Episodic Ataxia Type 2 – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY

Review
In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2020.
[updated ].

Excerpt

NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.

Clinical characteristics: Episodic ataxia type 2 (EA2) is characterized by paroxysmal attacks of ataxia, vertigo, and nausea typically lasting minutes to days in duration. Attacks can be associated with dysarthria, diplopia, tinnitus, dystonia, hemiplegia, and headache. About 50% of individuals with EA2 have migraine headaches. Onset is typically in childhood or early adolescence (age range 2-32 years). Frequency of attacks can range from once or twice a year to three or four times a week. Attacks can be triggered by stress, exertion, caffeine, alcohol, fever, heat, and phenytoin; they can be stopped or decreased in frequency and severity by administration of acetazolamide or 4-aminopyridine. Between attacks, individuals may initially be asymptomatic but commonly develop interictal findings that can include nystagmus, pursuit and saccade alterations, and ataxia.

Diagnosis/testing: The diagnosis of EA2 is established by identification of a heterozygous pathogenic variant in CACNA1A.

Management: Treatment of manifestations: Acetazolamide is effective in controlling or reducing the frequency and severity of attacks in most individuals; typical starting dose is 125 mg a day given orally, but doses as high as 500 mg twice a day may be required. Acetazolamide is generally well tolerated; the most common side effects are paresthesias of the extremities, rash, and renal calculi. Acetazolamide does not appear to prevent the progression of interictal symptoms. Studies have also demonstrated that 4-aminopyridine in doses of 5-10 mg/3x/day can also be effective in reducing attack frequency and duration.

Surveillance: Annual neurologic examination.

Agents/circumstances to avoid: Phenytoin has been reported to exacerbate symptoms.

Genetic counseling: EA2 is inherited in an autosomal dominant manner. Most individuals with a diagnosis of EA2 have an affected parent. The proportion of cases caused by de novo pathogenic variants is unknown. Offspring of affected individuals have a 50% chance of inheriting the pathogenic variant. Prenatal testing is possible for pregnancies at increased risk for EA2 if the pathogenic variant has been identified in the family.

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