Abstracts

Rationale: Expand the epilepsy phenotype of CACNA1A gene mutation in childhood. Epileptic encephalopathy and absence seizures are associated with CACNA1A mutation; however, to the best of our knowledge focal seizures with a CACNA1A mutation has not been previously reported. Methods: We present an infant with a de novo mutation in the CACNA1A gene with focal epilepsy, ataxia, and motor developmental delay. Results: I.T. is a 13 months old Caucasian girl born to a primigravida mother at 37 weeks via spontaneous vaginal delivery and uneventful pregnancy. She was first seen by neurology at the age of 6 months for episodes concerning for seizures. Mother described the baby waking up from sleep with a cry followed by jerking of hands and feet with eyes deviated to the right. No family history of seizures was reported. Parents had a non-consanguineous marriage. Initial exam showed mild motor delay and central hypotonia but no dysmorphism or neurocutaneous stigmata. Routine EEG, brain MRI, genetic/metabolic screening (chromosome microarray, organic acids and amino acids) were performed and were unremarkable. Episodes of interest persisted prompting re-admission. Repeat neurological exam demonstrated titubation, appendicular dysmetria in addition to central hypotonia. VEEG was performed and captured left temporal-occipital epileptiform discharges with intermittent slowing in the same region and an electro-clinical seizure (Figure 1). Our patient was started on phenobarbital with improvement of seizures. A comprehensive epilepsy gene panel demonstrated a CACNA1A mutation c.4177 G>A (p.V1393M). Targeted parental gene testing for CACNA1A was performed with no mutation found in either parent. At 3 and 6 months follow-up exam she had one breakthrough seizure requiring phenobarbital dose adjustment. Apparent motor delays secondary to prominent ataxia were noted in her physical exam and she continues to receive physical and occupational therapy. Conclusions: CACNA1A gene encodes a pore-forming subunit of the P/Q-type calcium channel and is linked to phenotypes of episodic ataxia type 2, familial hemiplegic migraine, and epileptic encephalopathy. Our subject has a de novo CACNA1A mutation with focal seizures and ataxia. Long term clinical, neuroimaging and EEG follow-up of the index case will help understand the natural course of this specific CACNA1A mutation. Funding: None