Objective: We describe two cases, a father-daughter pair, of CACNA1A mutation with task specific dystonia as an early feature. The father otherwise had a phenotype of adult-onset pure cerebellar ataxia.

Background: Mutations in CACNA1A, even in pedigrees demonstrating the same mutation, are understood to present with a heterogeneous spectrum of phenotypes including familial hemiplegic migraine, episodic ataxia type 2 and spinocerebellar ataxia type 6.

Methods: Case 1: A 39-year-old male, referred for assessment of progressive cerebellar ataxia, first noted poor balance as a teenager. In his 20s he experienced a decline in handwriting with features of tremor, cramping, pain and abnormal posturing when writing. Symptoms were alleviated by touching the wrist with the left hand. MRI brain revealed cerebellar atrophy. Testing for vitamin E, frataxin, fragile X-associated tremor/ataxia syndrome, DYT1, SPG3A, SPG4, SPG6 were negative. Triplet repeat testing for SCA 1, 2, 3, 6, 7 was negative.

Case 2:  6 years later his 8-year-old daughter was assessed due to concerns regarding balance. She had difficulty riding a bike, climbing stairs, mild bilateral past pointing and hypometric saccades. She experienced in-turning of one foot when descending down stairs and required an orthotic.

Genetic testing in the proband and his daughter for CACNA1A revealed a c.1748G>A missense mutation in chromosome 19, resulting in an arginine583 to glycine substitution in both individuals.

Results: Dystonia is not typically associated with CACNA1A mutation but there are several reports in the literature. CACNA1A null mouse models exhibited dystonia early in addition to absence seizures and ataxia. Dystonia has been described both ictally and inter-ictally in cases with the episodic ataxia phenotype. It has also been observed in spinocerebellar ataxia type 6 resulting from CAG expansion in exon 47. In the pediatric population cases of dystonia are also reported in association with the episodic ataxia phenotype. Furthermore, studies in benign paroxysmal torticollis of infancy have also revealed mutations in the CACNA1A.

Conclusions: Thus dystonia can be an early aspect of the clinical phenotype of CACNA1A.  This clinical observation also indicates a relationship between dystonia and abnormal calcium signaling and further studies may elucidate additional insights.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/focal-dystonia-as-an-early-symptom-of-cacna1a-mutation-case-report-and-literature-review/