Episodic Ataxia Type 1

Excerpt

Clinical characteristics: Episodic ataxia type 1 (EA1) is a potassium channelopathy characterized by constant myokymia and dramatic episodes of spastic contractions of the skeletal muscles of the head, arms, and legs with loss of both motor coordination and balance. During attacks individuals may experience a number of variable symptoms including vertigo, blurred vision, diplopia, nausea, headache, diaphoresis, clumsiness, stiffening of the body, dysarthric speech, and difficulty in breathing, among others. EA1 may be associated with epilepsy. Other possible associations include delayed motor development, cognitive disability, choreoathetosis, and carpal spasm. Usually, onset is in childhood or early adolescence.

Diagnosis/testing: Diagnosis is based on clinical findings, an electrophysiologic test of axonal superexcitability and threshold electrotonus, and/or the identification of a heterozygous pathogenic variant in KCNA1 by molecular genetic testing.

Management: Treatment of manifestations: Acetazolamide, a carbonic-anhydrase inhibitor, may reduce the frequency and severity of attacks in some but not all affected individuals. Anti-seizure medication may significantly reduce the frequency of attacks in some individuals. Supportive therapies, such as physical therapy, may reduce the risk of later-onset orthopedic complications. Routine treatment of seizure disorders, scoliosis, and developmental disabilities.

Prevention of primary manifestations: In addition to pharmacologic treatments, behavioral measures including avoidance of stress, abrupt movements, loud noises, and caffeine may be used to reduce disease manifestations in both symptomatic and asymptomatic individuals.

Prevention of secondary complications: Joint contractures can be prevented by appropriate physiotherapy.

Surveillance: Annual neurologic examination.

Agents/circumstances to avoid: Triggers of attacks, including physical exertion, emotional stress, and changes in environmental temperature; marked generalized myokymia has been reported during induction of anesthesia.

Pregnancy management: Affected women should be made aware that pregnancy may trigger attacks; possible loss of balance and falls could endanger the fetus. Several stressors that trigger attacks may cause breathing difficulties; thus, delivery by C-section should be considered.

Genetic counseling: EA1 is inherited in an autosomal dominant manner. Most individuals diagnosed with EA1 have an affected parent; however, de novo pathogenic variants have been reported. Each child of an individual with EA1 has a 50% chance of inheriting the KCNA1 pathogenic variant. Prenatal testing for a pregnancy at increased risk is possible if the pathogenic variant has been identified in an affected family member.