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Adam MP, Everman DB, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022.

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Hereditary Ataxia Overview

, MD.

Author Information

Initial Posting: ; Last Update: June 16, 2022.

Estimated reading time: 23 minutes

Summary

The purpose of this overview on hereditary ataxia is to increase the awareness of clinicians regarding the causes of hereditary ataxia, related genetic counseling issues, and management.

Goal 1.

Briefly describe the clinical characteristics of hereditary ataxias (sometimes referred to as "primary hereditary ataxias") for which an adult with ataxia or the caregivers of a child with ataxia would seek diagnosis and management from a neurologist as part of a multidisciplinary team.

Goal 2.

Review common and notable genetic causes of hereditary ataxia.

Goal 3.

Provide an evaluation strategy to identify the genetic cause of hereditary ataxia in a proband.

Goal 4.

Inform genetic counseling of family members of an individual with hereditary ataxia.

Goal 5.

Review management of hereditary ataxia.

1. Clinical Characteristics of Primary Hereditary Ataxia

For the purposes of this chapter, which deals exclusively with hereditary ataxias, the term "primary hereditary ataxia" has been used to designate hereditary ataxias for which an adult with ataxia or the caregivers of a child with ataxia would seek diagnosis and management from a neurologist as part of a multidisciplinary team.

Use of the term "primary hereditary ataxia" is intended to exclude hereditary multisystem disorders in which ataxia may be observed, but is usually not the primary presenting manifestation.

Excluded Categories

For the purposes of this overview the following categories of hereditary disorders in which ataxia may occur are not considered primary hereditary ataxias:

Manifestations

The manifestations of many of the more common primary hereditary ataxias discussed in Section 2 of this overview become evident between ages 30 and 50 years, although manifestations of other ataxias are evident before age 25 years (e.g., ataxia with oculomotor apraxia, Friedreich ataxia) or before age five years (e.g., ataxia-telangiectasia).

The first manifestation of ataxia can include:

  • Most commonly, a slowly progressive gait disorder that appears unsteady and predisposes to unexpected falls;
  • Disequilibrium ("dizziness"), which may lead to an evaluation for peripheral vestibular dysfunction;
  • Hand and finger clumsiness or tremor, which may raise the possibility of essential tremor or even parkinsonism;
  • Slurring of speech or unexpected choking, which could lead to an evaluation for amyotrophic lateral sclerosis (ALS);
  • Rarely, double vision, which could lead to an evaluation by an optometrist or ophthalmologist.

At disease onset, these manifestations may be intermittent or evident only at certain times (e.g., later in the day, when tired, after consuming alcohol). The manifestations typically become constant and slowly worsen.

Typical cerebellar features on neurologic examination include:

  • Wide-based, staggering walk with difficulty performing tandem gait;
  • Truncal instability when sitting unsupported;
  • Difficulty with target maneuvers of the upper extremities (dysmetria, terminal tremor);
  • Slowed rapid alternating movements (dysdiadochokinesis);
  • Dysarthria (slowed or slurred articulation, variable pitch and loudness, monotonous or "scanning" speech);
  • Abnormal eye movements (saccade intrusions in primary gaze, nystagmus in horizontal or vertical gaze, saccade hypermetria).

Non-cerebellar findings that can mimic or exacerbate the cerebellar ataxia (which can be identified by examination or testing) include:

  • Alterations in descending frontal or parietal motor pathways (e.g., in normal pressure hydrocephalus);
  • Brain stem changes that disrupt cerebellar pathways (e.g., in central vestibular dysfunction);
  • Sensory pathway dysfunctions that alter input to the cerebellum (visual, peripheral vestibular, posterior column, peripheral sensory);
  • Other sources of motor change, especially as they affect gait (weakness, rigidity, spasticity);
  • Non-neurologic disorders (e.g., joint disease).

Brain imaging (MRI, MRS, PET) confirms the presence of cerebellar atrophy or hypoplasia.

Electronystagmography can document dysfunction in cerebellar, vestibular, or oculomotor pathways.

Progression of a hereditary ataxia usually leads to:

  • Use of assistive devices for ambulation five to ten years after onset and ultimately to wheelchair dependence;
  • Choking or falls resulting in, for example, head injury or hip fracture, which are common causes of morbidity and mortality;
  • Infection and sepsis (from aspiration or other pneumonia, urinary tract infection, decubiti), especially prominent in the later stages of disease;
  • Decline in self-care ability, increasing risk of falls, dependence on a feeding tube, and/or incontinence;
  • The family or caregiver's need to consider more in-home care assistance or out-of-home placement.

Affected individuals do not usually live longer than 25 years after manifestations emerge.

See Figure 1 for worldwide distribution of the most common primary hereditary ataxias.

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 (more...)

2. Causes of Hereditary Ataxia

Note: Up to 40% of adults with late-onset cerebellar ataxia and no family history of ataxia will not have an identified genetic cause despite a comprehensive evaluation (see Section 3).

The causes of primary hereditary ataxia included in this overview are separated into nucleotide repeat disorders (Table 1 and Table 2), other common hereditary ataxias (Table 3), and potentially treatable causes of hereditary ataxia (Table 4 and Table 5).

Nucleotide Repeat Disorders

The nucleotide repeat disorders (see Table 1), the most common cause of hereditary ataxia, are discussed separately because of their unique molecular mechanism and inheritance issues.

Molecular Mechanism

In nucleotide repeat disorders, a sequence of nucleotides is repeated a number of times in tandem within a gene (in an exon or intron) or near a gene. For a given gene, the size of the nucleotide repeats varies: smaller numbers of repeats are common and not associated with phenotypic abnormalities, whereas abnormally large numbers of repeats (uninterrupted or interrupted) may be associated with phenotypic abnormalities.

Inheritance Issues

All three modes of inheritance can be observed in nucleotide repeat disorders: autosomal dominant, autosomal recessive, and X-linked.

Autosomal dominant inheritance. A unique aspect of autosomal dominant inheritance of nucleotide repeat disorders is anticipation, the earlier onset and increasing severity of disease in subsequent generations as a result of expansion in the repeat size during transmission. In some disorders, anticipation may be so extreme that children with early-onset, severe, and usually phenotypically different disease die of disease complications long before the affected parent or grandparent is symptomatic.

X-linked inheritance. A unique aspect of fragile X tremor/ataxia syndrome, the most common X-linked ataxia, is its occurrence in males and females with repeat sizes in the premutation range (see Table 2).

Table 1.

Hereditary Ataxias Caused by Nucleotide Repeat Expansions: Clinical Findings

Gene 1Disorder 2MOIDistinguishing Non-Ataxic Clinical FeaturesComment
Most commonly involved genes 3
ATN1 DRPLA ADChorea, dementia, myoclonus, seizures; mimics Huntington disease.
  • Anticipation is prominent.
  • More common in Japan
ATXN1 SCA1 ADPeripheral neuropathy, pyramidal signs; early bulbar features; occasional cognitive declineAnticipation is more likely w/paternal transmission.
ATXN2 SCA2 AD↓ DTRs, dementia, peripheral neuropathy, slow saccadic eye movements
  • Anticipation is more likely w/paternal transmission.
  • Large Cuban founder population
ATXN3 SCA3 ADAmyotrophy, fasciculations, sensory loss; lid retraction, nystagmus, & ↓ saccade velocity; pyramidal & extrapyramidal signs; shortened life span
  • Anticipation may be more likely w/paternal transmission.
  • Large Portuguese founder population
  • Also known as Machado-Joseph disease
ATXN7 SCA7 ADVisual loss w/retinopathy; often rapidly progressive; shortened life spanAnticipation is prominent w/more marked repeat expansions w/paternal transmission.
ATXN8 SCA8 ADSlowly progressive, sometimes brisk DTRs, ↓ vibration sense; rarely, cognitive impairment in persons w/earlier onsetAnticipation is more likely w/maternal transmission.
ATXN8OS
ATXN10 SCA10 ADSeizures in certain families
  • Anticipation can occur w/paternal transmission.
  • Large Mexican founder population
CACNA1A SCA6 ADMay begin w/episodic ataxia, very slow progression; onset often after age 50 yrs; normal life span
  • Anticipation is not seen.
  • See Table 3 for ataxia caused by missense variants.
FXN Friedreich ataxia ARGenerally childhood onset w/slowly progressive ataxia, absent tendon reflexes, Babinski responses, posterior column sensory loss, cardiomyopathy, scoliosis, pes cavus, & diabetes; in some: onset ≥25 yrs, slower progression, & retained reflexesAnticipation is not seen.
RFC1 RFC1 CANVAS / spectrum disorder ARSpectrum ranges from typical cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS), to cerebellar, sensory, & vestibular impairment, to more limited phenotypes involving predominantly or exclusively 1 of the systems involved in balance control.Anticipation is not seen.
TBP SCA17 ADMental deterioration; occasional chorea, dystonia, myoclonus, epilepsyAnticipation is infrequently observed.
Less commonly involved genes
BEAN1 3, 4SCA31 (OMIM 117210)ADNormal sensationCommon in Japan
FMR1 Fragile X-associated tremor/ataxia syndrome (FXTAS) (See FMR1 Disorders.)XL
  • Anticipation occurs almost exclusively w/maternal transmission.
  • Most common X-linked ataxia; occurs in male & female premutation carriers
NOP56 3, 4 SCA36 ADHyperreflexia, muscle fasciculations, tongue atrophyInsufficient evidence for anticipation
PPP2R2B 3, 4SCA12 (OMIM 604326)ADAction tremor in the 4th decade, cognitive/psychiatric disorders incl dementia, hyperreflexia, slowly progressive ataxia, subtle parkinsonism possibleInsufficient evidence for anticipation

DRPLA = dentatorubral-pallidoluysian atrophy; DTR = deep tendon reflex; SCA = spinocerebellar ataxia

1.

Genes are listed in alphabetic order within prevalence categories.

2.

For more information see hyperlinked GeneReview. An OMIM phenotype entry is provided if a GeneReview is not available.

3.
4.

Nucleotide repeat expansions in BEAN1, NOP56, and PPP2R2B represent relatively rare causes of hereditary ataxia.

Table 2.

Hereditary Ataxias Caused by Nucleotide Repeat Expansions: Molecular Genetics

Gene 1% of Pathogenic VariantsNucleotide Repeat (Amino Acid)Repeat LocationNormal Repeat NumberFull-Penetrance Pathogenic Repeat NumberComment
ATN1 100CAG (Gln)Exon 56-35≥48
ATXN1 100CAG (Gln)Exon 86-35≥39
ATXN2 100CAG (Gln)Exon 1≤31≥33
ATXN3 100CAG (Gln)Exon 812-4460-87
ATXN7 100CAG (Gln)Exon 14-19≥36
ATXN8 100CAG (Gln)Exon 1~80Unknown
ATXN8OS 100CTG3' UTR15-50 CTA/CTG≥71-1300 CTA/CTG 2Penetrance is <100%. 2
ATXN10 100ATTCTIntron 910-32≥800Repeat interruptions are assoc w/presence of seizures.
BEAN1 100TGGAAIntron 602.5- to 3.8-kb insertion
CACNA1A 3>99CAG (Gln)Exon 7≤1820-33See Table 3 for phenotype assoc w/variants that are not nucleotide repeat disorders.
FMR1 >99CGG5' UTR5-44≥200Premutation alleles: 55-200 CGG repeats
FXN ~98GAAIntron 15-33≥66In about 5% of affected persons 1 FXN allele is an expanded GAA repeat & 1 is a pathogenic missense variant.
NOP56 100GGCCTGIntron 13-14≥650
PPP2R2B 100CAGPromoter7-3151-78
RFC1 100AAGGG 4Intron 2Unknown~400-~2000ACAGG repeat expansion has been reported in 3 persons from Asian & Asian Pacific populations. 4
TBP 100CAG or CAA (Gln)Exon 325-40≥49
1.

Genes are listed in alphabetic order.

2.

While penetrance less than 100% has been reported at all repeat sizes, higher penetrance is reported for CTA/CTG repeat sizes of 80-250 [Ranum et al 1999].

3.

The majority of CACNA1A pathogenic variants are CAG repeat expansions associated with spinocerebellar ataxia type 6. Heterozygous CACNA1A missense, nonsense, splice site, frameshift, and exon/multiexon deletions have been reported in individuals with episodic ataxia type 2 and progressive cerebellar ataxia.

4.

RFC1 intron 2 contains a microsatellite region with variable benign AAAAG repeats (range: 11-200 repeats) and/or benign AAAGG repeats (range: 40-1000 repeats). Interruption of the benign AAAAG/AAAGG repeated units with biallelic pathogenic AAGGG expansions has been identified in individuals with RFC1 CANVAS / spectrum disorder [Cortese et al 2019].

Other Common Hereditary Ataxias

Table 3.

Most Common Hereditary Ataxias (Excluding Nucleotide Repeat Disorders)

Gene 1MOIPhenotypeOther Phenotypic Features / CommentsDesignation / GeneReview / OMIM
AtaxiaSpasticity
AFG3L2 AD++Ophthalmoparesis, slow saccades, ptosis 3SCA28 (OMIM 610246)
ARSCAR5 (OMIM 614487)
ANO10 AR++Downbeat nystagmus, fasciculationsSCAR10 (OMIM 613728)
APTX AR+Early-onset ataxia, oculomotor apraxia, extrapyramidal features, sensorimotor neuropathy, hypoalbuminemia; secondary coenzyme Q10 deficiency (See Primary Coenzyme Q10 Deficiency.) Ataxia with Oculomotor Apraxia Type 1
ATM AR+Early-onset ataxia, oculomotor apraxia, extrapyramidal features, immunodeficiency, cancer risk, ↑ alphafetoprotein Ataxia-Telangiectasia
CACNA1A 2AD+Episodic ataxia type 2 (OMIM 108500)
ITPR1 AD+Adult onset, slowly progressiveSCA15/16 (OMIM 606658)
AD 3+Congenital, non-progressiveSCA29 (OMIM 117360)
KCNC3 AD 3+Adult onset, slowly progressive SCA13
Congenital, non-progressive
KCND3 4AD+SCA19/22 (OMIM 605411)
PRKCG AD+ SCA14
SACS AR++Early-onset ataxia w/spastic paraparesis & axonal-demyelinating sensorimotor neuropathy; hypointense pontine stripes on T2-weighted MRI 5ARSACS (SPAX6)
SETX 6AR++Early-onset ataxia, oculomotor apraxia w/↑ alpha-fetoprotein 5Ataxia with Oculomotor Apraxia Type 2 (SCAR1)
SPG7 AR++Variable spasticity & cerebellar ataxia 5 Spastic Paraplegia 7
SPTBN2 AD+SCA5 (OMIM 600224)
ARSCAR14 (OMIM 615386)
SYNE1 7AR++Cerebellar ataxia, variable spasticity, & further multisystemic neurologic damage 5ARCA1 (SCAR8) (See SYNE1 Deficiency.)

AD = autosomal dominant; ARCA = autosomal recessive cerebellar ataxia; MOI = mode of inheritance; SCA = spinocerebellar ataxia; SCAR = spinocerebellar ataxia, autosomal recessive; SPAX = spastic ataxia, autosomal recessive

1.

Genes are listed in alphabetic order.

2.
3.

The disorder may occur as the result of a de novo pathogenic variant.

4.

Allelic disorder: Brugada syndrome

5.
6.
7.

Allelic phenotype: arthrogryposis multiplex congenita (See SYNE1 Deficiency.)

Potentially Treatable Hereditary Ataxias

Table 4.

Genetic Causes of Vitamin E Deficiency (Treatable with Vitamin E Replacement)

Gene 1MOIPhenotypic Features in Addition to Ataxia / CommentsDesignation / GeneReview / OMIM
ANGPTL3 ARNeuropathy, retinopathy, acanthocytosisFamilial combined hypolipidemia (OMIM 6050192
APOB AR 3

APOB-Related Familial Hypobetalipoproteinemia

MTTP ARLarge fiber sensory neuropathy, retinopathy, acanthocytosisAbetalipoproteinemia (Bassen-Kornzweig disease)
TTPA ARProprioceptive sensory loss, absent DTR Ataxia w/Vitamin E Deficiency

AR = autosomal recessive; DTR = deep tendon reflex; MOI = mode of inheritance

1.

Genes are listed in alphabetic order.

2.
3.

APOB-related familial hypobetalipoproteinemia caused by homozygous (or compound heterozygous) pathogenic variants in APOB is inherited in an autosomal recessive manner.

Table 5.

Primary Coenzyme Q10 (CoQ10) Deficiency (Possibly Responsive to CoQ10 Replacement)

Gene 1MOIOther Phenotypic Features / CommentsDesignation / GeneReview / OMIM
COQ2 ARSRNS, retinitis pigmentosa, SNHL, hypertrophic cardiomyopathy, ragged red muscle changes, seizures, lactic academia 2COQ10D1; Primary CoQ10 Deficiency
AD
AR
A small number of persons of Japanese ancestry w/multiple system atrophy type C have biallelic or heterozygous COQ2 pathogenic variants.OMIM 146500
COQ4 ARSimilar to COQ2-related CoQ10 deficiency 2COQ10D7; Primary CoQ10 Deficiency
COQ6 ARSimilar to COQ2-related CoQ10 deficiency; SRNS, SNHL 2COQ10D6; Primary CoQ10 Deficiency
COQ8A ARSeizures 2COQ10D4; Primary CoQ10 Deficiency; SCAR9 (OMIM 612016)
PDSS1 ARSimilar to COQ2-related CoQ10 deficiency 2COQ10D2; Primary CoQ10 Deficiency

AD = autosomal dominant; AR = autosomal recessive; MOI = mode of inheritance; SNHL = sensorineural hearing loss; SRNS = steroid-resistant nephrotic syndrome

1.

Genes are listed in alphabetic order.

2.

Onset usually in infancy or early childhood

3. Evaluation Strategies to Identify the Genetic Cause of Hereditary Ataxia in a Proband

Establishing a specific genetic cause of primary hereditary ataxia (as defined in this chapter):

  • Can aid in discussions of prognosis (which are beyond the scope of this GeneReview) and genetic counseling;
  • Usually involves a medical history, physical examination, family history, and genomic/genetic testing.

Medical History

Most of the common primary hereditary ataxias start similarly with an unsteady gait, imbalance or "dizziness," unexpected falls, clumsiness, and tremors.

Distinctive features of the medical history that could suggest a specific diagnosis (see Table 1 and Table 3) include the following:

  • Age of onset:
    • After age 50 years: SCA6
    • Before age 20 years: Friedreich ataxia, ataxia with oculomotor apraxia types 1 and 2
    • Before age five years: ataxia-telangiectasia
    • Infantile: SCA2, SCA7
  • Onset with episodic features: SCA6, the episodic ataxias
  • Associated with:
    • Retinopathy: SCA7
    • Seizure disorder: SCA10, infantile-onset SCA7, DRPLA
    • Dementia: SCA2, SCA17, DRPLA
    • Severe dizziness or vertigo: SCA3, SCA6, RFC1 CANVAS / spectrum disorder
    • Muscle cramping: SCA2, SCA3
    • Scoliosis, pes cavus, cardiomyopathy: Friedreich ataxia
    • Immunodeficiency or cancer: ataxia-telangiectasia

Physical Examination

All the primary hereditary ataxias have cerebellar features, but some have specific cerebellar or extracerebellar changes on examination that can suggest a specific diagnosis (see Table 1 and Table 3). In addition to the information provided in the medical history above, the following may be observed:

  • Early presence of slowed oculomotor saccades: SCA2, SCA7
  • Ophthalmoplegia: SCA1, SCA2, SCA3
  • Oculomotor apraxia: ataxia-telangiectasia, ataxia with oculomotor apraxia types 1 and 2
  • Fixation instability (saccade intrusions) in primary gaze: Friedreich ataxia
  • Ocular conjunctival and skin telangiectases: ataxia-telangiectasia
  • Downbeat nystagmus: SCA6 and episodic ataxia type 2
  • Central or peripheral vestibular involvement: SCA3, SCA6, RFC1 CANVAS / spectrum disorder
  • Motor unit fasciculations: SCA2, SCA3
  • Peripheral neuropathy: SCA3, RFC1 CANVAS / spectrum disorder
  • Spasticity: SCA1, SCA3, SCA7
  • Extrapyramidal signs: SCA1, SCA2, SCA3, SCA17, DRPLA
  • Absent deep tendon reflexes and upgoing toes: Friedreich ataxia

Family History

A three-generation family history should be taken with attention to relatives with manifestations of hereditary ataxia and documentation of relevant findings through direct examination or review of medical records, including results of molecular genetic testing, neuroimaging studies, and autopsy examinations. Findings in the family that may assist in narrowing the scope of relevant hereditary ataxias include the following:

  • Earlier onset and increasing severity of disease in subsequent generations suggest an autosomal dominant nucleotide repeat disorder associated with anticipation (see Table 1).
  • An affected parent or grandparent suggests autosomal dominant inheritance.
  • No male-to-male transmission of the disorder suggests X-linked inheritance.
  • Affected sibs or consanguinity suggests autosomal recessive inheritance. Note: In communities with a high prevalence of an autosomal recessive ataxia (e.g., the ARSACS carrier frequency in the Saguenay–Lac-Saint-Jean region of Quebec is 1:21), affected individuals in two or more generations may be observed.
  • Late-onset cerebellar ataxia in a grandfather who has a grandson with intellectual disability suggests fragile X-associated tremor/ataxia syndrome in the grandfather.
  • Note: In the absence of a molecularly confirmed ataxia, reports of balance problems in a grandparent, parent, or sib do not necessarily indicate a shared genetic cause. Multifactorial and acquired cerebellar disorders, which are four to five times more common than inherited ataxias, can confuse a family history.

Molecular Genetic Testing

Nucleotide repeat disorders. Establishing the diagnosis in an individual with one of the nucleotide repeat disorders (see Table 1) requires identification of an expanded nucleotide repeat and determination of the nucleotide repeat size for each disorder (see Table 2).

Note that commercially available multigene panels that rely on sequence analysis alone will not identify these nucleotide repeat expansions; thus, specific assays are required to analyze the nucleotide repeat in each gene of interest. Options offered by some laboratories:

  • A multigene "repeat expansion" panel to specifically identify nucleotide repeat expansions
  • A multigene ataxia panel that combines both repeat expansion testing and sequence-based testing analysis

Non-nucleotide repeat disorders. Establishing the diagnosis of one of the disorders listed in Table 3 requires detection of a sequence variant. Molecular genetic testing approaches can include a combination of gene-targeted testing (multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing). Gene-targeted testing requires the clinician to hypothesize which gene(s) are likely involved, whereas genomic testing does not.

  • A "sequence-based" ataxia multigene panel is most likely to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. 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) 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. (3) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests. (4) Sequencing-based tests including exome sequencing do not readily detect nucleotide repeat expansions.
    For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
  • Comprehensive genomic testing is an option that does not require the clinician to determine which gene(s) are likely involved. Exome sequencing is most commonly used; genome sequencing is also possible. Note that sequencing-based tests including exome sequencing do not readily detect nucleotide repeat expansions.
    For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.

4. Genetic Counseling of Family Members of an Individual with Hereditary Ataxia

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

The hereditary ataxias included in this overview 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.

For hereditary ataxias that are nucleotide repeat disorders, select the relevant link to the GeneReview chapter (if available) in Table 1 for genetic counseling issues.

The genetic counseling issues for the other common hereditary ataxias (see Table 3) are discussed below.

Autosomal Dominant Inheritance – Risk to Family Members

Parents of a proband

Sibs of a proband. The risk to the sibs of the proband depends on the clinical/genetic status of the proband's parents:

Offspring of a proband. Each child of an individual with autosomal dominant hereditary ataxia has a 50% chance of inheriting the pathogenic variant.

Other family members. The risk to other family members depends on the status of the proband's parents: if a parent has the pathogenic variant, the parent's family members may be at risk.

Autosomal Recessive Inheritance – Risk to Family Members

Parents of a proband

Sibs of a proband

Offspring of a proband. The offspring of an individual with autosomal recessive hereditary ataxia 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 of a pathogenic variant.

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

Resources

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
    United Kingdom
    Phone: 0800 995 6037; +44 (0) 20 7582 1444 (from abroad)
    Email: help@ataxia.org.uk
  • National Ataxia Foundation
    Phone: 763-553-0020
    Fax: 763-553-0167
    Email: naf@ataxia.org
  • Spanish Ataxia Federation (FEDAES)
    Spain
    Phone: 34 983 278 029; 34 985 097 152; 34 634 597 503
    Email: sede.valladolid@fedaes.org; sede.gijon@fedaes.org; sede.bilbao@fedaes.org
  • Associazione Nazionale SiIndromi Atassiche (A.I.S.A.) O.N.L.U.S.
    Via Sara 12
    16039
    Italy
    Fax: 39 178 2279678
  • A-T Children's Project
    Ataxia-Telangiectasia Children's Project
    Phone: 800.5.HELP.A-T (800.543.5728); 954-481-6611
  • euro-ATAXIA (European Federation of Hereditary Ataxias)
    United Kingdom
    Email: lporter@ataxia.org.uk
  • Friedreich's Ataxia Research Alliance (FARA)
    Phone: 484-879-6160
    Fax: 484-872-1402
    Email: info@CureFA.org
  • NCBI Genes and Disease
  • Spinocerebellar Ataxia: Making an Informed Choice about Genetic Testing
    Booklet providing information about Spinocerebellar Ataxia

5. Management of Hereditary Ataxia

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs of an individual diagnosed with a hereditary ataxia, the evaluations summarized in Table 6 (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 6.

Recommended Evaluations Following Initial Diagnosis in Individuals with a Hereditary Ataxia

SystemEvaluationComment
Neurologic Assessment by neurologist for:
  • Cerebellar motor dysfunction (gait & postural ataxia, dysmetria, dysdiadochokinesis, tremor, dysarthria, nystagmus, saccades, & smooth pursuit)
  • UMN &/or LMN dysfunction (weakness, spasticity, Babinski signs, hyperreflexia, amyotrophy, fasciculations)
  • Vibration loss or polyneuropathy based on clinical findings
  • Use standardized scale to establish baseline for ataxia (SARA). 1
  • Consider electrophysiologic studies (EMG & NCS) to detect neurogenic changes or signs of neuropathy.
  • Brain MRI to evaluate presence & severity of cerebellar atrophy
Refer to neuromuscular clinic (OT / PT / rehab specialist).To assess gross motor & fine motor skills, ambulation, & need for adaptive devices & PT
Speech For those w/dysarthria &/or other speech/language difficultiesRefer to SLP.
Feeding For those w/frequent choking or severe dysphagia, assess nutritional status & aspiration risk.Consider involving a gastroenterology/nutrition/feeding team.
Respiratory For those w/respiratory symptoms or muscular involvement, obtain pulmonary function tests & sleep study.Consider involving pulmonary specialist & sleep specialist.
Cognitive/
Psychiatric
Assess for cognitive dysfunction assoc w/cerebellar cognitive & affective syndrome (executive function, language processing, visuospatial/visuoconstructional skills, emotion regulation).Consider use of:
  • CCAS scale 2 to evaluate cognitive & emotional involvement;
  • Psychiatrist, psychologist, neuropsychologist if needed.
Musculoskeletal Assess for skeletal involvement, mainly scoliosis & pes cavus.Consider involving orthopedic specialist or orthotics specialist.
Genetic counseling By genetics professionals 3To inform affected persons & their families re nature, MOI, & implications of their diagnosis to facilitate medical & personal decision making
Family support
& resources
Assess need for:

CCAS = cerebellar cognitive affective syndrome; EMG = electromyogram; LMN = lower motor neuron; NCS = nerve conduction study; OT = occupational therapy/therapist; PT = physical therapy/therapist; SARA = Scale for the Assessment and Rating of Ataxia; SLP = speech-language pathologist; UMN = upper motor neuron

1.
2.
3.

Medical geneticist, certified genetic counselor, certified advanced genetic nurse

Treatment of Manifestations

The goals of supportive care are to maximize function and reduce complications. Depending on the clinical manifestations, affected individuals benefit from supportive care by a multidisciplinary team of specialists including neurologists, occupational therapists, physical therapists, physiatrists, orthopedists, nutritionists, speech-language pathologists, pulmonologists, and mental health specialists.

Table 7.

Treatment of Manifestations in Individuals with a Hereditary Ataxia

ManifestationTreatmentConsiderations/Other
Ataxia Care by physiatrist, OT/PT
  • Consider adaptive devices to maintain/improve independence in mobility (e.g., canes, walkers, ramps to accommodate motorized chairs), feeding (e.g., weighted eating utensils), & dressing (e.g., dressing hooks).
  • PT (balance exercises, gait training, muscle strengthening) to maintain mobility & function 1
  • OT to optimize ADL
  • Inpatient rehab w/OT/PT may improve ataxia & functional abilities in persons w/degenerative ataxias. 2, 3
  • Weight control to avoid obesity
  • Home adaptations to prevent falls (e.g., grab bars, raised toilet seats)
Pharmacologic treatmentConsider riluzole (100 mg/d 3), the only drug shown to improve ataxia symptoms in persons w/ataxia of mixed etiologies; use requires monitoring of liver enzymes.
Transcranial magnetic stimulationConsider transcranial magnetic stimulation over cerebellum, 2 which may improve cerebellar motor signs after 21 daily treatments (tested in persons w/various causes of spinocerebellar degeneration).
UMN involvement (spasticity) Pharmacologic treatmentBaclofen, tizanidine, or dantrolene may relieve muscle spasms & spasticity.
Dysarthria Speech/language therapyConsider alternative communication methods as needed (e.g., writing pads & digital devices).
Dysphagia Modify food consistency to ↓ aspiration risk.Video esophagram may help define best consistency.
Poor weight gain Nutrition assessmentConsider nutritional & vitamin supplementation to meet dietary needs.
Scoliosis / Skeletal involvement Surgical treatmentRefer to orthopedic surgeon when required.
Cognitive/
Psychiatric
Pharmacologic treatmentStandard treatment for psychiatric manifestations (e.g., depression, anxiety, & psychosis)
Psychotherapy / neuropsychological rehabConsider cognitive & behavioral therapy, incl Goal Management Training®4

ADL = activities of daily living; OT = occupational therapy/therapist; PT = physical therapy/therapist; UMN = upper motor neuron

1.
2.
3.
4.

Surveillance

There are no published surveillance guidelines for hereditary ataxias in general.

Table 8.

Recommended Surveillance for Individuals with a Hereditary Ataxia

System/ConcernEvaluationFrequency
Neurologic
  • Neurologic assessment for progression of ataxia, UMN or LMN signs, & history of falls
  • Monitor ataxia progression w/standardized scale (SARA). 1
  • Physiatry, OT/PT assessment of mobility, & self-help skills as they relate to ataxia, spasticity, & weakness
Annually; more often for an acute exacerbation
Dysarthria Need for alternative communication method or speech therapyPer symptom progression
Dysphagia Assess aspiration risk & feeding methods.
Cognitive/
Psychiatric
Evaluate mood, signs of psychosis, & cognitive complaints to identify need for pharmacologic & psychotherapeutic interventions.Per symptom progression & development of psychiatric symptoms
Family/
Community
Assess family need for social work support (e.g., palliative/respite care, home nursing, other local resources), care coordination, or follow-up genetic counseling if new questions arise (e.g., family planning).At each visit

LMN = lower motor neuron; OT = occupational therapy; PT = physical therapy; SARA = Scale for the Assessment and Rating of Ataxia; UMN = upper motor neuron

1.

Chapter Notes

Author Notes

As a Clinical Professor of Neurology, Dr Perlman is involved in the diagnosis and treatment of cerebellar ataxia and other neurogenetic disorders. She conducts research on collaborative natural history, biomarker, and clinical trials in spinocerebellar ataxia, Friedreich ataxia, ataxia-telangiectasia, late-onset Tay-Sachs disease, and Huntington disease.

Dr Perlman can be reached at:

UCLA Neurology Services
300 UCLA Medical Plaza, Suite B200, Los Angeles, CA, 90095
Phone: 310-794-1195
Fax: 310-794-7491
Web page: www.uclahealth.org/neurology/neurogenetics

Acknowledgments

The author acknowledges the following organizations and people:

  • National Ataxia Foundation, sponsor of grants for collaborative natural history and biomarker studies
  • Friedreich's Ataxia Research Alliance, sponsor of grants for collaborative natural history and biomarker studies
  • The Smith Family Foundation, the Lapin Family Fund, the Bettencourt Fund, the John Paul Jr. Fund, and the Wapner Fund
  • Our patients and their families, for their willingness to work with us and to share with us their ideas and hopes

Author History

Thomas D Bird, MD; University of Washington (1998-2022)
Susan Perlman, MD (2022-present)

Revision History

  • 16 June 2022 (bp) Comprehensive update posted live
  • 5 March 1999 – 25 July 2019 (tb) >70 revisions initiated by author Tom Bird
  • 11 June 2015 (tb/aa) Revision: addition of SNX4 (SCAR20), RNF216 (Gordon Holmes syndrome), and citations
  • 16 October 2014 (aa) Revision: addition of SCA40, caused by mutation of CCDC88C
  • 14 August 2014 (me) Comprehensive update posted live
  • 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
  • 27 June 2007 (me) Comprehensive update posted live
  • 8 February 2005 (me) Comprehensive update posted live
  • 14 October 2004 (tb/cd) Revision
  • 27 May 2004 (ca) Revision: addition of SCA world map (Figure 1)
  • 27 February 2003 (me) Comprehensive update posted live
  • 28 October 1998 (me) Overview posted live
  • 23 June 1998 (tb) Original submission

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