Copy Number Variant Associated with Familial Epilepsy with Wide Phenotypic Spectrum: A Case Series (P3-1.003)

Abstract

<h3>Objective:</h3> Not Applicable <h3>Background:</h3> Many patients with familial epilepsy lack identifiable genetic causes. We report a 29-year-old patient with autism and refractory seizures since age 16 years, along with her mother and two sisters who all have epilepsy with varying electroclinical phenotypes. <h3>Design/Methods:</h3> All four family members underwent genetic counseling and pedigree was generated. Three family members (Patient 1, 2 and 4 described below) underwent whole-genome sequencing (WGS). <h3>Results:</h3> WGS of patient, mother, and one sister revealed a 1.1 mb copy number gain of the X chromosome located at position (31,052,355–32,186,379) - including exons 45–79 of the <i>DMD</i> and <i>FTHL17</i> genes. Electroclinical phenotypes are detailed below: <h3>Patient 1 (Proband):</h3> 29-year-old patient with seizure onset at age 16 years and autism. Has multiple refractory seizure types including focal tonic and atonic seizures. Ictal EEG showed left frontocentral onset and diffuse attenuation. Patient is refractory on four anti-seizure medications (ASMs). <h3>Patient 2:</h3> 30-year-old sister with seizure onset since age 14 years. Seizures are bilateral tonic-clonic and focal with impaired awareness. Ictal EEG showed diffuse onset in both types. Patient is refractory on 3 ASMs. <h3>Patient 3:</h3> 32-year-old sister with epilepsy since age 20 years. Seizures are focal with impaired awareness. Ictal EEG showed independent seizures with left temporal and right frontotemporal onset. She is refractory on 2 ASMs. <h3>Patient 4:</h3> 57-year-old mother with seizure onset since age 19 years. Seizures are focal with impaired awareness. Ictal EEG demonstrates right frontoparietal onset. She is well controlled on 2 ASMs. <h3>Conclusions:</h3> We describe an X-linked copy number variant mutation associated with familial epilepsy. Family members have variable electroclinical phenotypes. Role of <i>DMD</i> or <i>FTHL17</i> genes in epileptogenicity is unclear. Emerging data has linked dystrophin to clustering of GABA-a receptors at the post-synaptic membrane, thought to regulate inhibitory input and neuronal activity which warrants further investigation. <b>Disclosure:</b> Dr. Pokharel has nothing to disclose. Dr. Przybycien has nothing to disclose. Karen Krajewski has nothing to disclose. Dr. Yang has nothing to disclose. Dr. Zutshi has nothing to disclose. Dr. Basha has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai.