellar ataxia (SCA) is a historical term first used in the 1950s based on Friedreich ataxia as a model. SCA now refers to autosomal dominant hereditary ataxia, and the numbers are assigned in the order in which the disease was identified (initially by linkage analysis and more recently by gene discovery). In some SCAs ataxia is the only phenotypic finding (e.g., SCA6), whereas other SCAs may have a complicated phenotype (e.g., SCA3). Some SCAs have spinal cord involvement, but many do not. Some of the complicated forms have not been given an SCA number (e.g., DRPLA).
  • SCAR refers to autosomal recessive spinocerebellar ataxias.
  • EA refers to episodic ataxias.
  • SPAX refers to ataxias that often have a prominent component of spasticity.

The hereditary ataxias have also been summarized by Finsterer [2009a], Paulson [2009], Dürr [2010], Jayadev & Bird [2013], Sandford & Burmeister [2014], and Sun et al [2016]. The phenotypic overlap within the hereditary ataxias is also reflected in the extensive range of neuropathologic features detailed by Seidel et al [2012] and Rüb et al [2013].

Autosomal Dominant Cerebellar Ataxias (ADCA)

Synonyms for ADCA used prior to the identification of the molecular genetic basis of these disorders were Marie's ataxia, inherited olivopontocerebellar atrophy, cerebello-olivary atrophy, or the more generic term, spinocerebellar degeneration.

The autosomal dominant cerebellar ataxias for which specific genetic information is available are summarized in Table 1. Most are spinocerebellar ataxias (SCA); one is a complex form (DRPLA). See Table 2 for the episodic ataxias, all of which are inherited in an autosomal dominant manner, and Table 5 for the spastic ataxias, all but one of which are inherited in an autosomal recessive manner.

No specific treatments can prevent, delay, or reverse the major clinical features of the dominant SCAs. Some manifestations such as seizures can be treated; certain rehabilitative measures can be of benefit.

Often, one autosomal dominant ataxia cannot be differentiated from another because: (1) the most frequent manifestations of all of AD ataxias are progressive adult-onset gait ataxia (often with hand dysmetria) and dysarthria associated with cerebellar atrophy on brain imaging; (2) the ages of onset often overlap.

Table 1.

Autosomal Dominant Cerebellar Ataxias: Molecular Genetics & Clinical Features

DiseaseGene / Locus 1Distinguishing Clinical Features 2OtherReferences 3 / Selected OMIM Links
  • Pyramidal signs
  • Peripheral neuropathy
Occasional cognitive decline 164400
  • Slow saccadic eye movements
  • Peripheral neuropathy
  • ↓ DTRs
  • Dementia
Large Cuban founder population 183090
  • Pyramidal & extrapyramidal signs
  • Lid retraction, nystagmus, & ↓ saccade velocity
  • Amyotrophy fasciculations, sensory loss
Large Portugese founder population; known as Machado-Joseph disease; shortens life span 109150
SCA4 416q22.1
  • Sensory axonal neuropathy
  • Deafness
Flanigan et al [1996], Hellenbroich et al [2003], Edener et al [2011]
/ 600223
  • Early onset
  • Slow course
Sometimes called Lincoln ataxia; normal life spanRanum et al [1994], Stevanin et al [1999], Bürk et al [2004], Ikeda et al [2006]
/ 600224
  • Sometimes episodic ataxia
  • Very slow progression
Often adult onset; normal life span 183086
  • Visual loss w/retinopathy
Often rapidly progressive; shortens life span 164500
  • Slowly progressive
  • Sometimes brisk DTRs, ↓ vibration sense
  • Rarely, cognitive impairment
SCA9Not assigned
  • Occasional seizures
Large Mexican founder population 603516
  • Mild
  • Remain ambulatory
  • Slowly progressive ataxia
  • Action tremor in the 30s
  • Hyperreflexia
  • Subtle parkinsonism possible
  • Cognitive/psychiatric disorders incl dementia
  • Mild ID
  • Short stature
  • Early axial myoclonus
  • Pure ataxia
  • Very slow progression
  • Head tremor
Miyoshi et al [2001], Miura et al [2006]
  • Mental deterioration
  • Occasional chorea, dystonia, myoclonus, epilepsy
  • Ataxia w/early sensory/motor neuropathy
  • Nystagmus
  • Dysarthria
  • ↓ tendon reflexes
Brkanac et al [2002], Brkanac et al [2009]
/ 607458
SCA19/22 KCND3
  • Slowly progressive
  • Rare cognitive impairment
  • Myoclonus
  • Hyperreflexia
Schelhaas et al [2001], Verbeek et al [2002], Chung et al [2003], Chung & Soong [2004], Schelhaas et al [2004], Duarri et al [2012], Lee et al [2012]
/ 607346
SCA20 11q12
  • Early dysarthria
  • Spasmodic dysphonia
  • Hyperreflexia
  • Bradykinesia
  • Mild-to-severe early-onset cognitive impairment
Devos et al [2001], Vuillaume et al [2002], Delplanque et al [2014]
/ 607454
  • Dysarthria
  • Abnormal eye movements
  • ↓ vibration & position sense
Verbeek et al [2004], Bakalkin et al [2010]
/ 610245
  • Sensory neuropathy
Stevanin et al [2003]
/ 608703
  • Dysarthria
  • Irregular visual pursuits
Yu et al [2005], Hekman et al [2012]
/ 609306
  • Early-onset tremor
  • Dyskinesia
  • Cognitive deficits
van Swieten et al [2003], Brusse et al [2006]
/ 609307
SCA28 6 AFG3L2
  • Nystagmus
  • Ophthalmoparesis
  • Ptosis
  • ↑ tendon reflexes
Svenstrup et al [2017]
/ 610246
  • Learning deficits
Dudding et al [2004],
Shadrina et al [2016]
/ 117360
  • Hyperreflexia
Storey et al [2009]
/ 613371
  • Normal sensation
Common in JapanNagaoka et al [2000], Sato et al [2009], Sakai et al [2010], Edener et al [2011]
/ 117210
  • Skin changes disappear in adulthood
Cadieux-Dion et al [2014]
/ 133190
  • Hyperreflexia
  • Babinski responses
Wang et al [2010]
/ 613908
  • Muscle fasiculations
  • Tongue atrophy
  • Hyperreflexia
SCA37 1p32
  • Abnormal vertical eye movements
Serrano-Munuera et al [2013]
  • Adult onset
  • Axonal neuropathy
Di Gregorio et al [2014]
  • Adult onset
  • Brisk reflexes
  • Spasticity
Tsoi et al [2014]
/ 616053
  • Adult onset
  • Uncomplicated ataxia
  • Mild pyramidal signs
  • Saccadic pursuit
p.Arg175His founder variantCoutelier et al [2015a]
/ 616795
  • Sensorimotor axonal neuropathy
  • Spasticity
  • Adult onset
  • Adult onset
  • Sensory neuropathy
  • Mild cerebellar atrophy
  • DD
  • ID
  • Seizures
  • Progressive cognitive disability may precede ataxia.
  • Chorea
  • Seizures
  • Dementia
  • Myoclonus
Mimics Huntington disease; more common in Japan 125370
  • Deafness
  • Sensory loss
  • Narcolepsy
Klein et al [2011], Klein et al [2013]
Hypomyelinating leukoencephalopathy TUBB4A
  • Hypomyelination
  • Basal ganglia atrophy
  • Rigidity
  • Dystonia
  • Chorea
Hamilton et al [2014], Miyatake et al [2014]
/ 612438
GRID2-related spinocerebellar ataxia GRID2
  • Cognitive delay
  • Abnormal eye movements
  • Hearing loss
Rarely AD; primarily assoc w/AR inheritance 7 Coutelier et al [2015b]
Pure cerebellar ataxiaC9orf72 8Other family members may have frontotemporal dementia or motor neuron disease. 9 Corcia et al [2016]
Cerebellar atrophy with epileptic encephalopathy FGF12
  • Infantile seizures
  • Intellectual deficits
  • Microcephaly
Siekierska et al [2016]
Rapid-onset ataxia ATP1A3
  • Cerebellar atrophy
See footnote 10 for allelic disorders. Sweadner et al [2016]

See Spinocerebellar ataxia: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM.

DD = developmental delay; DTRs = deep tendon reflexes; ID = intellectual disability


Chromosome locus is given only when the gene is unknown.


All have gait ataxia.


References included when there is no GeneReview


SCA31 is caused by a complex pentanucleotide (TGGAA) n repeat insertion in the introns of TK2 and BEAN appeared crucial for SCA31 pathogenesis [Sato et al 2009]. SCA31 is not allelic to SCA4 which is in the same region (16q22.1) [Edener et al 2011].


SCA 6 is allelic to EA2 (see Table 2) and familial hemiplegic migraine type 1.


Allelic to SPAX5


See Table 3.


A C9orf72 hexarepeat expansion was associated with single case of pure cerebellar ataxia [Corcia et al 2016].


Expansion of the C9orf72 hexarepeat is usually associated with amyotrophic lateral sclerosis or frontotemporal dementia.


The spectrum of ATP1A3-related neurologic disorders also includes rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome.

The prevalence of individual subtypes of ADCA may vary from region to region, frequently because of founder effects. For example,

Nucleotide-repeat disorders. Anticipation can be observed in the autosomal dominant ataxias in which CAG trinucleotide repeats occur (Table 1). Anticipation refers to earlier onset and increasing severity of disease in subsequent generations of a family. In the trinucleotide-repeat diseases, anticipation results from expansion in the number of CAG repeats that occurs with transmission of the gene to subsequent generations. ATN1 (DRPLA) and ATXN7 (SCA7) have particularly unstable CAG repeats [La Spada 1997, Nance 1997]. In SCA7, anticipation may be so extreme that children with early-onset, severe disease die of disease complications long before the affected parent or grandparent is symptomatic. (See also Genetic Counseling.)

While attention has been focused on the phenomena of anticipation and trinucleotide repeat expansion, it is important to note that the number of trinucleotide repeats can also remain stable or even contract on transmission to subsequent generations.

Episodic Ataxias

The episodic ataxias are characterized by periods (i.e., minutes to hours) of unsteady gait often associated with nystagmus or dysarthria [Jen et al 2007]. Myokymia, vertigo, or hearing loss may occur in some of the subtypes. Permanent ataxia and even cerebellar atrophy may result late in the disease course.

Table 2.

Episodic Ataxias: Molecular Genetics & Clinical Features

DiseaseGene / Locus 1Distinguishing Clinical FeaturesReferences 2 / Selected OMIM Links
  • Gait ataxia
  • Myokymia
  • Attacks lasting seconds to minutes; startle or exercise induced
  • No vertigo
  • Gait ataxia
  • Nystagmus
  • Attacks lasting minutes to hours; posture change induced
  • Vertigo
  • Later, permanent ataxia
EA3 41q42
  • Adult onset
  • Vertigo
  • Tinnitus
Cader et al [2005]
/ 606554
EA4 5--
  • Adult onset
  • Cerebellar pathology documented
Steckley et al [2001], Jen et al [2007], Merrill et al [2016]
/ 606552
  • Childhood to adolescent onset
Escayg et al [2000], Jen et al [2007]
/ 613855
  • Seizures
  • Migraine
  • Childhood onset
de Vries et al [2009], Winter et al [2012]
/ 612656
  • Vertigo
  • Weakness
  • ? seizures
  • Childhood to adolescent onset
Kerber et al [2007]
/ 611907
Episodic ataxia with neonatal epilepsy SCN2A
  • Neonatal epilepsy
  • Later-onset episodic ataxia
  • Autism
  • Hypotonia
  • Dystonia
Schwarz et al [2016], Leach et al [2016]
CAPOS syndrome ATP1A3
  • Cerebellar ataxia
  • Areflexia
  • Pes cavus
  • Optic atrophy
  • Sensorineural hearing loss
  • Also alternating hemiplegia
See ATP1A3-Related Neurologic Disorders

See Episodic ataxia: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM.


Chromosome locus is given only when the gene is unknown.


References included when there is no GeneReview


EA2 is allelic to SCA6 (see Table 1) and familial hemiplegic migraine type 1.


A single family with EA3 (periodic vestibulocerebellar ataxia with defective smooth pursuit)


A single family with EA4 (episodic ataxia with vertigo and tinnitus) in North Carolina

Autosomal Recessive Hereditary Ataxias

The autosomal recessive hereditary ataxias are listed in Table 3:

  • The first part of the table lists those autosomal recessive ataxias that are relatively common (i.e., reported in >5 families; e.g., FRDA, AOA1, AOA2, and ATM) or treatable (e.g., CTX, Refsum syndrome, and AVED) or found more often in a specific ethnic group (e.g., ARSACS in French-Canadians).
  • The second part of the table lists autosomal recessive ataxias that are relatively uncommon (i.e., reported in 1-5 families) [Musselman et al 2014].

An overall review of these conditions can be found in Embiruçu et al [2009].

Note that autosomal recessive disorders associated with ataxia and/or cerebellar hypoplasia that are caused by biallelic pathogenic variants in one of many related genes are not included in this discussion or in Table 3. Examples include the following:

Table 3.

Autosomal Recessive Cerebellar Ataxias: Single-Gene Disorders

Gene / Locus 1DiseaseDistinguishing Clinical FeaturesOtherReferences / Selected OMIM Links
More common and/or treatable 2
ANO10 AR SCA 10 (SCAR10)
  • Downbeat nystagmus
  • Fasciculations
  • Spasticity
Vermeer et al [2010], Renaud et al [2014]
/ 613728
APTX Ataxia with oculomotor apraxia type 1 (AOA1)
  • Oculomotor apraxia
  • Choreoathetosis
  • Mild ID
  • Hypoalbuminemia
ATM Ataxia-telangiectasia
  • Telangiectasia
  • Immune deficiency
  • Cancer
  • Chromosome instability
  • ↑ alpha-fetoprotein
C10orf2 Infantile-onset SCA (IOSCA)
  • Peripheral neuropathy
  • Athetosis
  • Optic atrophy
  • Deafness
  • Ophthalmoplegia
CYP27A1 Cerebrotendinous xanthomatosis (CTX)
  • Thick tendons
  • Cognitive decline
  • Dystonia
  • White matter disease
  • Cataract
Treat w/chenodeoxycholic acid. 606530
FXN Friedreich ataxia (FRDA)
  • Hyporeflexia
  • Babinski responses
  • Sensory loss
  • Cardiomyopathy
Refsum disease
  • Neuropathy
  • Deafness
  • Ichthyosis
  • Retinopathy
Treat w/dietary phytanic acid. 266500
PNPLA6 Boucher-Neuhäuser syndrome
  • Vision loss
  • Delayed puberty
  • Spasticity
RFC1 Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (See RFC1 CANVAS / Spectrum Disorder.)
  • Late-onset ataxia
  • Peripheral neuropathy
  • Vestibular areflexia
Biallelic intronic AAGGG expansion Cortese et al [2019]
SACS AR spastic ataxia of Charlevoix-Saguenay (ARSACS)
  • Spasticity
  • Peripheral neuropathy
  • Retinal striation
SETX Ataxia with oculomotor apraxia type 2 (AOA2)
  • Cerebellar atrophy
  • Axonal sensorimotor neuropathy
  • Oculomotor apraxia
SIL1 Marinesco-Sjögren syndrome
  • ID
  • Cataract
  • Hypotonia
  • Myopathy
SLC52A2 Brown-Vialetto-Van Laere syndrome
  • Optic atrophy
  • Hearing loss
Treat w/riboflavin. 614707
Childhood-onset ataxia with blindness and deafness
  • Visual loss
  • Hearing loss
  • Peripheral neuropathy
Guissart et al [2016]
SNX14 AR SCA 20 (SCAR20)
  • Coarse facies
  • Cognitive deficency
  • Hearing loss
  • Seizures
  • Scolosis
Thomas et al [2014], Akizu et al [2015]
/ 616354
SYNE1 SYNE1-related AR cerebellar ataxia
  • French Canadian
  • Upper/lower motor neuron disease
Synofzik et al [2016]
TTPA Ataxia with vitamin E deficiency (AVED)
  • Similar to FRDA
  • Head titubation (28%)
Treat w/vitamin E. 277460
WFS1 Wolfram syndrome
  • Juvenile diabetes
  • Optic atrophy
  • Hearing loss
Less common 3
ABHD12 Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC)
  • Polyneuropathy
  • Hearing loss
  • Ataxia
  • Retinopathy
  • Cataract
Similar to RefsumFiskerstrand et al [2010], Chen et al [2013]
/ 612674
ACO2 Infantile cerebellar- retinal degeneration (ICRD)
  • Infant onset
  • Hypotonia
  • Seizures
  • ID
  • Retinopathy
Shortened life spanSpiegel et al [2012]
/ 614559
  • Mild psychomotor retardation
  • Seizures
  • ↑ plasma lactate
Treat w/CoQ10.Lagier-Tourenne et al [2008], Mollet et al [2008]
/ 612016
ATCAY Cayman ataxia
  • Grand Cayman Island
  • Psychomotor retardation
Bomar et al [2003]
/ 601238
ATG5 Congenital ataxia
  • DD
  • Non-progressive
Yapici & Eraksoy [2005], Kim et al [2016]
ATP8A2 Cerebellar ataxia, mental retardation, and dysequilibrium syndrome 4 (CAMRQ4)
  • Turkish
  • ID
  • Quadrupedal locomotor
Onat et al [2013]
/ 615268
CAPN1 Spastic ataxia
  • Spasticity
Mutation of CAPN1 also assoc w/SPG76 Shetty et al [2019]
CLCN2 Leukoencephalopathy with ataxia (LKPAT)
  • Spasticity
  • Retinopathy
Depienne et al [2013]
/ 615651
CLN5 Adult-onset AR ataxia associated with neuronal ceroid-lipofuscinosis 5 (CLN5)
  • Cognitive decline
  • Glaucoma
CWF19L1 AR ataxia (Turkish)
  • Turkish
  • DD
  • Cognitive impairment
Burns et al [2014]
FLVCR1 Posterior column ataxia with retinitis pigmentosa (AXPC1)
  • Spinal posterior column ataxia
  • Retinitis pigmentosa
Higgins et al [1999], Ishiura et al [2011]
/ 609033
GDAP2 Cerebellar ataxia
  • Adult onset
  • Spasticity
  • Dementia
Eidhof et al [2018]
GOSR2 Ramsay Hunt syndrome
  • Myoclonus epilepsy
Corbett et al [2011]
/ 614018
  • Delayed speech & cognitive development
  • Tonic upgaze
  • Retinopathy
Mutation of GRID2 also assoc w/AD inheritance 4Hills et al [2013], Van Schil et al [2015]
/ 616204
  • Roma
  • DDs
  • Intellectual deficit
  • Small brain
Guergueltcheva et al [2012]
/ 614831
KCNJ10 SeSAME syndrome
  • Deafness
  • ID
  • Electrolyte imbalance
Scholl et al [2009]
/ 612780
KIAA0226 AR SCA 15 (SCAR15)
  • Epilepsy
  • Cognitive deficits
Assoum et al [2013]
/ 615705
LAMA1 Cerebellar dysplasia
  • Cerebellar cysts
  • Retinopathy
Aldinger et al [2014]
/ 150320
MTCL1 Early-onset ataxia
  • Mild ID
  • Seizures
Krygier et al [2019]
PCDH12 Childhood-onset ataxia
  • Dystonia
  • Retinopathy
  • Facial dysmorphism
  • Seizures
Vineeth et al [2019]
  • Cognitive impairment
  • Dystonia (occasional)
  • Spasticity (occasional)
  • Mild-to-severe disability
  • Short stature (1 family)
  • Cerebellar granule cell loss
Jobling et al [2015], Choquet et al [2016] / 213200
PNKP Ataxia with oculomotor apraxia type 4 (AOA4)
  • Dystonia
  • Oculomotor apraxia
  • Polyneuropathy
  • Common in Portugal
Bras et al [2015]
/ 616267
POLG Mitochondrial recessive ataxia syndrome (MIRAS)
  • Neuropathy
  • Sensory ataxia
  • Myopathy
  • Progressive external opthalmoplegia
POLR3A or POLR3BCerebellar atrophy with hypomyelination
(see Pol III-Related Leukodystrophies)
  • Hypodontia
  • Hypogonadotropic hypogonadism
La Piana et al [2016]
PTF1A Pancreatic and cerebellar agenesis (PACA)
  • Neonatal diabetes
  • Cerebellar hypoplasia/agenesis
  • Dysmorphic facial features
Sellick et al [2004]
/ 609069
RNF216 Gordon Holmes syndrome
  • Dementia
  • Hypogonadotropic hypogonadism
  • Chorea
Margolin et al [2013], Santens et al [2015] / 212840
SLC9A1 Lichtenstein-Knorr syndrome
  • Severe sensorineural deafness
Turkish familyGuissart et al [2015]
/ 107310
SLC25A46 Pontocerebellar hypoplasia
  • Congenital
  • Lethal
  • Apnea
Wan et al [2016]
SNX14 AR SCA 20 (SCAR20)
  • Poor speech
  • Coarse face
  • ID
Al-Hashmi et al [2018]
/ 616354
  • Cognitive deficits
Mutation of SPTBN2 also assoc w/SCA5Lise et al [2012], Elsayed et al [2014]
/ 615386
SQSTM1 Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood onset (NADGP)
  • Early onset
  • Severe ataxia
  • Gaze palsy
  • Dyskinesia
  • Dystonia
  • Cognitive decline
Muto et al [2018] / 601530
  • Adolescent-onset ataxia w/cerebellar atrophy
  • Abnormal EMG/NCV
  • Cognitive impairment
Shi et al [2013], Depondt et al [2014], Synofzik et al [2014]
/ 615768
SYT14 AR SCA 11 (SCAR11)
  • Japanese
  • Psychomotor retardation
Doi et al [2011]
/ 614229
TDP1 SCA with axonal neuropathy (SCAN1)
  • Axonal sensorimotor neuropathy
  • Epilepsy
  • ID
  • Microcephaly
  • Fatigability
Hypersensitivity to DNA damage 616949
  • Hyperreflexia
  • DD
  • Diffuse cerebellar atrophy on MRI
Late-infantile neuronal ceroid-lipofuscinosis 2 (CLN2)Breedveld et al [2004], Sun et al [2013], Dy et al [2015]
/ 609270
TSFM AR cardiomyopathy with ataxia
  • Hypertrophic cardiomyopathy
  • Ataxia
  • Peripheral neuropathy
  • Optic atrophy
Leigh-like syndrome; elongation factor Ts, mitochondrialAhola et al [2014], Emperador et al [2016]
TXN2 Early-onset neurodegeneration
  • Epilepsy
  • Dystonia
  • Optic atrophy
  • Peripheral neuropathy
Holzerova et al [2016]
UBA5 (UFM1) Childhood-onset progressive ataxia
  • Cataract
Duan et al [2016]
  • Spasticity
  • Chorea/dystonia
  • Mitochondrial defects
Gauthier et al [2018], Seong et al [2018]
VLDLR VLDLR-associated cerebellar hypoplasia (CAMRQ1)
  • Hutterite
  • ID
  • Cerebral gyral simplification
VWA3B Cerebellar ataxia with intellectual disability
  • Spasticity
Kawarai et al [2016] / 616948
WDR73 Galloway-Mowat syndrome
(formerly AR SCA5 [SCAR5])
  • Optic atrophy
  • Skin abnormalities
  • Microcephaly
  • Seizures
  • Nephrotic syndrome
Jinks et al [2015]
/ 251300
  • Epilepsy
  • ID
  • Spasticity
Mallaret et al [2014]
/ 614322

AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; EMG = electromyogram; ID = intellectual disability; NCV = nerve conduction velocity; SCA = spinocerebellar ataxia; SPG = spastic paraplegia


Chromosome locus is given only when gene is unknown.


Reported in more than five families


"Less common" = reported in 1-5 families [Musselman et al 2014]


See Table 1.

Friedreich ataxia (FRDA) is the most common of the autosomal recessive ataxias. It generally begins in childhood with slowly progressive ataxia associated with depressed tendon reflexes and posterior column sensory loss.

  • About 25% of affected individuals have an "atypical" presentation with later onset (age >25 years), retained tendon reflexes, or unusually slow progression of disease.
  • The vast majority of individuals have a GAA triplet-repeat expansion in FXN; however, FRDA is not associated with anticipation [Dürr et al 1996]. Rare individuals have a pathogenic missense variant in one FXN allele with the GAA repeat in the other allele.

X-Linked Hereditary Ataxias

X-linked inheritance of cerebellar ataxia occurs (Table 4), but is quite uncommon except for fragile X tremor ataxia syndrome (FXTAS) [Zanni & Bertini 2011].

Table 4.

X-linked Cerebellar Ataxias: Molecular Genetics & Clinical Features

Gene / Locus 1DiseaseDistinguishing Clinical FeaturesOtherReferences 2 / Selected OMIM Links
ABCB7 X-linked sideroblastic anemia and ataxia
  • Early childhood onset
  • Anemia is asymptomatic.
Carrier females may have sideroblasts. 301310
ATP2B3 X-linked ataxia
  • Childhood onset
  • Hypotonia
Zanni et al [2012], Feyma et al [2016]
CASK CASK-related disorders
  • Cognitive deficiency
  • Microcephaly
  • Hypotonia
  • Optic nerve hypoplasia
Growth retardation 300749
  • Adult onset
Most common of the X-linked ataxias; occurs in male & female premutation carriers 300623
OPHN1 X-linked mental retardation with cerebellar hypoplasia and distinctive facial appearance
  • Infantile onset
  • Hypotonia
  • DD
  • Seizures
Zanni et al [2005]
/ 300486
SLC9A6 Christianson syndrome
  • Infantile onset
  • ID
  • Seizures
ID in carrier females;
may resemble Angelman syndrome
Xq25-q27.1X-linked spinocerebellar ataxia 5
  • Infantile onset
  • Cerebellar hypoplasia
Norwegian ancestryZanni et al [2008]
/ 300703

DD = developmental delay; FXTAS = fragile X-associated tremor/ataxia syndrome; ID = intellectual disability


Chromosome locus is given only when the gene is unknown.


References included when there is no GeneReview

Spastic Ataxias

The combination of spasticity with signs of cerebellar ataxia is relatively common and one or the other finding may predominate [de Bot et al 2012] (see Table 5). For example, ataxia and cerebellar atrophy both frequently occur in spastic paraplegia 7 (a form of hereditary spastic paraplegia), caused by pathogenic variants in SPG7 coding the protein paraplegin [van Gassen et al 2012].

Five disorders have specifically been designated spastic ataxia (SPAX). SPAX1 is inherited in an autosomal dominant manner and the other four are inherited in an autosomal recessive manner.

Table 5.

Disorders with Spasticity and Cerebellar Ataxia: Molecular Genetics & Clinical Features

Disease (MOI)GeneDistinguishing Clinical FeaturesOtherReferences / Selected OMIM Links
  • Initial progressive leg spasticity
  • Gait ataxia
Meijer et al [2002], Bourassa et al [2012]
/ 108600
  • Often w/childhood-onset tremor & dysmetria
Dor et al [2014]
/ 611302
  • Periventricular white matter changes
Bayat et al [2012]
/ 611390
  • Optic atrophy
Amish familyCrosby et al [2010]
/ 613672
  • Often w/peripheral neuropathy & epilepsy
Pierson et al [2011]
/ 614487
  • Vestibular failure
  • Cerebellar atrophy
Roxburgh et al [2013], Pfeffer et al [2015]

See Spastic ataxia: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM.


Allelic to SCA28 (see Table 1)

Ataxias with Mitochondrial Disorders

A progressive ataxia is sometimes associated with mutation of mitochondrial DNA (mtDNA) (see Mitochondrial Disorders Overview) including MERRF (myoclonic epilepsy with ragged red fibers), NARP (neuropathy, ataxia, and retinitis pigmentosa) [Finsterer 2009b], and Kearns-Sayre syndrome. Disorders of mtDNA are often associated with additional clinical manifestations, such as seizures, deafness, diabetes mellitus, cardiomyopathy, retinopathy, and short stature [Da Pozzo et al 2009]. Pfeffer et al [2012] report that missense pathogenic variants in MTATP6 can cause both childhood and adult-onset cerebellar ataxia sometimes associated with abnormal eye movements, dysarthria, weakness, axonal neuropathy, and hyperreflexia.

Note that many nuclear genes regulate mitochondrial function and may be mutated in autosomal recessive ataxias (See Mitochondrial Disorders Overview and Table 3, POLG).

Evaluation Strategy

Once a hereditary ataxia is considered in a proband (i.e., the index case in a family), the following approach can be used to determine the specific genetic cause to aid in discussions of prognosis and genetic counseling. Establishing the specific genetic cause of hereditary ataxia for a given individual usually involves a medical history, physical examination, neurologic examination, neuroimaging, three-generation family history, and molecular genetic testing.

Clinical Findings

Gait ataxia is the common manifestation of these disorders. Other common findings include nystagmus, dysarthria, and dysmetria. Brain imaging often shows cerebellar atrophy or hypoplasia. Age of onset varies widely, but is frequently in childhood in autosomal recessive ataxias. Intellectual disability, peripheral neuropathy, and retinal abnormalities may also occur.

Family History

A three-generation family history with attention to other relatives with neurologic signs and symptoms should be obtained. Documentation of relevant findings in relatives can be accomplished either through direct examination of those individuals or review of their medical records including the results of molecular genetic testing, neuroimaging studies, and autopsy examinations.


Non-DNA-based clinical tests are usually nonspecific except for rare instances such as vitamin E deficiency in AVED.

Molecular Genetic Testing

The ordering of molecular genetic tests and interpretation of results is complex and may require the support of an experienced laboratory, clinical geneticist, clinical geneticist, and genetic counselor.

Approaches to molecular genetic testing of a proband to consider are serial testing of single genes, multigene panel testing (simultaneous testing of multiple genes), and more comprehensive genomic testing (exome sequencing, genome sequencing, and mitochondrial sequencing).

Single-gene and multigene panel testing. In contrast to genomic testing, serial testing of single genes and multigene panel testing rely on the clinician developing a hypothesis about which specific gene or set of genes to test.

Hypotheses may be based on one or more of the following:

  • Mode of inheritance
  • Distinguishing clinical features
  • Other discriminating features (listed in the Other column of the tables) including:
    • Apparent anticipation for a nucleotide-repeat disorder;
    • Ethnicity (country/region of origin);
    • Distinctive age of onset;
    • Shortened life span;
    • Treatment available;
    • Specific neuropathologic findings.

Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.

Németh et al [2013] studied the clinical utility of a multigene panel for diagnosis of neurologic disorders using the hereditary ataxias as a model. Using next-generation sequencing they searched for small, intragenic pathogenic variants in 58 known human ataxia genes in 50 individuals with ataxia and a wide range of findings whose testing for SCA1, 2, 3, 6, 7, and Friedreich ataxia had been normal.

  • Pathogenic variants were found in eight different genes: PRKCG PRKCG, TTBK2, SETX, SPTBN2, SACS, MRE11, KCNC3, and DARS2.
  • The overall detection rate was 18% and varied from 8.3% in those with adult-onset progressive disorders to 40% in those with childhood or adolescent onset progressive disorders.
  • The highest detection rate was in those with adolescent onset and a positive family history (75%).

This study demonstrated that this multigene panel was efficient and cost effective and enabled a molecular diagnosis in many refractory cases.

For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.

More comprehensive genomic testing (when available) including exome sequencing, genome sequencing, and mitochondrial sequencing may be considered if single-gene testing (and/or use of a multigene panel) fails to confirm a diagnosis in an individual with features of a hereditary ataxia. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene that results in a similar clinical presentation).

For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.

Mode of Inheritance

More than one affected family member

Simplex case

Distinguishing Clinical Features

Distinguishing clinical findings exist for a number of inherited ataxias:

  • Because of extensive clinical overlap between all forms of autosomal dominant hereditary ataxia, it is difficult in any given individual with ataxia and a family history consistent with autosomal dominant inheritance to establish a diagnosis without molecular genetic testing. Note that retinal disease suggests SCA7, Portugese ancestry suggests SCA3, seizures and Amerindian ancestry suggests SCA10, and chorea suggests SCA17 or DRPLA [Ashizawa et al 2013]. See Table 1.
  • Clinical findings such as intellectual disability, seizures, eye abnormalities, or peripheral neuropathy may help distinguish between some of the autosomal recessive ataxias. See Table 3.
  • Distinct brief (minutes to hours) episodes of ataxia separated by normal function strongly suggests an episodic ataxia. See Table 2.
  • Prominent spasticity suggests one of the spastic ataxias. See Table 5.

In the absence of distinguishing clinical features, multigene panel testing may be considered. Panels may be oriented around a specific, relatively small subset of hereditary ataxias (e.g., the most common autosomal dominant spinocerebellar ataxias) or may include a broad range of disorders (e.g., all known hereditary ataxias).


Ethnicity. Single-gene testing may be considered on the basis of an individual's ethnic background

Prevalence. Prevalence of a disorder can be used to order in which a series of single-gene testing is performed (i.e., test in order of most common to least common hereditary ataxia) or choice of a multigene panel (i.e., selecting a panel including only the five or six most common hereditary ataxias).

The most common adult-onset autosomal dominant ataxias are SCA1, SCA2, SCA3, SCA6, and SCA7, and the most common autosomal recessive ataxias (which are usually of childhood onset) are Friedreich ataxia, AOA1, AOA2, and ataxia-telangiectasia.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members; it is not meant to address all personal, cultural, or ethical issues that may arise or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

This GeneReview includes hereditary ataxias that may be inherited in an autosomal dominant manner, an autosomal recessive manner, or an X-linked recessive manner. (Hereditary ataxias caused by mutation of mitochondrial DNA are discussed in Mitochondrial Disorders Overview.)

If a proband has a specific syndrome associated with ataxia (e.g., Friedreich ataxia or FXTAS), counseling for that condition is indicated.

Autosomal Dominant Inheritance – Risk to Family Members

Parents of a proband

  • Most individuals diagnosed as having autosomal dominant ataxia have an affected parent, although occasionally the family history is negative.
  • Family history may appear to be negative because of early death of a parent, failure to recognize autosomal dominant ataxia in family members, late onset in a parent, reduced penetrance of the pathogenic allele in an asymptomatic parent, or de novo mutation.

Sibs of a proband

  • The risk to sibs depends on the genetic status of the proband's parents.
  • If one of the proband's parents has a pathogenic variant, the risk to the sibs of inheriting the pathogenic variant is 50%.

Offspring of a proband. Individuals with autosomal dominant ataxia have a 50% chance of transmitting the pathogenic variant to each child.

Other family members. The risk to other family members depends on the status of the proband's parents. If a parent is affected, his or her family members may be at risk.

Autosomal Recessive Inheritance

Risk to Family Members

Parents of a proband

  • The parents are obligate heterozygotes and therefore carry a single copy of a pathogenic variant.
  • Heterozygotes are asymptomatic.

Sibs of a proband

  • At conception, each sib of a proband has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.

Offspring of a proband. All offspring are obligate heterozygotes (carriers) for a pathogenic variant.

Other family members. Each sib of the proband's parents is at a 50% risk of being a carrier.

Carrier (Heterozygote) Detection

Carrier testing for at-risk relatives requires prior identification of the pathogenic variants in the family.

X-Linked Inheritance

Risk to Family Members

Parents of a proband

  • The father of an affected male will not have the disease nor will he be a carrier of the pathogenic variant.
  • Women who have an affected son and another affected male relative are obligate heterozygotes.

Sibs of a proband

  • The risk to sibs depends on the carrier status of the mother.
  • If the mother of the proband has a pathogenic variant, the chance of transmitting it in each pregnancy is 50%. Male sibs who inherit the pathogenic variant will be affected; female sibs who inherit the pathogenic variant will be carriers and will usually not be affected.
  • If the proband represents a simplex case (i.e., a single occurrence in a family) and if the pathogenic variant cannot be detected in the leukocyte DNA of the mother, the risk to sibs is low but greater than that of the general population because of the possibility of maternal germline mosaicism.

Offspring of a proband. All the daughters of an affected male are carriers; none of his sons will be affected.

Other family members. The proband's maternal aunts may be at risk of being carriers and the aunts' offspring, depending on their gender, may be at risk of being carriers or of being affected.

Heterozygote (Carrier) Detection

Carrier testing for females at risk for an X-linked disorder requires prior identification of the pathogenic variant in the family.

Related Genetic Counseling Issues

Testing of at-risk asymptomatic adult relatives of individuals with hereditary ataxia is possible after molecular genetic testing has identified the specific disorder and pathogenic variant(s) in the family. Such testing should be performed in the context of formal genetic counseling.

In general, molecular genetic test results are not useful in predicting age of onset, severity, type of symptoms, or rate of progression in asymptomatic individuals.

Molecular genetic testing of asymptomatic individuals younger than age 18 years who are at risk for adult-onset disorders for which no treatment exists is not considered appropriate, primarily because it negates the autonomy of the child with no compelling benefit. Further, concern exists regarding the potential unhealthy adverse effects that such information may have on family dynamics, the risk of discrimination and stigmatization in the future, and the anxiety that such information may cause.

See also the National Society of Genetic Counselors position statement on genetic testing of minors for adult-onset conditions and the American Academy of Pediatrics and American College of Medical Genetics and Genomics policy statement: ethical and policy issues in genetic testing and screening of children.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing and Preimplantation Genetic Testing

Once the pathogenic variant(s) have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for hereditary ataxia are possible. However, in general, age of onset, severity of disease, specific symptoms, and rate of disease progression are variable and cannot be accurately predicted by the family history or molecular genetic testing. See Causes, ADCA, Nucleotide-repeat disorders.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. While most centers would consider use of prenatal testing to be a personal decision, discussion of these issues may be helpful.


GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • Ataxia UK
    Lincoln House
    1-3 Brixton Road
    London SW9 6DE
    United Kingdom
    Phone: 0845 644 0606 (helpline); 020 7582 1444 (office); +44 (0) 20 7582 1444 (from abroad)
  • National Ataxia Foundation
    2600 Fernbrook Lane
    Suite 119
    Minneapolis MN 55447
    Phone: 763-553-0020
  • Spanish Ataxia Federation (FEDAES)
    Phone: 34 983 278 029; 34 985 097 152; 34 634 597 503
  • Spinocerebellar Ataxia: Making an Informed Choice about Genetic Testing
    Booklet providing information about Spinocerebellar Ataxia
  • Associazione Nazionale SiIndromi Atassiche (A.I.S.A.) O.N.L.U.S.
    Via Sara 12
    Fax: 39 178 2279678
  • euro-ATAXIA (European Federation of Hereditary Ataxias)
    Ataxia UK
    Lincoln House, Kennington Park, 1-3 Brixton Road
    London SW9 6DE
    United Kingdom
    Phone: +44 (0) 207 582 1444
  • NCBI Genes and Disease


Treatment of Manifestations

Management of ataxias is usually directed at providing assistance for coordination problems through established methods of rehabilitation medicine and occupational and physical therapy.

Canes, walkers, and wheelchairs are useful for gait ataxia.

Special devices are available to assist with handwriting, buttoning, and use of eating utensils.

Speech therapy may benefit persons with dysarthria. Computer devices are available to assist persons with severe speech deficits.

Prevention of Primary Manifestations

With the exception of AVED, Refsum syndrome, CTX, and CoQ10 deficiency, no specific treatments exist for hereditary ataxia.


Published Guidelines / Consensus Statements

  • Committee on Bioethics, Committee on Genetics, and American College of Medical Genetics and Genomics Social, Ethical, Legal Issues Committee. Ethical and policy issues in genetic testing and screening of children. Available online. 2013. Accessed 2-4-21.
  • National Society of Genetic Counselors. Position statement on genetic testing of minors for adult-onset conditions. Available online. 2018. Accessed 2-4-21.

Literature Cited

  • Abele M, Burk K, Schols L, Schwartz S, Besenthal I, Dichgans J, Zuhlke C, Riess O, Klockgether T. The aetiology of sporadic adult-onset ataxia. Brain. 2002;125:961–8. [PubMed: 11960886]
  • Ahmed MY, Chioza BA, Rajab A, Schmitz-Abe K, Al-Khayat A, Al-Turki S, Baple EL, Patton MA, Al-Memar AY, Hurles ME, Partlow JN, Hill RS, Evrony GD, Servattalab S, Markianos K, Walsh CA, Crosby AH, Mochida GH. Loss of PCLO function underlies pontocerebellar hypoplasia type III. Neurology. 2015;84:1745–50. [PMC free article: PMC4424132] [PubMed: 25832664]
  • Ahola S, Isohanni P, Euro L, Brilhante V, Palotie A, Pihko H, Lönnqvist T, Lehtonen T, Laine J, Tyynismaa H, Suomalainen A. Mitochondrial EFTs defects in juvenile-onset Leigh disease, ataxia, neuropathy, and optic atrophy. Neurology. 2014;83:743–51. [PMC free article: PMC4150129] [PubMed: 25037205]
  • Akizu N, Cantagrel V, Zaki MS, Al-Gazali L, Wang X, Rosti RO, Dikoglu E, Gelot AB, Rosti B, Vaux KK, Scott EM, Silhavy JL, Schroth J, Copeland B, Schaffer AE, Gordts PL, Esko JD, Buschman MD, Field SJ, Napolitano G, Abdel-Salam GM, Ozgul RK, Sagıroglu MS, Azam M, Ismail S, Aglan M, Selim L, Mahmoud IG, Abdel-Hadi S, Badawy AE, Sadek AA, Mojahedi F, Kayserili H, Masri A, Bastaki L, Temtamy S, Müller U, Desguerre I, Casanova JL, Dursun A, Gunel M, Gabriel SB, de Lonlay P, Gleeson JG. Biallelic mutations in SNX14 cause a syndromic form of cerebellar atrophy and lysosome-autophagosome dysfunction. Nat Genet. 2015;47:528–34. [PMC free article: PMC4414867] [PubMed: 25848753]
  • Aldinger KA, Mosca SJ, Tétreault M, Dempsey JC, Ishak GE, Hartley T, Phelps IG, Lamont RE, O'Day DR, Basel D, Gripp KW, Baker L, Stephan MJ, Bernier FP, Boycott KM, Majewski J., University of Washington Center for Mendelian Genomics. Care4Rare Canada, Parboosingh JS, Innes AM, Doherty D. Mutations in LAMA1 cause cerebellar dysplasia and cysts with and without retinal dystrophy. Am J Hum Genet. 2014;95:227–34. [PMC free article: PMC4129402] [PubMed: 25105227]
  • Al-Hashmi N, Mohammed M, Al-Kathir S, Al-Yarubi N, Scott P. Exome sequencing identifies a novel sorting nexin 14 gene mutation causing cerebellar atrophy and intellectual disability. Case Rep Genet. 2018;2018:6737938. [PMC free article: PMC6220403] [PubMed: 30473892]
  • Ashizawa T, Figueroa KP, Perlman SL, Gomez CM, Wilmot GR, Schmahmann JD, Ying SH, Zesiewicz TA, Paulson HL, Shakkottai VG, Bushara KO, Kuo SH, Geschwind MD, Xia G, Mazzoni P, Krischer JP, Cuthbertson D, Holbert AR, Ferguson JH, Pulst SM, Subramony S. Clinical characteristics of patients with spinocerebellar ataxias 1, 2, 3 and 6 in the US; a prospective observational study. Orphanet J Rare Dis. 2013;2013;8:177. [PMC free article: PMC3843578] [PubMed: 24225362]
  • Assoum M, Salih MA, Drouot N, Hnia K, Martelli A, Koenig M. The Salih ataxia mutation impairs Rubicon endosomal localization. Cerebellum. 2013;12:835–40. [PubMed: 23728897]
  • Bakalkin G, Watanabe H, Jezierska J, Depoorter C, Verschuuren-Bemelmans C, Bazov I, Artemenko KA, Yakovleva T, Dooijes D, Van de Warrenburg BP, Zubarev RA, Kremer B, Knapp PE, Hauser KF, Wijmenga C, Nyberg F, Sinke RJ, Verbeek DS. Prodynorphin mutations cause the neurodegenerative disorder spinocerebellar ataxia type 23. Am J Hum Genet. 2010;87:593–603. [PMC free article: PMC2978951] [PubMed: 21035104]
  • Bayat V, Thiffault I, Jaiswal M, Tétreault M, Donti T, Sasarman F, Bernard G, Demers-Lamarche J, Dicaire MJ, Mathieu J, Vanasse M, Bouchard JP, Rioux MF, Lourenco CM, Li Z, Haueter C, Shoubridge EA, Graham BH, Brais B, Bellen HJ. Mutations in the mitochondrial methionyl-tRNA synthetase cause a neurodegenerative phenotype in flies and a recessive ataxia (ARSAL) in humans. PLoS Biol. 2012;10:e1001288. [PMC free article: PMC3308940] [PubMed: 22448145]
  • Bomar JM, Benke PJ, Slattery EL, Puttagunta R, Taylor LP, Seong E, Nystuen A, Chen W, Albin RL, Patel PD, Kittles RA, Sheffield VC, Burmeister M. Mutations in a novel gene encoding a CRAL-TRIO domain cause human Cayman ataxia and ataxia/dystonia in the jittery mouse. Nat Genet. 2003;35:264–9. [PubMed: 14556008]
  • Bourassa CV, Meijer IA, Merner ND, Grewal KK, Stefanelli MG, Hodgkinson K, Ives EJ, Pryse-Phillips W, Jog M, Boycott K, Grimes DA, Goobie S, Leckey R, Dion PA, Rouleau GA. VAMP1 mutation causes dominant hereditary spastic ataxia in Newfoundland families. Am J Hum Genet. 2012;91:548–52. [PMC free article: PMC3511983] [PubMed: 22958904]
  • Bras J, Alonso I, Barbot C, Costa MM, Darwent L, Orme T, Sequeiros J, Hardy J, Coutinho P, Guerreiro R. Mutations in PNKP cause recessive ataxia with oculomotor apraxia type 4. Am J Hum Genet. 2015;96:474–9. [PMC free article: PMC4375449] [PubMed: 25728773]
  • Breedveld GJ, van Wetten B, te Raa GD, Brusse E, van Swieten JC, Oostra BA, Maat-Kievit JA. A new locus for a childhood onset, slowly progressive autosomal recessive spinocerebellar ataxia maps to chromosome 11p15. J Med Genet. 2004;41:858–66. [PMC free article: PMC1735612] [PubMed: 15520412]
  • Brkanac Z, Fernandez M, Matsushita M, Lipe H, Wolff J, Bird TD, Raskind WH. Autosomal dominant sensory/motor neuropathy with Ataxia (SMNA): Linkage to chromosome 7q22-q32. Am J Med Genet. 2002;114:450–7. [PubMed: 11992570]
  • Brkanac Z, Spencer D, Shendure J, Robertson PD, Matsushita M, Vu T, Bird TD, Olson MV, Raskind WH. IFRD1 is a candidate gene for SMNA on chromosome 7q22-q23. Am J Hum Genet. 2009;84:692–7. [PMC free article: PMC2680994] [PubMed: 19409521]
  • Brusco A, Gellera C, Cagnoli C, Saluto A, Castucci A, Michielotto C, Fetoni V, Mariotti C, Migone N, Di Donato S, Taroni F. Molecular genetics of hereditary spinocerebellar ataxia: mutation analysis of spinocerebellar ataxia genes and CAG/CTG repeat expansion detection in 225 Italian families. Arch Neurol. 2004;61:727–33. [PubMed: 15148151]
  • Brusse E, de Koning I, Maat-Kievit A, Oostra BA, Heutink P, van Swieten JC. Spinocerebellar ataxia associated with a mutation in the fibroblast growth factor 14 gene (SCA27): A new phenotype. Mov Disord. 2006;21:396–401. [PubMed: 16211615]
  • Bürk K, Zuhlke C, Konig IR, Ziegler A, Schwinger E, Globas C, Dichgans J, Hellenbroich Y. Spinocerebellar ataxia type 5: clinical and molecular genetic features of a German kindred. Neurology. 2004;62:327–9. [PubMed: 14745083]
  • Burns R, Majczenko K, Xu J, Peng W, Yapici Z, Dowling JJ, Li JZ, Burmeister M. Homozygous splice mutation in CWF19L1 in a Turkish family with recessive ataxia syndrome. Neurology. 2014;83:2175–82. [PMC free article: PMC4276403] [PubMed: 25361784]
  • Cader MZ, Steckley JL, Dyment DA, McLachlan RS, Ebers GC. A genome-wide screen and linkage mapping for a large pedigree with episodic ataxia. Neurology. 2005;65:156–8. [PubMed: 16009908]
  • Cadieux-Dion M, Turcotte-Gauthier M, Noreau A, Martin C, Meloche C, Gravel M, Drouin CA, Rouleau GA, Nguyen DK, Cossette P. Expanding the clinical phenotype associated with ELOVL4 mutation: study of a large French-Canadian family with autosomal dominant spinocerebellar ataxia and erythrokeratodermia. JAMA Neurol. 2014;71:470–5. [PubMed: 24566826]
  • Chen DH, Naydenov A, Blankman JL, Mefford HC, Davis M, Sul Y, Barloon AS, Bonkowski E, Wolff J, Matsushita M, Smith C, Cravatt BF, Mackie K, Raskind WH, Stella N, Bird TD. Two novel mutations in ABHD12: expansion of the mutation spectrum in PHARC and assessment of their functional effects. Hum Mutat. 2013;34:1672–8. [PMC free article: PMC3855015] [PubMed: 24027063]
  • Choquet K, Zurita-Rendón O, La Piana R, Yang S, Dicaire MJ. Care4Rare Consortium, Boycott KM, Majewski J, Shoubridge EA, Brais B, Tétreault M. Autosomal recessive cerebellar ataxia caused by a homozygous mutation in PMPCA. Brain. 2016;139:e19. [PubMed: 26657514]
  • Chung MY, Lu YC, Cheng NC, Soong BW. A novel autosomal dominant spinocerebellar ataxia (SCA22) linked to chromosome 1p21-q23. Brain. 2003;126:1293–9. [PubMed: 12764052]
  • Chung MY, Soong BW. Reply to: SCA-19 and SCA-22: evidence for one locus with a worldwide distribution. Brain. 2004;127:E7. [PubMed: 14679032]
  • Corbett MA, Schwake M, Bahlo M, Dibbens LM, Lin M, Gandolfo LC, Vears DF, O'Sullivan JD, Robertson T, Bayly MA, Gardner AE, Vlaar AM, Korenke GC, Bloem BR, de Coo IF, Verhagen JM, Lehesjoki AE, Gecz J, Berkovic SF. A mutation in the Golgi Qb-SNARE gene GOSR2 causes progressive myoclonus epilepsy with early ataxia. Am J Hum Genet. 2011;88:657–63. [PMC free article: PMC3146720] [PubMed: 21549339]
  • Corcia P, Vourc'h P, Guennoc AM, Del Mar Amador M, Blasco H, Andres C, Couratier P, Gordon PH, Meininger V. Pure cerebellar ataxia linked to large C9orf72 repeat expansion. Amyotroph Lateral Scler Frontotemporal Degener. 2016;17:301–3. [PubMed: 26609732]
  • Cortese A, Simone R, Sullivan R, Vandrovcova J, Tariq H, Yan YW, Humphrey J, Jaunmuktane Z, Sivakumar P, Polke J, Ilyas M, Tribollet E, Tomaselli PJ, Devigili G, Callegari I, Versino M, Salpietro V, Efthymiou S, Kaski D, Wood NW, Andrade NS, Buglo E, Rebelo A, Rossor AM, Bronstein A, Fratta P, Marques WJ, Züchner S, Reilly MM, Houlden H. Biallelic expansion of an intronic repeat in RFC1 is a common cause of late-onset ataxia. Nat Genet. 2019;51:649–58. [PMC free article: PMC6709527] [PubMed: 30926972]
  • Coutelier M, Blesneac I, Monteil A, Monin ML, Ando K, Mundwiller E, Brusco A, Le Ber I, Anheim M, Castrioto A, Duyckaerts C, Brice A, Durr A, Lory P, Stevanin G. A Recurrent Mutation in CACNA1G Alters Cav3.1 T-Type Calcium-Channel Conduction and Causes Autosomal-Dominant Cerebellar Ataxia. Am J Hum Genet. 2015a;97:726–37. [PMC free article: PMC4667105] [PubMed: 26456284]
  • Coutelier M, Burglen L, Mundwiller E, Abada-Bendib M, Rodriguez D, Chantot-Bastaraud S, Rougeot C, Cournelle MA, Milh M, Toutain A, Bacq D, Meyer V, Afenjar A, Deleuze JF, Brice A, Héron D, Stevanin G, Durr A. GRID2 mutations span from congenital to mild adult-onset cerebellar ataxia. Neurology. 2015b;84:1751–9. [PubMed: 25841024]
  • Crosby AH, Patel H, Chioza BA, Proukakis C, Gurtz K, Patton MA, Sharifi R, Harlalka G, Simpson MA, Dick K, Reed JA, Al-Memar A, Chrzanowska-Lightowlers ZM, Cross HE, Lightowlers RN. Defective mitochondrial mRNA maturation is associated with spastic ataxia. Am J Hum Genet. 2010;87:655–60. [PMC free article: PMC2978972] [PubMed: 20970105]
  • Da Pozzo P, Cardaioli E, Malfatti E, Gallus GN, Malandrini A, Gaudiano C, Berti G, Invernizzi F, Zeviani M, Federico A. A novel mutation in the mitochondrial tRNA(Pro) gene associated with late-onset ataxia, retinitis pigmentosa, deafness, leukoencephalopathy and complex I deficiency. Eur J Hum Genet. 2009;17:1092–6. [PMC free article: PMC2986557] [PubMed: 19223931]
  • de Bot ST, Willemsen MA, Vermeer S, Kremer HP, van de Warrenburg BP. Reviewing the genetic causes of spastic-ataxias. Neurology. 2012;79:1507–14. [PubMed: 23033504]
  • de Vries B, Mamsa H, Stam AH, Wan J, Bakker SL, Vanmolkot KR, Haan J, Terwindt GM, Boon EM, Howard BD, Frants RR, Baloh RW, Ferrari MD, Jen JC, van den Maagdenberg AM. Episodic ataxia associated with EAAT1 mutation C186S affecting glutamate reuptake. Arch Neurol. 2009;66:97–101. [PubMed: 19139306]
  • Delplanque J, Devos D, Huin V, Genet A, Sand O, Moreau C, Goizet C, Charles P, Anheim M, Monin ML, Buée L, Destée A, Grolez G, Delmaire C, Dujardin K, Dellacherie D, Brice A, Stevanin G, Strubi-Vuillaume I, Dürr A, Sablonnière B. TMEM240 mutations cause spinocerebellar ataxia 21 with mental retardation and severe cognitive impairment. Brain. 2014;137:2657–63. [PubMed: 25070513]
  • Depienne C, Bugiani M, Dupuits C, Galanaud D, Touitou V, Postma N, van Berkel C, Polder E, Tollard E, Darios F, Brice A, de Die-Smulders CE, Vles JS, Vanderver A, Uziel G, Yalcinkaya C, Frints SG, Kalscheuer VM, Klooster J, Kamermans M, Abbink TE, Wolf NI, Sedel F, van der Knaap MS. Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study. Lancet Neurol. 2013;12:659–68. [PubMed: 23707145]
  • Depondt C, Donatello S, Simonis N, Rai M, van Heurck R, Abramowicz M, D'Hooghe M, Pandolfo M. Autosomal recessive cerebellar ataxia of adult onset due to STUB1 mutations. Neurology. 2014;2014;82:1749–50. [PubMed: 24719489]
  • Devos D, Schraen-Maschke S, Vuillaume I, Dujardin K, Naze P, Willoteaux C, Destee A, Sablonniere B. Clinical features and genetic analysis of a new form of spinocerebellar ataxia. Neurology. 2001;56:234–8. [PubMed: 11160961]
  • Di Gregorio E, Borroni B, Giorgio E, Lacerenza D, Ferrero M, Lo Buono N, Ragusa N, Mancini C, Gaussen M, Calcia A, Mitro N, Hoxha E, Mura I, Coviello DA, Moon YA, Tesson C, Vaula G, Couarch P, Orsi L, Duregon E, Papotti MG, Deleuze JF, Imbert J, Costanzi C, Padovani A, Giunti P, Maillet-Vioud M, Durr A, Brice A, Tempia F, Funaro A, Boccone L, Caruso D, Stevanin G, Brusco A. ELOVL5 mutations cause spinocerebellar ataxia 38. Am J Hum Genet. 2014;95:209–17. [PMC free article: PMC4129408] [PubMed: 25065913]
  • Doi H, Yoshida K, Yasuda T, Fukuda M, Fukuda Y, Morita H, Ikeda S, Kato R, Tsurusaki Y, Miyake N, Saitsu H, Sakai H, Miyatake S, Shiina M, Nukina N, Koyano S, Tsuji S, Kuroiwa Y, Matsumoto N. Exome sequencing reveals a homozygous SYT14 mutation in adult-onset, autosomal-recessive spinocerebellar ataxia with psychomotor retardation. Am J Hum Genet. 2011;89:320–7. [PMC free article: PMC3155161] [PubMed: 21835308]
  • Dor T, Cinnamon Y, Raymond L, Shaag A, Bouslam N, Bouhouche A, Gaussen M, Meyer V, Durr A, Brice A, Benomar A, Stevanin G, Schuelke M, Edvardson S. KIF1C mutations in two families with hereditary spastic paraparesis and cerebellar dysfunction. J Med Genet. 2014;51:137–42. [PubMed: 24319291]
  • Dryer SE, Lhuillier L, Cameron JS, Martin-Caraballo M. Expression of K(Ca) channels in identified populations of developing vertebrate neurons: role of neurotrophic factors and activity. J Physiol Paris. 2003;97:49–58. [PubMed: 14706690]
  • Duan R, Shi Y, Yu L, Zhang G, Li J, Lin Y, Guo J, Wang J, Shen L, Jiang H, Wang G, Tang B. UBA5 mutations cause a new form of autosomal recessive cerebellar ataxia. PLoS One. 2016;11:e0149039. [PMC free article: PMC4752235] [PubMed: 26872069]
  • Duarri A, Jezierska J, Fokkens M, Meijer M, Schelhaas HJ, den Dunnen WF, van Dijk F, Verschuuren-Bemelmans C, Hageman G, van de Vlies P, Küsters B, van de Warrenburg BP, Kremer B, Wijmenga C, Sinke RJ, Swertz MA, Kampinga HH, Boddeke E, Verbeek DS. Mutations in potassium channel kcnd3 cause spinocerebellar ataxia type 19. Ann Neurol. 2012;72:870–80. [PubMed: 23280838]
  • Dudding TE, Friend K, Schofield PW, Lee S, Wilkinson IA, Richards RI. Autosomal dominant congenital non-progressive ataxia overlaps with the SCA15 locus. Neurology. 2004;63:2288–92. [PubMed: 15623688]
  • Dürr A. Autosomal dominant cerebellar ataxias: polyglutamine expansions and beyond. Lancet Neurol. 2010;9:885–94. [PubMed: 20723845]
  • Dürr A, Cossee M, Agid Y, Campuzano V, Mignard C, Penet C, Mandel JL, Brice A, Koenig M. Clinical and genetic abnormalities in patients with Friedreich's ataxia. N Engl J Med. 1996;335:1169–75. [PubMed: 8815938]
  • Dy ME, Sims KB, Friedman J. TPP1 deficiency: Rare cause of isolated childhood-onset progressive ataxia. Neurology. 2015;85:1259–61. [PubMed: 26224725]
  • Edener U, Bernard V, Hellenbroich Y, Gillessen-Kaesbach G, Zühlke C. Two dominantly inherited ataxias linked to chromosome 16q22.1: SCA4 and SCA31 are not allelic. J Neurol. 2011;258:1223–7. [PubMed: 21267591]
  • Eidhof I, Baets J, Kamsteeg EJ, Deconinck T, van Ninhuijs L, Martin JJ, Schüle R, Züchner S, De Jonghe P, Schenck A, van de Warrenburg BP. AP2 mutations implicate susceptibility to cellular stress in a new form of cerebellar ataxia. Brain. 2018;141:2592–604. [PMC free article: PMC7534050] [PubMed: 30084953]
  • Elsayed SM, Heller R, Thoenes M, Zaki MS, Swan D, Elsobky E, Zühlke C, Ebermann I, Nürnberg G, Nürnberg P, Bolz HJ. Autosomal dominant SCA5 and autosomal recessive infantile SCA are allelic conditions resulting from SPTBN2 mutations. Eur J Hum Genet. 2014;22:286–8. [PMC free article: PMC3895650] [PubMed: 23838597]
  • Embiruçu EK, Martyn ML, Schlesinger D, Kok F. Autosomal recessive ataxias: 20 types, and counting. Arq Neuropsiquiatr. 2009;67:1143–56. [PubMed: 20069237]
  • Emperador S, Bayona-Bafaluy MP, Fernández-Marmiesse A, Pineda M, Felgueroso B, López-Gallardo E, Artuch R, Roca I, Ruiz-Pesini E, Couce ML, Montoya J. Molecular-genetic characterization and rescue of a TSFM mutation causing childhood-onset ataxia and nonobstructive cardiomyopathy. Eur J Hum Genet. 2016;25:153–6. [PMC free article: PMC5159760] [PubMed: 27677415]
  • Escayg A, De Waard M, Lee DD, Bichet D, Wolf P, Mayer T, Johnston J, Baloh R, Sander T, Meisler MH. Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. Am J Hum Genet. 2000;66:1531–9. [PMC free article: PMC1378014] [PubMed: 10762541]
  • Feyma T, Ramsey K, Huentelman MJ, Craig DW, Padilla-Lopez S, Narayanan V, Kruer MC. Dystonia in ATP2B3-associated X-linked spinocerebellar ataxia. Mov Disord. 2016;31:1752–3. [PMC free article: PMC5380585] [PubMed: 27653636]
  • Finsterer J. Ataxias with autosomal, X-chromosomal or maternal inheritance. Can J Neurol Sci. 2009a;36:409–28. [PubMed: 19650351]
  • Finsterer J. Mitochondrial ataxias. Can J Neurol Sci. 2009b;36:543–53. [PubMed: 19831121]
  • Fiskerstrand T, Hmida-Ben Brahim D, Johansson S, M'zahem A, Haukanes BI, Drouot N, Zimmermann J, Cole AJ, Vedeler C, Bredrup C, Assoum M, Tazir M, Klockgether T, Hamri A, Steen VM, Boman H, Bindoff LA, Koenig M, Knappskog PM. Mutations in ABHD12 cause the neurodegenerative disease PHARC: An inborn error of endocannabinoid metabolism. Am J Hum Genet. 2010;87:410–7. [PMC free article: PMC2933347] [PubMed: 20797687]
  • Flanigan K, Gardner K, Alderson K, Galster B, Otterud B, Leppert MF, Kaplan C, Ptacek LJ. Autosomal dominant spinocerebellar ataxia with sensory axonal neuropathy (SCA4): clinical description and genetic localization to chromosome 16q22.1. Am J Hum Genet. 1996;59:392–9. [PMC free article: PMC1914712] [PubMed: 8755926]
  • Gauthier J, Meijer IA, Lessel D, Mencacci NE, Krainc D, Hempel M, Tsiakas K, Prokisch H, Rossignol E, Helm MH, Rodan LH, Karamchandani J, Carecchio M, Lubbe SJ, Telegrafi A, Henderson LB, Lorenzo K, Wallace SE, Glass IA, Hamdan FF, Michaud JL, Rouleau GA, Campeau PM. Recessive mutations in VPS13D cause childhood onset movement disorders. Ann Neurol. 2018;83:1089–95. [PubMed: 29518281]
  • Guergueltcheva V, Azmanov DN, Angelicheva D, Smith KR, Chamova T, Florez L, Bynevelt M, Nguyen T, Cherninkova S, Bojinova V, Kaprelyan A, Angelova L, Morar B, Chandler D, Kaneva R, Bahlo M, Tournev I, Kalaydjieva L. Autosomal-recessive congenital cerebellar ataxia is caused by mutations in metabotropic glutamate receptor 1. Am J Hum Genet. 2012;91:553–64. [PMC free article: PMC3511982] [PubMed: 22901947]
  • Guissart C, Drouot N, Oncel I, Leheup B, Gershoni-Barush R, Muller J, Ferdinandusse S, Larrieu L, Anheim M, Arslan EA, Claustres M, Tranchant C, Topaloglu H, Koenig M. Genes for spinocerebellar ataxia with blindness and deafness (SCABD/SCAR3, MIM# 271250 and SCABD2). Eur J Hum Genet. 2016;24:1154–9. [PMC free article: PMC4970675] [PubMed: 26669662]
  • Guissart C, Li X, Leheup B, Drouot N, Montaut-Verient B, Raffo E, Jonveaux P, Roux AF, Claustres M, Fliegel L, Koenig M. Mutation of SLC9A1, encoding the major Na+/H+ exchanger, causes ataxia-deafness Lichtenstein-Knorr syndrome. Hum Mol Genet. 2015;24:463–70. [PubMed: 25205112]
  • Hamilton EM, Polder E, Vanderver A, Naidu S, Schiffmann R, Fisher K, Raguž AB, Blumkin L. H-ABC Research Group, van Berkel CG, Waisfisz Q, Simons C, Taft RJ, Abbink TE, Wolf NI, van der Knaap MS. Hypomyelination with atrophy of the basal ganglia and cerebellum: further delineation of the phenotype and genotype-phenotype correlation. Brain. 2014;137:1921–30. [PMC free article: PMC4345790] [PubMed: 24785942]
  • Hekman KE, Yu GY, Brown CD, Zhu H, Du X, Gervin K, Undlien DE, Peterson A, Stevanin G, Clark HB, Pulst SM, Bird TD, White KP, Gomez CM. A conserved eEF2 coding variant in SCA26 leads to loss of translational fidelity and increased susceptibility to proteostatic insult. Hum Mol Genet. 2012;21:5472–83. [PMC free article: PMC3516132] [PubMed: 23001565]
  • Hellenbroich Y, Bubel S, Pawlack H, Opitz S, Vieregge P, Schwinger E, Zühlke C. Refinement of the spinocerebellar ataxia type 4 locus in a large German family and exclusion of CAG repeat expansions in this region. J Neurol. 2003;250:668–71. [PubMed: 12796826]
  • Higgins JJ, Morton DH, Loveless JM. Posterior column ataxia with retinitis pigmentosa (AXPC1) maps to chromosome 1q31-q32. Neurology. 1999;52:146–50. [PubMed: 9921862]
  • Hills LB, Masri A, Konno K, Kakegawa W, Lam AT, Lim-Melia E, Chandy N, Hill RS, Partlow JN, Al-Saffar M, Nasir R, Stoler JM, Barkovich AJ, Watanabe M, Yuzaki M, Mochida GH. Deletions in GRID2 lead to a recessive syndrome of cerebellar ataxia and tonic upgaze in humans. Neurology. 2013;81:1378–86. [PMC free article: PMC3806907] [PubMed: 24078737]
  • Holzerova E, Danhauser K, Haack TB, Kremer LS, Melcher M, Ingold I, Kobayashi S, Terrile C, Wolf P, Schaper J, Mayatepek E, Baertling F, Friedmann Angeli JP, Conrad M, Strom TM, Meitinger T, Prokisch H, Distelmaier F. Human thioredoxin 2 deficiency impairs mitochondrial redox homeostasis and causes early-onset neurodegeneration. Brain. 2016;139:346–54. [PubMed: 26626369]
  • Ikeda Y, Dick KA, Weatherspoon MR, Gincel D, Armbrust KR, Dalton JC, Stevanin G, Durr A, Zuhlke C, Burk K, Clark HB, Brice A, Rothstein JD, Schut LJ, Day JW, Ranum LP. Spectrin mutations cause spinocerebellar ataxia type 5. Nat Genet. 2006;38:184–90. [PubMed: 16429157]
  • Ishiura H, Fukuda Y, Mitsui J, Nakahara Y, Ahsan B, Takahashi Y, Ichikawa Y, Goto J, Sakai T, Tsuji S. Posterior column ataxia with retinitis pigmentosa in a Japanese family with a novel mutation in FLVCR1. Neurogenetics. 2011;12:117–21. [PubMed: 21267618]
  • Jayadev S, Bird TD. Hereditary ataxias: overview. Genet Med. 2013;15:673–83. [PubMed: 23538602]
  • Jen JC, Graves TD, Hess EJ, Hanna MG, Griggs RC, Baloh RW., CINCH investigators. Primary episodic ataxias: diagnosis, pathogenesis and treatment. Brain. 2007;130:2484–93. [PubMed: 17575281]
  • Jiang H, Tang BS, Xu B, Zhao GH, Shen L, Tang JG, Li QH, Xia K. Frequency analysis of autosomal dominant spinocerebellar ataxias in mainland Chinese patients and clinical and molecular characterization of spinocerebellar ataxia type 6. Chin Med J (Engl). 2005;118:837–43. [PubMed: 15989765]
  • Jiang H, Wang J, Du, J, Duan R, Li J, Tang B. Progress in treating hereditary ataxia in mainland China. In: Sanders S, Zhang Z, Tang V, eds. Pathways to Cures: Neurodegenerative Diseases in China. Washington, DC: Science/AAAS; 2013:32-4.
  • Jinks RN, Puffenberger EG, Baple E, Harding B, Crino P, Fogo AB, Wenger O, Xin B, Koehler AE, McGlincy MH, Provencher MM, Smith JD, Tran L, Al Turki S, Chioza BA, Cross H, Harlalka GV, Hurles ME, Maroofian R, Heaps AD, Morton MC, Stempak L, Hildebrandt F, Sadowski CE, Zaritsky J, Campellone K, Morton DH, Wang H, Crosby A, Strauss KA. Recessive nephrocerebellar syndrome on the Galloway-Mowat syndrome spectrum is caused by homozygous protein-truncating mutations of WDR73. Brain. 2015;138:2173–90. [PMC free article: PMC4511861] [PubMed: 26070982]
  • Jobling RK, Assoum M, Gakh O, Blaser S, Raiman JA, Mignot C, Roze E, Dürr A, Brice A, Lévy N, Prasad C, Paton T, Paterson AD, Roslin NM, Marshall CR, Desvignes JP, Roëckel-Trevisiol N, Scherer SW, Rouleau GA, Mégarbané A, Isaya G, Delague V, Yoon G. PMPCA mutations cause abnormal mitochondrial protein processing in patients with non-progressive cerebellar ataxia. Brain. 2015;138:1505–17. [PMC free article: PMC4542620] [PubMed: 25808372]
  • Kawarai T, Tajima A, Kuroda Y, Saji N, Orlacchio A, Terasawa H, Shimizu H, Kita Y, Izumi Y, Mitsui T, Imoto I, Kaji R. A homozygous mutation of VWA3B causes cerebellar ataxia with intellectual disability. J Neurol Neurosurg Psychiatry. 2016;87:656–62. [PubMed: 26157035]
  • Kerber KA, Jen JC, Lee H, Nelson SF, Baloh RW. A new episodic ataxia syndrome with linkage to chromosome 19q13. Arch Neurol. 2007;64:749–52. [PubMed: 17502476]
  • Kim JY, Park SS, Joo SI, Kim JM, Jeon BS. Molecular analysis of Spinocerebellar ataxias in Koreans: frequencies and reference ranges of SCA1, SCA2, SCA3, SCA6, and SCA7. Mol Cells. 2001;12:336–41. [PubMed: 11804332]
  • Kim M, Sandford E, Gatica D, Qiu Y, Liu X, Zheng Y, Schulman BA, Xu J, Semple I, Ro SH, Kim B, Mavioglu RN, Tolun A, Jipa A, Takats S, Karpati M, Li JZ, Yapici Z, Juhasz G, Lee JH, Klionsky DJ, Burmeister M. Mutation in ATG5 reduces autophagy and leads to ataxia with developmental delay. Elife. 2016;5:e12245. pii. doi. [PMC free article: PMC4786408] [PubMed: 26812546] [CrossRef]
  • Klein CJ, Bird TD, Taner N, Lincoln S, Hjorth R, Wu Y, Kwok J, Mer G, Dyck PJ, Nicholson GA. DNMT1 amino acid 495 mutation and HSAN1E phenotype spectrum. Neurology. 2013;80:824–8. [PMC free article: PMC3598458] [PubMed: 23365052]
  • Klein CJ, Botuyan MV, Wu Y, Ward CJ, Nicholson GA, Hammans S, Hojo K, Yamanishi H, Karpf AR, Wallace DC, Simon M, Lander C, Boardman LA, Cunningham JM, Smith GE, Litchy WJ, Boes B, Atkinson EJ, Middha S. B Dyck PJ, Parisi JE, Mer G, Smith DI, Dyck PJ. Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss. Nat Genet. 2011;43:595–600. [PMC free article: PMC3102765] [PubMed: 21532572]
  • Krygier M, Kwarciany M, Wasilewska K, Pienkowski VM, Krawczyńska N, Zielonka D, Kosińska J, Stawinski P, Rudzińska-Bar M, Boczarska-Jedynak M, Karaszewski B, Limon J, Sławek J, Płoski R, Rydzanicz M. A study in a Polish ataxia cohort indicates genetic heterogeneity and points to MTCL1 as a novel candidate gene. Clin Genet. 2019;95:415–9. [PubMed: 30548255]
  • La Piana R, Cayami FK, Tran LT, Guerrero K, van Spaendonk R, Õunap K, Pajusalu S, Haack T, Wassmer E, Timmann D, Mierzewska H, Poll-Thé BT, Patel C, Cox H, Atik T, Onay H, Ozkınay F, Vanderver A, van der Knaap MS, Wolf NI, Bernard G. Diffuse hypomyelination is not obligate for POLR3-related disorders. Neurology. 2016;86:1622–6. [PMC free article: PMC4844237] [PubMed: 27029625]
  • La Spada AR. Trinucleotide repeat instability: genetic features and molecular mechanisms. Brain Pathol. 1997;7:943–63. [PMC free article: PMC8098141] [PubMed: 9217977]
  • Lagier-Tourenne C, Tazir M, López LC, Quinzii CM, Assoum M, Drouot N, Busso C, Makri S, Ali-Pacha L, Benhassine T, Anheim M, Lynch DR, Thibault C, Plewniak F, Bianchetti L, Tranchant C, Poch O, DiMauro S, Mandel JL, Barros MH, Hirano M, Koenig M. ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated with coenzyme Q10 deficiency. Am J Hum Genet. 2008;82:661–72. [PMC free article: PMC2427193] [PubMed: 18319074]
  • Leach EL, van Karnebeek CD, Townsend KN, Tarailo-Graovac M, Hukin J, Gibson WT. Episodic ataxia associated with a de novo SCN2A mutation. Eur J Paediatr Neurol. 2016;20:772–6. [PubMed: 27328862]
  • Lee YC, Durr A, Majczenko K, Huang YH, Liu YC, Lien CC, Tsai PC, Ichikawa Y, Goto J, Monin ML, Li JZ, Chung MY, Mundwiller E, Shakkottai V, Liu TT, Tesson C, Lu YC, Brice A, Tsuji S, Burmeister M, Stevanin G, Soong BW. Mutations in KCND3 cause spinocerebellar ataxia type 22. Ann Neurol. 2012;72:859–69. [PMC free article: PMC4085146] [PubMed: 23280837]
  • Leggo J, Dalton A, Morrison PJ, Dodge A, Connarty M, Kotze MJ, Rubinsztein DC. Analysis of spinocerebellar ataxia types 1, 2, 3, and 6, dentatorubral- pallidoluysian atrophy, and Friedreich's ataxia genes in spinocerebellar ataxia patients in the UK. J Med Genet. 1997;34:982–5. [PMC free article: PMC1051147] [PubMed: 9429138]
  • Lise S, Clarkson Y, Perkins E, Kwasniewska A, Sadighi Akha E, Schnekenberg RP, Suminaite D, Hope J, Baker I, Gregory L, Green A, Allan C, Lamble S, Jayawant S, Quaghebeur G, Cader MZ, Hughes S, Armstrong RJ, Kanapin A, Rimmer A, Lunter G, Mathieson I, Cazier JB, Buck D, Taylor JC, Bentley D, McVean G, Donnelly P, Knight SJ, Jackson M, Ragoussis J, Németh AH. Recessive mutations in SPTBN2 implicate β-III spectrin in both cognitive and motor development. PLoS Genet. 2012;8:e1003074. [PMC free article: PMC3516553] [PubMed: 23236289]
  • Mallaret M, Synofzik M, Lee J, Sagum CA, Mahajnah M, Sharkia R, Drouot N, Renaud M, Klein FA, Anheim M, Tranchant C, Mignot C, Mandel JL, Bedford M, Bauer P, Salih MA, Schüle R, Schöls L, Aldaz CM, Koenig M. The tumour suppressor gene WWOX is mutated in autosomal recessive cerebellar ataxia with epilepsy and mental retardation. Brain. 2014;137:411–9. [PMC free article: PMC3914474] [PubMed: 24369382]
  • Margolin DH, Kousi M, Chan YM, Lim ET, Schmahmann JD, Hadjivassiliou M, Hall JE, Adam I, Dwyer A, Plummer L, Aldrin SV, O'Rourke J, Kirby A, Lage K, Milunsky A, Milunsky JM, Chan J, Hedley-Whyte ET, Daly MJ, Katsanis N, Seminara SB. Ataxia, dementia, and hypogonadotropism caused by disordered ubiquitination. N Engl J Med. 2013;368:1992–2003. [PMC free article: PMC3738065] [PubMed: 23656588]
  • Maruyama H, Izumi Y, Morino H, Oda M, Toji H, Nakamura S, Kawakami H. Difference in disease-free survival curve and regional distribution according to subtype of spinocerebellar ataxia: a study of 1,286 Japanese patients. Am J Med Genet. 2002;114:578–83. [PubMed: 12116198]
  • Matsumura R, Futamura N, Ando N, Ueno S. Frequency of spinocerebellar ataxia mutations in the Kinki district of Japan. Acta Neurol Scand. 2003;107:38–41. [PubMed: 12542511]
  • Meijer IA, Hand CK, Grewal KK, Stefanelli MG, Ives EJ, Rouleau GA. A locus for autosomal dominant hereditary spastic ataxia, SAX1, maps to chromosome 12p13. Am J Hum Genet. 2002;70:763–9. [PMC free article: PMC384953] [PubMed: 11774073]
  • Merrill MJ, Nai D, Ghosh P, Edwards NA, Hallett M, Ray-Chaudhury A. Neuropathology in a case of episodic ataxia type 4. Neuropathol Appl Neurobiol. 2016;42:296–300. [PubMed: 26264377]
  • Miura S, Shibata H, Furuya H, Ohyagi Y, Osoegawa M, Miyoshi Y, Matsunaga H, Shibata A, Matsumoto N, Iwaki A, Taniwaki T, Kikuchi H, Kira J, Fukumaki Y. The contactin 4 gene locus at 3p26 is a candidate gene of SCA16. Neurology. 2006;67:1236–41. [PubMed: 17030759]
  • Miyatake S, Osaka H, Shiina M, Sasaki M, Takanashi J, Haginoya K, Wada T, Morimoto M, Ando N, Ikuta Y, Nakashima M, Tsurusaki Y, Miyake N, Ogata K, Matsumoto N, Saitsu H. Expanding the phenotypic spectrum of TUBB4A-associated hypomyelinating leukoencephalopathies. Neurology. 2014;82:2230–7. [PubMed: 24850488]
  • Miyoshi Y, Yamada T, Tanimura M, Taniwaki T, Arakawa K, Ohyagi Y, Furuya H, Yamamoto K, Sakai K, Sasazuki T, Kira J. A novel autosomal dominant spinocerebellar ataxia (SCA16) linked to chromosome 8q22.1-24.1. Neurology. 2001;57:96–100. [PubMed: 11445634]
  • Mollet J, Delahodde A, Serre V, Chretien D, Schlemmer D, Lombes A, Boddaert N, Desguerre I, de Lonlay P, de Baulny HO, Munnich A, Rötig A. CABC1 gene mutations cause ubiquinone deficiency with cerebellar ataxia and seizures. Am J Hum Genet. 2008;82:623–30. [PMC free article: PMC2427298] [PubMed: 18319072]
  • Moseley ML, Benzow KA, Schut LJ, Bird TD, Gomez CM, Barkhaus PE, Blindauer KA, Labuda M, Pandolfo M, Koob MD, Ranum LP. Incidence of dominant spinocerebellar and Friedreich triplet repeats among 361 ataxia families. Neurology. 1998;51:1666–71. [PubMed: 9855520]
  • Musselman KE, Stoyanov CT, Marasigan R, Jenkins ME, Konczak J, Morton SM, Bastian AJ. Prevalence of ataxia in children: A systematic review. Neurology. 2014;82:80–9. [PMC free article: PMC3873624] [PubMed: 24285620]
  • Muto V, Flex E, Kupchinsky Z, Primiano G, Galehdari H, Dehghani M, Cecchetti S, Carpentieri G, Rizza T, Mazaheri N, Sedaghat A, Vahidi Mehrjardi MY, Traversa A, Di Nottia M, Kousi MM, Jamshidi Y, Ciolfi A, Caputo V, Malamiri RA, Pantaleoni F, Martinelli S, Jeffries AR, Zeighami J, Sherafat A, Di Giuda D, Shariati GR, Carrozzo R, Katsanis N, Maroofian R, Servidei S, Tartaglia M. Biallelic SQSTM1 mutations in early-onset, variably progressive neurodegeneration. Neurology. 2018;91:e319–e330. [PMC free article: PMC6070386] [PubMed: 29959261]
  • Nagaoka U, Takashima M, Ishikawa K, Yoshizawa K, Yoshizawa T, Ishikawa M, Yamawaki T, Shoji S, Mizusawa H. A gene on SCA4 locus causes dominantly inherited pure cerebellar ataxia. Neurology. 2000;54:1971–5. [PubMed: 10822439]
  • Namavar Y, Barth PG, Poll-The BT, Baas F. Classification, diagnosis and potential mechanisms in pontocerebellar hypoplasia. Orphanet J Rare Dis. 2011;6:50. [PMC free article: PMC3159098] [PubMed: 21749694]
  • Nance MA. Clinical aspects of CAG repeat diseases. Brain Pathol. 1997;7:881–900. [PMC free article: PMC8098176] [PubMed: 9217974]
  • Németh AH, Kwasniewska AC, Lise S, Parolin Schnekenberg R, Becker EB, Bera KD, Shanks ME, Gregory L, Buck D, Zameel Cader M, Talbot K, de Silva R, Fletcher N, Hastings R, Jayawant S, Morrison PJ, Worth P, Taylor M, Tolmie J, O'Regan M., UK Ataxia Consortium. Valentine R, Packham E, Evans J, Seller A, Ragoussis J. Next generation sequencing for molecular diagnosis of neurological disorders using ataxias as a model. Brain. 2013 Oct;136(Pt 10):3106–18. [PMC free article: PMC3784284] [PubMed: 24030952]
  • Onat OE, Gulsuner S, Bilguvar K, Nazli Basak A, Topaloglu H, Tan M, Tan U, Gunel M, Ozcelik T. Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion. Eur J Hum Genet. 2013;21:281–5. [PMC free article: PMC3573203] [PubMed: 22892528]
  • Paulson HL. The spinocerebellar ataxias. J Neuroophthalmol. 2009;29:227–37. [PMC free article: PMC2739122] [PubMed: 19726947]
  • Pfeffer G, Blakely EL, Alston CL, Hassani A, Boggild M, Horvath R, Samuels DC, Taylor RW, Chinnery PF. Adult-onset spinocerebellar ataxia syndromes due to MTATP6 mutations. J Neurol Neurosurg Psychiatry. 2012;83:883–6. [PMC free article: PMC4034166] [PubMed: 22577227]
  • Pfeffer G, Pyle A, Griffin H, Miller J, Wilson V, Turnbull L, Fawcett K, Sims D, Eglon G, Hadjivassiliou M, Horvath R, Németh A, Chinnery PF. SPG7 mutations are a common cause of undiagnosed ataxia. Neurology. 2015;84:1174–6. [PMC free article: PMC4371411] [PubMed: 25681447]
  • Pierson TM, Adams D, Bonn F, Martinelli P, Cherukuri PF, Teer JK, Hansen NF, Cruz P. Mullikin For The Nisc Comparative Sequencing Program JC, Blakesley RW, Golas G, Kwan J, Sandler A, Fuentes Fajardo K, Markello T, Tifft C, Blackstone C, Rugarli EI, Langer T, Gahl WA, Toro C. Whole-exome sequencing identifies homozygous AFG3L2 mutations in a spastic ataxia-neuropathy syndrome linked to mitochondrial m-AAA proteases. PLoS Genet. 2011;7:e1002325. [PMC free article: PMC3192828] [PubMed: 22022284]
  • Ranum LP, Schut LJ, Lundgren JK, Orr HT, Livingston DM. Spinocerebellar ataxia type 5 in a family descended from the grandparents of President Lincoln maps to chromosome 11. Nat Genet. 1994;8:280–4. [PubMed: 7874171]
  • Renaud M, Anheim M, Kamsteeg EJ, Mallaret M, Mochel F, Vermeer S, Drouot N, Pouget J, Redin C, Salort-Campana E, Kremer HP, Verschuuren-Bemelmans CC, Muller J, Scheffer H, Durr A, Tranchant C, Koenig M. Autosomal recessive cerebellar ataxia type 3 due to ANO10 mutations: delineation and genotype-phenotype correlation study. JAMA Neurol. 2014;71:1305–10. [PubMed: 25089919]
  • Roxburgh RH, Marquis-Nicholson R, Ashton F, George AM, Lea RA, Eccles D, Mossman S, Bird T, van Gassen KL, Kamsteeg EJ, Love DR. The p.Ala510Val mutation in the SPG7 (paraplegin) gene is the most common mutation causing adult onset neurogenetic disease in patients of British ancestry. J Neurol. 2013;260:1286–94. [PubMed: 23269439]
  • Ruano L, Melo C, Silva MC, Coutinho P. The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology. 2014;42:174–83. [PubMed: 24603320]
  • Rüb U, Schöls L, Paulson H, Auburger G, Kermer P, Jen JC, Seidel K, Korf HW, Deller T. Clinical features, neurogenetics and neuropathology of the polyglutamine spinocerebellar ataxias type 1, 2, 3, 6 and 7. Prog Neurobiol. 2013;104:38–66. [PubMed: 23438480]
  • Sakai H, Yoshida K, Shimizu Y, Morita H, Ikeda S, Matsumoto N. Analysis of an insertion mutation in a cohort of 94 patients with spinocerebellar ataxia type 31 from Nagano, Japan. Neurogenetics. 2010;11:409–15. [PMC free article: PMC2944954] [PubMed: 20424877]
  • Saleem Q, Choudhry S, Mukerji M, Bashyam L, Padma MV, Chakravarthy A, Maheshwari MC, Jain S, Brahmachari SK. Molecular analysis of autosomal dominant hereditary ataxias in the Indian population: high frequency of SCA2 and evidence for a common founder mutation. Hum Genet. 2000;106:179–87. [PubMed: 10746559]
  • Sandford E, Burmeister M. Genes and genetic testing in hereditary ataxias. Genes (Basel). 2014;5:586–603. [PMC free article: PMC4198919] [PubMed: 25055202]
  • Santens P, Van Damme T, Steyaert W, Willaert A, Sablonnière B, De Paepe A, Coucke PJ, Dermaut B. RNF216 mutations as a novel cause of autosomal recessive Huntington-like disorder. Neurology. 2015;84:1760–6. [PubMed: 25841028]
  • Sato N, Amino T, Kobayashi K, Asakawa S, Ishiguro T, Tsunemi T, Takahashi M, Matsuura T, Flanigan KM, Iwasaki S, Ishino F, Saito Y, Murayama S, Yoshida M, Hashizume Y, Takahashi Y, Tsuji S, Shimizu N, Toda T, Ishikawa K, Mizusawa H. Spinocerebellar ataxia type 31 is associated with "inserted" penta-nucleotide repeats containing (TGGAA)n. Am J Hum Genet. 2009;85:544–57. [PMC free article: PMC2775824] [PubMed: 19878914]
  • Schelhaas HJ, Ippel PF, Hageman G, Sinke RJ, van der Laan EN, Beemer FA. Clinical and genetic analysis of a four-generation family with a distinct autosomal dominant cerebellar ataxia. J Neurol. 2001;248:113–20. [PubMed: 11284128]
  • Schelhaas HJ, Verbeek DS, Van de Warrenburg BP, Sinke RJ. SCA19 and SCA22: evidence for one locus with a worldwide distribution. Brain. 2004;127:E6. [PubMed: 14679032]
  • Scholl UI, Choi M, Liu T, Ramaekers VT, Häusler MG, Grimmer J, Tobe SW, Farhi A, Nelson-Williams C, Lifton RP. Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME syndrome) caused by mutations in KCNJ10. Proc Natl Acad Sci U S A. 2009;106:5842–7. [PMC free article: PMC2656559] [PubMed: 19289823]
  • Schöls L, Amoiridis G, Buttner T, Przuntek H, Epplen JT, Riess O. Autosomal dominant cerebellar ataxia: phenotypic differences in genetically defined subtypes? Ann Neurol. 1997;42:924–32. [PubMed: 9403486]
  • Schöls L, Bauer P, Schmidt T, Schulte T, Riess O. Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis. Lancet Neurol. 2004;3:291–304. [PubMed: 15099544]
  • Schwarz N, Hahn A, Bast T, Müller S, Löffler H, Maljevic S, Gaily E, Prehl I, Biskup S, Joensuu T, Lehesjoki AE, Neubauer BA, Lerche H, Hedrich UB. Mutations in the sodium channel gene SCN2A cause neonatal epilepsy with late-onset episodic ataxia. J Neurol. 2016;263:334–43. [PubMed: 26645390]
  • Seidel K, Siswanto S, Brunt ER, den Dunnen W, Korf HW, Rüb U. Brain pathology of spinocerebellar ataxias. Acta Neuropathol. 2012;124:1–21. [PubMed: 22684686]
  • Sellick GS, Barker KT, Stolte-Dijkstra I, Fleischmann C, Coleman RJ, Garrett C, Gloyn AL, Edghill EL, Hattersley AT, Wellauer PK, Goodwin G, Houlston RS. Mutations in PTF1A cause pancreatic and cerebellar agenesis. Nat Genet. 2004;36:1301–5. [PubMed: 15543146]
  • Seong E, Insolera R, Dulovic M, Kamsteeg EJ, Trinh J, Brüggemann N, Sandford E, Li S, Ozel AB, Li JZ, Jewett T, Kievit AJA, Münchau A, Shakkottai V, Klein C, Collins CA, Lohmann K, van de Warrenburg BP, Burmeister M. Mutations in VPS13D lead to a new recessive ataxia with spasticity and mitochondrial defects. Ann Neurol. 2018;83:1075–88. [PMC free article: PMC6105379] [PubMed: 29604224]
  • Serrano-Munuera C, Corral-Juan M, Stevanin G, San Nicolás H, Roig C, Corral J, Campos B, de Jorge L, Morcillo-Suárez C, Navarro A, Forlani S, Durr A, Kulisevsky J, Brice A, Sánchez I, Volpini V, Matilla-Dueñas A. New subtype of spinocerebellar ataxia with altered vertical eye movements mapping to chromosome 1p32. JAMA Neurol. 2013;70:764–71. [PubMed: 23700170]
  • Shadrina MI, Shulskaya MV, Klyushnikov SA, Nikopensius T, Nelis M, Kivistik PA, Komar AA, Limborska SA, Illarioshkin SN, Slominsky PA. ITPR1 gene p.Val1553Met mutation in Russian family with mild Spinocerebellar ataxia. Cerebellum Ataxias. 2016 Jan 13;3:2. [PMC free article: PMC4712497] [PubMed: 26770814]
  • Shakkottai VG, Fogel BL. Clinical neurogenetics: autosomal dominant spinocerebellar ataxia. Neurol Clin. 2013;31:987–1007. [PMC free article: PMC3818725] [PubMed: 24176420]
  • Shetty A, Gan-Or Z, Ashtiani S, Ruskey JA, van de Warrenburg B, Wassenberg T, Kamsteeg EJ, Rouleau GA, Suchowersky O. CAPN1 mutations: expanding the CAPN1-related phenotype: From hereditary spastic paraparesis to spastic ataxia. Eur J Med Genet. 2019;62:103605. [PubMed: 30572172]
  • Shi Y, Wang J, Li JD, Ren H, Guan W, He M, Yan W, Zhou Y, Hu Z, Zhang J, Xiao J, Su Z, Dai M, Wang J, Jiang H, Guo J, Zhou Y, Zhang F, Li N, Du J, Xu Q, Hu Y, Pan Q, Shen L, Wang G, Xia K, Zhang Z, Tang B. Identification of CHIP as a novel causative gene for autosomal recessive cerebellar ataxia. PLoS One. 2013;8:e81884. [PMC free article: PMC3846781] [PubMed: 24312598]
  • Shimizu Y, Yoshida K, Okano T, Ohara S, Hashimoto T, Fukushima Y, Ikeda S. Regional features of autosomal-dominant cerebellar ataxia in Nagano: clinical and molecular genetic analysis of 86 families. J Hum Genet. 2004;49:610–6. [PubMed: 15480876]
  • Siekierska A, Isrie M, Liu Y, Scheldeman C, Vanthillo N, Lagae L, de Witte PA, Van Esch H, Goldfarb M, Buyse GM. Gain-of-function FHF1 mutation causes early-onset epileptic encephalopathy with cerebellar atrophy. Neurology. 2016;86:2162–70. [PMC free article: PMC4898311] [PubMed: 27164707]
  • Silveira I, Miranda C, Guimaraes L, Moreira MC, Alonso I, Mendonca P, Ferro A, Pinto-Basto J, Coelho J, Ferreirinha F, Poirier J, Parreira E, Vale J, Januario C, Barbot C, Tuna A, Barros J, Koide R, Tsuji S, Holmes SE, Margolis RL, Jardim L, Pandolfo M, Coutinho P, Sequeiros J. Trinucleotide repeats in 202 families with ataxia: a small expanded (CAG)n allele at the SCA17 locus. Arch Neurol. 2002;59:623–9. [PubMed: 11939898]
  • Spiegel R, Pines O, Ta-Shma A, Burak E, Shaag A, Halvardson J, Edvardson S, Mahajna M, Zenvirt S, Saada A, Shalev S, Feuk L, Elpeleg O. Infantile cerebellar-retinal degeneration associated with a mutation in mitochondrial aconitase, ACO2. Am J Hum Genet. 2012;90:518–23. [PMC free article: PMC3309186] [PubMed: 22405087]
  • Steckley JL, Ebers GC, Cader MZ, McLachlan RS. An autosomal dominant disorder with episodic ataxia, vertigo, and tinnitus. Neurology. 2001;57:1499–502. [PubMed: 11673600]
  • Stevanin G, Bouslam N, Ravaux L, Boland A, Durr A, Brice A. Autosomal dominant cerebellar ataxia with sensory neuropathy maps to the spinocerebellar ataxia 25 (SCA25) locus on chromosome 2p15-p21. Am J Hum Genet. 2003;73 Suppl 1:2236.
  • Stevanin G, Herman A, Brice A, Durr A. Clinical and MRI findings in spinocerebellar ataxia type 5. Neurology. 1999;53:1355–7. [PubMed: 10522902]
  • Storey E, Bahlo M, Fahey M, Sisson O, Lueck CJ, Gardner RJ. A new dominantly inherited pure cerebellar ataxia, SCA 30. J Neurol Neurosurg Psychiatry. 2009;80:408–11. [PubMed: 18996908]
  • Storey E, du Sart D, Shaw JH, Lorentzos P, Kelly L, McKinley Gardner RJ, Forrest SM, Biros I, Nicholson GA. Frequency of spinocerebellar ataxia types 1, 2, 3, 6, and 7 in Australian patients with spinocerebellar ataxia. Am J Med Genet. 2000;95:351–7. [PubMed: 11186889]
  • Sun Y, Almomani R, Breedveld GJ, Santen GW, Aten E, Lefeber DJ, Hoff JI, Brusse E, Verheijen FW, Verdijk RM, Kriek M, Oostra B, Breuning MH, Losekoot M, den Dunnen JT, van de Warrenburg BP, Maat-Kievit AJ. Autosomal recessive spinocerebellar ataxia 7 (SCAR7) is caused by variants in TPP1, the gene involved in classic late-infantile neuronal ceroid lipofuscinosis 2 disease (CLN2 disease). Hum Mutat. 2013;34:706–13. [PubMed: 23418007]
  • Sun YM, Lu C, Wu ZY. Spinocerebellar ataxia: relationship between phenotype and genotype - a review. Clin Genet. 2016;90:305–14. [PubMed: 27220866]
  • Svenstrup K, Nielsen TT, Aidt F, Rostgaard N, Duno M, Wibrand F, Vinther-Jensen T, Law I, Vissing J, Roos P, Hjermind LE, Nielsen JE. SCA28: Novel mutation in the AFG3L2 proteolytic domain causes a mild cerebellar syndrome with selective type-1 muscle fiber atrophy. Cerebellum. 2017;16:62–7. [PubMed: 26868664]
  • Sweadner KJ, Toro C, Whitlow CT, Snively BM, Cook JF, Ozelius LJ, Markello TC, Brashear A. ATP1A3 Mutation in Adult Rapid-Onset Ataxia. PLoS One. 2016;11:e0151429. [PMC free article: PMC4798776] [PubMed: 26990090]
  • Synofzik M, Schüle R, Schulze M, Gburek-Augustat J, Schweizer R, Schirmacher A, Krägeloh-Mann I, Gonzalez M, Young P, Züchner S, Schöls L, Bauer P. Phenotype and frequency of STUB1 mutations: next-generation screenings in Caucasian ataxia and spastic paraplegia cohorts. Orphanet J Rare Dis. 2014;9:57. [PMC free article: PMC4021831] [PubMed: 24742043]
  • Synofzik M, Smets K, Mallaret M, Di Bella D, Gallenmüller C, Baets J, Schulze M, Magri S, Sarto E, Mustafa M, Deconinck T, Haack T, Züchner S, Gonzalez M, Timmann D, Stendel C, Klopstock T, Durr A, Tranchant C, Sturm M, Hamza W, Nanetti L, Mariotti C, Koenig M, Schöls L, Schüle R, de Jonghe P, Anheim M, Taroni F, Bauer P. SYNE1 ataxia is a common recessive ataxia with major non-cerebellar features: a large multi-centre study. Brain. 2016;139:1378–93. [PMC free article: PMC6363274] [PubMed: 27086870]
  • Tang B, Liu C, Shen L, Dai H, Pan Q, Jing L, Ouyang S, Xia J. Frequency of SCA1, SCA2, SCA3/MJD, SCA6, SCA7, and DRPLA CAG trinucleotide repeat expansion in patients with hereditary spinocerebellar ataxia from Chinese kindreds. Arch Neurol. 2000;57:540–4. [PubMed: 10768629]
  • Thomas AC, Williams H, Setó-Salvia N, Bacchelli C, Jenkins D, O'Sullivan M, Mengrelis K, Ishida M, Ocaka L, Chanudet E, James C, Lescai F, Anderson G, Morrogh D, Ryten M, Duncan AJ, Pai YJ, Saraiva JM, Ramos F, Farren B, Saunders D, Vernay B, Gissen P, Straatmaan-Iwanowska A, Baas F, Wood NW, Hersheson J, Houlden H, Hurst J, Scott R, Bitner-Glindzicz M, Moore GE, Sousa SB, Stanier P. Mutations in SNX14 cause a distinctive autosomal-recessive cerebellar ataxia and intellectual disability syndrome. Am J Hum Genet. 2014;95:611–21. [PMC free article: PMC4225633] [PubMed: 25439728]
  • Tsoi H, Yu AC, Chen ZS, Ng NK, Chan AY, Yuen LY, Abrigo JM, Tsang SY, Tsui SK, Tong TM, Lo IF, Lam ST, Mok VC, Wong LK, Ngo JC, Lau KF, Chan TF, Chan HY. A novel missense mutation in CCDC88C activates the JNK pathway and causes a dominant form of spinocerebellar ataxia. J Med Genet. 2014;51:590–5. [PMC free article: PMC4145425] [PubMed: 25062847]
  • van de Warrenburg BP, Sinke RJ, Verschuuren-Bemelmans CC, Scheffer H, Brunt ER, Ippel PF, Maat-Kievit JA, Dooijes D, Notermans NC, Lindhout D, Knoers NV, Kremer HP. Spinocerebellar ataxias in the Netherlands: prevalence and age at onset variance analysis. Neurology. 2002;58:702–8. [PubMed: 11889231]
  • van Gassen KL, van der Heijden CD, de Bot ST, den Dunnen WF, van den Berg LH, Verschuuren-Bemelmans CC, Kremer HP, Veldink JH, Kamsteeg EJ, Scheffer H, van de Warrenburg BP. Genotype-phenotype correlations in spastic paraplegia type 7: a study in a large Dutch cohort. Brain. 2012;135:2994–3004. [PubMed: 22964162]
  • Van Schil K, Meire F, Karlstetter M, Bauwens M, Verdin H, Coppieters F, Scheiffert E, Van Nechel C, Langmann T, Deconinck N, De Baere E. Early-onset autosomal recessive cerebellar ataxia associated with retinal dystrophy: new human hotfoot phenotype caused by homozygous GRID2 deletion. Genet Med. 2015;17:291–9. [PubMed: 25122145]
  • van Swieten JC, Brusse E, de Graaf BM, Krieger E, van de Graaf R, de Koning I, Maat-Kievit A, Leegwater P, Dooijes D, Oostra BA, Heutink P. A mutation in the fibroblast growth factor 14 gene is associated with autosomal dominant cerebral ataxia. Am J Hum Genet. 2003;72:191–9. [PMC free article: PMC378625] [PubMed: 12489043]
  • Verbeek DS, Schelhaas JH, Ippel EF, Beemer FA, Pearson PL, Sinke RJ. Identification of a novel SCA locus (SCA19) in a Dutch autosomal dominant cerebellar ataxia family on chromosome region 1p21-q21. Hum Genet. 2002;111:388–93. [PubMed: 12384780]
  • Verbeek DS, van de Warrenburg BP, Wesseling P, Pearson PL, Kremer HP, Sinke RJ. Mapping of the SCA23 locus involved in autosomal dominant cerebellar ataxia to chromosome region 20p13-12.3. Brain. 2004;127:2551–7. [PubMed: 15306549]
  • Vermeer S, Hoischen A, Meijer RP, Gilissen C, Neveling K, Wieskamp N, de Brouwer A, Koenig M, Anheim M, Assoum M, Drouot N, Todorovic S, Milic-Rasic V, Lochmüller H, Stevanin G, Goizet C, David A, Durr A, Brice A, Kremer B, van de Warrenburg BP, Schijvenaars MM, Heister A, Kwint M, Arts P, van der Wijst J, Veltman J, Kamsteeg EJ, Scheffer H, Knoers N. Targeted next-generation sequencing of a 12.5 Mb homozygous region reveals ANO10 mutations in patients with autosomal-recessive cerebellar ataxia. Am J Hum Genet. 2010;87:813–9. [PMC free article: PMC2997370] [PubMed: 21092923]
  • Vineeth VS, Das Bhowmik A, Balakrishnan S, Dalal A, Aggarwal S. Homozygous PCDH12 variants result in phenotype of cerebellar ataxia, dystonia, retinopathy, and dysmorphism. J Hum Genet. 2019;64:183–9. [PubMed: 30459466]
  • Vuillaume I, Devos D, Schraen-Maschke S, Dina C, Lemainque A, Vasseur F, Bocquillon G, Devos P, Kocinski C, Marzys C, Destee A, Sablonniere B. A new locus for spinocerebellar ataxia (SCA21) maps to chromosome 7p21.3-p15.1. Ann Neurol. 2002;52:666–70. [PubMed: 12402269]
  • Wan J, Steffen J, Yourshaw M, Mamsa H, Andersen E, Rudnik-Schöneborn S, Pope K, Howell KB, McLean CA, Kornberg AJ, Joseph J, Lockhart PJ, Zerres K, Ryan MM, Nelson SF, Koehler CM, Jen JC. Loss of function of SLC25A46 causes lethal congenital pontocerebellar hypoplasia. Brain. 2016;139:2877–90. [PMC free article: PMC5840878] [PubMed: 27543974]
  • Wang JL, Yang X, Xia K, Hu ZM, Weng L, Jin X, Jiang H, Zhang P, Shen L, Guo JF, Li N, Li YR, Lei LF, Zhou J, Du J, Zhou YF, Pan Q, Wang J, Wang J, Li RQ, Tang BS. TGM6 identified as a novel causative gene of spinocerebellar ataxias using exome sequencing. Brain. 2010;133:3510–8. [PubMed: 21106500]
  • Watanabe H, Tanaka F, Matsumoto M, Doyu M, Ando T, Mitsuma T, Sobue G. Frequency analysis of autosomal dominant cerebellar ataxias in Japanese patients and clinical characterization of spinocerebellar ataxia type 6. Clin Genet. 1998;53:13–9. [PubMed: 9550356]
  • Winter N, Kovermann P, Fahlke C. A point mutation associated with episodic ataxia 6 increases glutamate transporter anion currents. Brain. 2012;135:3416–25. [PubMed: 23107647]
  • Yapici Z, Eraksoy M. Non-progressive congenital ataxia with cerebellar hypoplasia in three families. Acta Paediatr. 2005;94:248–53. [PubMed: 15981765]
  • Yu GY, Howell MJ, Roller MJ, Xie TD, Gomez CM. Spinocerebellar ataxia type 26 maps to chromosome 19p13.3 adjacent to SCA6. Ann Neurol. 2005;57:349–54. [PubMed: 15732118]
  • Zanni G, Bertini E, Bellcross C, Nedelec B, Froyen G, Neuhäuser G, Opitz JM, Chelly J. X-linked congenital ataxia: a new locus maps to Xq25-q27.1. Am J Med Genet A. 2008;146A:593–600. [PubMed: 18241076]
  • Zanni G, Bertini ES. X-linked disorders with cerebellar dysgenesis. Orphanet J Rare Dis. 2011;6:24. [PMC free article: PMC3115841] [PubMed: 21569638]
  • Zanni G, Calì T, Kalscheuer VM, Ottolini D, Barresi S, Lebrun N, Montecchi-Palazzi L, Hu H, Chelly J, Bertini E, Brini M, Carafoli E. Mutation of plasma membrane Ca2+ ATPase isoform 3 in a family with X-linked congenital cerebellar ataxia impairs Ca2+ homeostasis. Proc Natl Acad Sci U S A. 2012;2012;109:14514–9. [PMC free article: PMC3437887] [PubMed: 22912398]
  • Zanni G, Saillour Y, Nagara M, Billuart P, Castelnau L, Moraine C, Faivre L, Bertini E, Durr A, Guichet A, Rodriguez D, des Portes V, Beldjord C, Chelly J. Oligophrenin 1 mutations frequently cause X-linked mental retardation with cerebellar hypoplasia. Neurology. 2005;65:1364–9. [PubMed: 16221952]
  • Zortea M, Armani M, Pastorello E, Nunez GF, Lombardi S, Tonello S, Rigoni MT, Zuliani L, Mostacciuolo ML, Gellera C, Di Donato S, Trevisan CP. Prevalence of inherited ataxias in the province of Padua, Italy. Neuroepidemiology. 2004;23:275–80. [PubMed: 15297793]

Chapter Notes

Revision History

  • 25 July 2019 (tb) Revision: Addition of TRPC3, MME, GRM1, FAT2, PLD3, PUM1, STUB1, and associated references
  • 18 April 2019 (tb) Revision: Addition of RFC1, CAPN1, MTCL1, PCDH12, SNX14, and associated references
  • 27 September 2018 (tb) Revision: TDP2 added to Table 3
  • 23 August 2018 (tb) Revision: genes added to Table 3: GDAP2, VPS13D, SQSTM1
  • 3 November 2016 (tb) Revision: addition of FGF12, ATP1A3, POLR3A, POLR3B, SLC25A46, TSFM, VWA3B, WDR73, ATP2B3, and citations
  • 3 March 2016 (tb) Revision: addition of CACNA1G, C9orf72, SCN2A, ATG5, PMPCA, TXN2, UBA5, and citations
  • 11 June 2015 (tb/aa) Revision: addition of SNX4 (SCAR20), RNF216 (Gordon Holmes syndrome), and citations
  • 2 April 2015 (tb) Revision: mutation of PNKP added as a cause of AR ataxia; ITPR1 added as the gene associated with SCA16
  • 5 March 2015 (tb) Revision: addition of SPG7 – Table 5
  • 26 November 2014 (tb) Revision: addition of PNPLA6, CLN5, and CWF19L1
  • 30 October 2014 (tb) Revision: addition of Brown-Vialetto-Van Laere syndrome 2 (caused by mutation of SLC52A2) and Wolfram syndrome (caused by mutation of WFS1)
  • 16 October 2014 (aa) Revision: addition of SCA40, caused by mutation of CCDC88C
  • 2 October 2014 (tb) Revision: SCA21, Lichtenstein-Knorr Syndrome added
  • 28 August 2014 (tb) Revision: addition of ELOVL5 and LAMA
  • 14 August 2014 (me) Comprehensive update posted live
  • 3 April 2014 (tb) Revision: to information on KIAA0226 [Assoum et al 2013]
  • 20 March 2014 (tb) Revision: SCA34; SPTBN2 associated with autosomal recessive cerebellar ataxia; update in prevalence information
  • 27 February 2014 (tb) Revision: addition of CLCN2, WWOX, and links to OMIM Phenotypic Series
  • 13 February 2014 (tb) Revision: review of spastic ataxia
  • 23 January 2014 (tb) Revision: edits to prevalence, clinical features of ADCA, AR single cases; added SCA37 to Tables 1&2; added SCA32 and SCA34 to Table 1.
  • 7 November 2013 (tb) Revision: autosomal recessive SCA with eye movement abnormalities (most notably tonic upgaze) caused by mutations in GRID2
  • 17 January 2013 (tb) Revision: mutation in KCND3 found to cause SCA19 and SCA22 (SCA19/22)
  • 3 January 2013 (tb) Revision: clinical testing available for SCA35
  • 1 November 2012 (tb) Revision: mutations in EEF2 identified as causative for SCA26
  • 11 October 2012 (tb) Revision: mutations in VAMP1 identified as causative for SPAX1; mutations in GRM1 identified as causative for ARCA
  • 13 September 2012 (tb) Revision: addition of Onat et al [2013]
  • 31 May 2012 (tb) Revision: to include Pfeffer et al 2012 re: ataxia associated with missense mutations in MTATP6; SCA18 assigned by OMIM to ataxia phenotype described by Brkanac et al 2002 and 2009.
  • 26 April 2012 (tb) Revision: autosomal recessive SCA caused by mutation in ANO10 added
  • 16 February 2012 (tb) Revision: SCA35 added
  • 26 January 2012 (tb) Revision: updated information on SCA with axonal neuropathy; SCAR9 added
  • 15 September 2011 (tb) Revision: additional rare form of autosomal recessive ataxia
  • 21 July 2011 (tb) Revision: addition of SCA36
  • 17 February 2011 (me) Comprehensive update posted live
  • 6 January 2009 (cd) Revision: 260-kb duplication of 11q12.2-11q12.3 identified as probable cause of SCA20
  • 25 September 2008 (tb) Revision: heterozygous mutations in AFG3L2 identified as the cause of SCA28
  • 27 February 2008 (tb) Revision: deletion of part of ITPR1 identified as cause of SCA15
  • 18 December 2007 (tb) Revision: mutations in TTBK2 associated with SCA11
  • 27 June 2007 (me) Comprehensive update posted live
  • 27 October 2006 (tb) Revision: SCA16 reassigned to 3p26.2-pter
  • 31 August 2006 (tb) Revision: clinical testing available for infantile-onset spinocerebellar ataxia (IOSCA)
  • 4 August 2006 (tb) Revision: clinical testing available for SCA5, SCA13, SCA27, and 16q22-linked SCA
  • 27 April 2006 (tb) Revision: mutations in KCNC3 cause SCA13; additions to Causes- Autosomal Dominant Cerebellar Ataxias, References
  • 1 February 2006 (tb) Revision: mutations in SPTBN2 cause SCA5
  • 19 December 2005 (tb) Revision: Marinesco-Sjögren caused by mutations in SIL1
  • 8 November 2005 (tb) Revision: SCA28
  • 17 October 2005 (tb) Revision: SCA27
  • 14 September 2005 (tb) Revision: author changes
  • 12 July 2005 (tb) Revision: SCA4 gene and protein identified
  • 4 April 2005 (tb) Revision: SCA26 added
  • 8 February 2005 (me) Comprehensive update posted live
  • 23 November 2004 (tb) Revision: author changes
  • 14 October 2004 (tb/cd) Revision
  • 30 June 2004 (tb) Revision: SCA20 added
  • 11 June 2004 (tb) Revision: SCA12 gene identified
  • 27 May 2004 (ca) Revision: addition of SCA world map (Figure 1)
  • 23 January 2004 (tb) Revision: SCA19
  • 30 December 2003 (tb) Revision: change in test availability
  • 2 October 2003 (tb) Revision: X-linked sideroblastic anemia gene identified
  • 17 July 2003 (tb) Revision: SCA22
  • 20 May 2003 (tb) Revision
  • 27 February 2003 (me) Comprehensive update posted live
  • 9 January 2002 (tb) Revision: SCA18
  • 8 November 2001 (tb) Revision: SCA15, SCA18
  • 14 August 2001 (tb) Revision: SCA17
  • 25 July 2001 (tb) Revision: SCA16
  • 11 April 2001 (tb) Revision: SCA12
  • 8 December 2000 (tb) Revision: SCA10
  • 15 November 2000 (tb) Revision: AOA
  • 8 November 2000 (tb) Revision: SCA10
  • 25 September 2000 (tb) Revision: SCA8
  • 25 August 2000 (tb) Revision: SCA14
  • 7 August 2000 (tb) Revision: Hereditary Ataxias/Clinical Features & References
  • 14 June 2000 (tb) Revision
  • 22 May 2000 (tb) Revision
  • 14 January 2000 (tb) Revision
  • 25 October 1999 (tb) Revision
  • 31 August 1999 (tb) Revision
  • 11 March 1999 (tb) Revision: SCA8
  • 5 March 1999 (tb) Revision: SCA10
  • 28 October 1998 (me) Overview posted live
  • 23 June 1998 (tb) Original submission
Copyright © 1993-2021, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source ( and copyright (© 1993-2021 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

Bookshelf ID: NBK1138PMID: 20301317


Related information

  • PMC
    PubMed Central citations
  • PubMed
    Links to PubMed

Similar articles in PubMed

See reviews...See all...

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...