It was absent in 200 control chromosomes. It is predicted to result in an amino acid substitution at a highly phylogenetically conserved position, within a domain that plays a major role in the function of the channel. The Glu 1757 Lys missense mutation is likely to be pathogenic, causing episodic ataxia within a family whose phenotype is indistinguishable from EA2 except for a slightly later age of onset. Episodic ataxia type 1, a condition characterized by the association of brief ataxic spells and interictal myokymias, is caused by mutations within a voltage-gated potassium channel gene, KCNA1 . 1-9 Attacks last from several minutes to a few hours or days.
Clinical onset occurs usually during childhood or adolescence.
In a minority of patients, permanent symptoms are severe, and some patients may be wheelchair confined. Two families with a permanent progressive cerebellar ataxia, associated with paroxysmal ataxic episodes, and 1 family with pure episodic ataxia were shown to harbor CAG repeat expansions. Detailed clinical information was obtained from patient III-2 and 2 of his 3 sons who were clinically examined. His medical history was unremarkable except for a strabismus, which needed surgical repair at age 22 years. Ataxic spells were strongly stereotyped.