Adult-onset ataxia or developmental disorder with seizures: Two sides of missense changes in CACNA1A

Spinocerebellar ataxia type 6 (SCA6), familiar hemiplegic migraine (FHM), and episodic ataxia type 2 (EA2) are allelic disorders linked to CACNA1A mutations. CACNA1A encodes the alpha-1A subunit of neuronal voltage-dependent P/Q-type Ca2+ channels [1]. Some genotype-phenotype correlation has been observed with FHM usually caused by missense, EA2 by premature stop mutations, and SCA6 by CAG trinucleotide repeat expansions [2]. However, there is ample clinical overlap [3] and high intrafamilial phenotypic variability [4, 5]. Also, clinical manifestations beyond the “classical” phenotypes have recently been described including seizures and intellectual disability (ID) [6].

We report two patients with different missense mutations in CACNA1A, one presenting with an adult-onset SCA6-like phenotype, the other with infantile epilepsy, ID, ataxia, and myoclonus.

A 32-years-old male Portuguese patient (Patient 1) had a 3-year history of gradually developing diplopia, slurring speech...