A family of episodic ataxia type 2: no evidence of genetic linkage to the CACNA1A gene.

Episodic ataxia type 2 (EA2) has been reported to result from mutations in the CACNA1A gene, located on chromosome 19p13. We describe a family with episodic ataxia, clinically indistinguishable from EA2, that was not caused by CACNA1A gene mutation. The proband is an 11-year-old boy, who has had 6 cerebellar ataxic attacks since 8 years of age. His attacks occurred almost monthly, lasting for 2 to 3 days. He was treated successfully with acetazolamide. His identical twin, mother and grandmother developed ataxic attacks at age 10, 34, and 50, respectively. The symptoms in his grandmother improved gradually without medication. His mother and identical twin took acetazolamide with a good response. We examined the CACNA1A gene for this family but did not detect any mutations. Furthermore, there was no evidence of genetic linkage between the CACNA1A gene and the symptomatic patients in this family. This suggests that the cause of EA2 can be heterogeneous, that is, defects of genes other than CACNA1A might be the cause of EA2.