Abstracts

Rationale: Epileptic spasms are a rare but significant cause of infantile epileptic encephalopathy. Epileptic spasms are classified into idiopathic or symptomatic depending on the presence or absence of underlying neurologic abnormalities. Patients with symptomatic epileptic spasms tend to be more resistant to treatment with worse developmental outcomes. It is important to identify an underlying pathology to prognosticate and perhaps select most appropriate treatment. The CACNA1E gene is involved in the expression of the alpha-1e subunit of R-type voltage-gated calcium channels. These channels play a known role in central nervous system excitatory synaptic potentials, and alterations in their function have been implicated in increased seizure susceptibility. Here we describe a patient with a novel CACNA1E gene variant associated with refractory symptomatic epileptic spasms. Methods: Review of the affected patient's medical record including neuro-imaging, metabolic studies, genetic testing, EEG and epilepsy monitoring were reviewed. Genedx database was reviewed regarding CACNA1E gene variations and similarly affected patients. Literature search performed using Pubmed for publications on infantile spasms and refractory infantile spasms. Results: Eight month old Hispanic male born at term after an uncomplicated pregnancy and delivery. He presented to the outpatient neurology clinic at Phoenix Children's Hospital at 38 days of life due to abnormal tone. He had bilateral cortical fisting since birth, and mixed hypotonia and hypertonia. At 3 months, he developed focal seizures, confirmed electrographically to be of right temporal onset, with inter-ictal multifocal epileptiform abnormalities. Magnetic resonance imaging (MRI) of the brain was unremarkable. He was treated with Keppra. Within the context of an inter-current infection, he presented with exacerbation of focal seizures and new onset of epileptic spasms. His EEG converted to modified hypsarrhythmia. Despite, high dose oral prednisolone (60mg/day), spasms persisted. He subsequently failed high dose Vigabatrin and Topiramate. He is now on the ketogenic diet and Lacosamide with modest reduction in spasm frequency. Repeat MRI showed interval increased ventricular size and subarachnoid spaces. Positron emission tomography (PET) did not show any obvious focus of altered metabolism. An extensive biochemical work up including plasma amino acids, urine organic acids, cerebrospinal fluid neurotransmitters, creatinine and guanidinoacetate was unrevealing. Chromosome microarray was normal. An 1148 gene epilepsy panel found a de novo, likely pathogenic missense variant (c.1054G>A, p.G325R) in the CACNA1E gene, an alpha-1E subunit of the R-type calcium channels. Conclusions: Epileptic spasms have been well described in specific genetic syndromes. Here we present a case of refractory infantile spasms due a mutation in a subunit of the R-type voltage-gated calcium channels. Three additional individuals with the same gene variant have been found in the Genedx data base (but not otherwise reported), and presented with hypotonia, seizures and infantile spasms. This case expands the phenotypic presentation of this newly described epilepsy gene, and provides information about a potential genotype-phenotype correlation. Funding: None