A - 49 Neuropsychological and Clinical Features of Ataxia Due to CACNA1A (P.1661H) Mutation: a Case Study.

OBJECTIVE: Mutations in CACNA1A gene can cause rare neurodegenerative conditions [spinocerebellar ataxia type 6 (SCA6); episodic ataxia type 2 (EA2)] which are caused by autosomal dominant mutations located on chromosome 19p13. Research suggests triplet repeat mutations in the CACNA1A gene are associated with SCA6 characterized by late onset, slowly progressive cerebellar ataxia. On the other hand, CACNA1A mutation with specific protein variant R1661H involvement is associated with EA2, characterized by early onset ataxia, which may be accompanied by vertigo, diplopia, dysarthria, and generalized weakness. We present a patient with genetically confirmed mutation in CACNA1A (p.1661H), not fitting the phenotype of EA2 despite associated variant.

METHOD: A retrospective review of the patient's medical record along with review of neuropsychological and neuroimaging reports.

RESULTS: Neuropsychological testing revealed a 79-year-old female who demonstrated executive, memory retrieval, construction and fine motor dexterity slowing along with dysfluency and anomia. Neurologic exam documented bilateral blepharospasm, with mild ataxia and speech disturbance (SARA total = 12). Neuroimaging revealed moderate cortical atrophy and chronic small vessel ischemia disease. Behavioral observations were notable for gait ataxia and dysarthria, as well as perseverative responding and anosognosia. She endorsed symptoms indicative of clinical levels of depression, apathy, anxiety and disinhibition. Her partner endorsed more notable executive dysfunction symptoms and functional impairment.

CONCLUSION: While the motor sequela is well documented, the neuropsychological impact is infrequently discussed in existing literature regarding CACNA1A (p.1661H) mutations. This case expands our understanding of the unique and varied phenotype associated with this unique CACNA1A gene variant.