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Cacna1a mutation presenting with focal dystonia
  1. Jason Gu1,2,
  2. Kishore R Kumar1,3,4,
  3. Carolyn M Sue1,3
  1. 1Department of Neurology, Royal North Shore Hospital, St Leonards, NSW, Australia
  2. 2Neurology, The Wollongong Hospital, Wollongong, NSW, Australia
  3. 3University of Sydney, Camperdown, NSW, Australia
  4. 4Kinghorn Centre of Clinical Genomics, Garvan Institute of Medical Research, Sydney, NSW, Australia


Objectives Mutations in CACNA1A can present with a heterogeneous spectrum of phenotypes including familial hemiplegic migraine, episodic ataxia type 2 and spinocerebellar ataxia type 6. We describe a case of CACNA1A mutation, adult-onset pure cerebellar ataxia phenotype, with writer’s cramp as an early feature.

Case 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. Genetic testing for CACNA1A revealed a c.1748G>A missense mutation in chromosome 19 resulting in an arginine583 to glycine substitution.

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

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