PHENOTYPIC VARIABILITY IN CASES WITH CACNA1A MUTATION

Introduction: The CACNA1A gene is located on the short arm of chromosome 19 and encodes the α1 subunit of voltage dependent calcium channels. CACNA1A is involved in neurotransmission and its mutations cause some chronic progressive and paroxysmal disorders.

Material-Methods: This multicentered study included 10 pediatric neurology clinics around Turkey and 28 patients enrolled. Patient characteristics and treatment responses were evaluated.

Results: Twenty-six patients involved in the study had epilepsy (92,9%) and 15,4% had drug-resistant epilepsy. Recurrent encephalopathy episodes were detected in 10% patients. Neurodevelopmental disorders (intellectual disability, autistic spectrum disorder, hypotonia) were reported 60,7% , ataxia was reported 60,7% (4 congenital ataxia, 4 episodic ataxia type 2 and 1 late-onset ataxia )and migraine was reported 17,9% of patients (3 familial hemiplegic migraine,2 migraine with or without aura). Cerebellar atrophy was reported in 30.8% of patients. Neurodevelopmental disabilities were significiantly more frequently in patients with ataxia. A spesific treatment regimen (acetazolamide, calcium channel blockers) was given to 25% of the patients and 75% of them had complete or partial response.

Conclusions: Mutations in the CACNA1A gene, which encodes p/q-type calcium channels expressed in cerebellar purkinje and granule cells, thalamus, cortex, and hippocampus result in a heterogeneous phenotypic spectrum. We believe that understanding mutation-spesific characteristics will be crucial to provide novel targeted treatment options in the future.
Keywords: cacna1a mutation, epileptic encephalopathies, ataxia, migraine