Congenital Ataxia, Mental Retardation, and Dyskinesia Associated With a Novel CACNA1A Mutation

Abstract

The CACNA1A gene encodes the pore forming alpha-1A subunit of neuronal voltage-dependant P/Q-type Ca 2+ channels. Mutations in this gene result in clinical heterogeneity, and present with either chronic progressive symptoms, paroxysmal events, or both, with clinical overlap among the different phenotypes. The authors describe a seven year-old boy with mental retardation and congenital cerebellar ataxia that developed dyskinesia at the age of a few months, and recurrent episodes of coma following mild head trauma associated with motor and autonomic signs, from the second year of life. An extensive metabolic evaluation, interictal electroencephalography (EEG), and muscle biopsy were normal. Brain magnetic resonance imaging (MRI) during one of these episodes revealed edema of the right hemisphere and cerebellar atrophy. Genetic testing revealed a R1350Q mutation in the CACNA1A gene. This is a novel de novo mutation.Congenital cerebellar ataxia can be a result of CACNA1A mutations, especially when associated with recurrent unexplained coma.