Abstracts

Rationale: Genetic testing is positive in approximately 14% of patients with Infantile Spasms (IS) (Wirrell et al., 2015). Genetic studies play an essential role in finding the etiology, treatment, anticipatory guidance for managing co-morbidities and also for long-term prognosis. Here we report two pediatric patients with reciprocal copy number variants (CNVs) at the 16p11.2 chromosomal locus, one with deletion and another with duplication with similar clinical presentation and outcome. Methods: We identified two patients who presented to our infantile spasm clinic with infantile spasms and mild gross motor developmental delay. We reviewed their medical history, details about seizure semiology, EEG, neuroimaging details, and genetic testing results. Results: Patient A is a 17 month old male who presented with IS at 9 months of age. He presented with Extensor spasms, in 1-2 clusters/day, with each cluster lasting for 5-10 minutes. Patient B is a 14 month old female who presented IS at 5 months of age. She presented with Flexor spasms, in 3-6 clusters/day, with each cluster lasting 1-7 minutes. Birth and past medical history were unremarkable for both patients; except, both had mild gross motor delay. For Patient A, family history was positive for epilepsy and speech delay on maternal side of the family (mom, sister, maternal grandfather and uncle). Both patients had a normal physical exam, brain MRI, and ophthalmologic exam. EEG showed hypsarrhythmia and epileptic spasm. Chromosomal microarray (CMA) showed chromosome 16p11.2 deletion for Patient A and 16p11.2 duplication for Patient B. Patient A was started on prednisolone. Clinical remission occurred; however the follow up EEG showed multifocal spikes so topiramate was added. Approximately 8-9 weeks from the onset, 24 hour VEEG showed both EEG and clinical remission. Patient B was started on ACTH. On Day 14 she continued to have subtle spasms and EEG showed multifocal epileptiform discharges, so topiramate was added. Approximately 8-9 weeks from the onset the 24 hour VEEG showed both EEG and clinical remission. Conclusions: Chromosome microarray (CMA) should be considered as the first line testing in the genetic work up for IS patients. Patients with copy number variants at the 16p11.2 are at risk for having developmental issues. Surprisingly, similar presentation of early onset (less than 12 months of age) infantile spasms with complete clinical remission was seen in patients with reciprocal CNVs at 16p11.2. Clinical study in large cohort of patients is needed to better understanding the prognostic value of CNVs in patients with IS and further, guide in formulating an aggressive epilepsy management plan. Funding: N/A