New Clinical Phenotype Caused by a Novel SLC6A1 Mutation with Marked Responsiveness to Zonisamide (P4.179)

Objective: To report a new clinical phenotype associated with a previously unreported SLC6A1 mutation. Background: Pathogenic variants of the SLC6A1 gene, coding for GABA transporter protein 1, have recently been reported to cause drug resistant myoclonic-astatic epilepsy and is associated with generalized spike/polyspike slow wave discharges. Design/Methods: Retrospective review of the medical records. Results: 3-year-old boy who sat at age 6 months, walked at 18 months and said his first word at 2 years. He developed at the age of 9 months, episodes (10/day) of sudden initial complete loss of tone followed by 2–3 seconds of persistent atonia, or eyelid blinking or tonic clonic activity. EEG showed bilateral independent multifocal frontal and temporal spikes and no ESES. Seizures did not improve on levetiracetam and the patient was noted to have poor social interaction and poor eye contact. At the age of 2.5 years he was started on Zonegran 3 mg/kg/day and within a few days his seizures dropped to 2–3/day, his eye contact improved and his vocabulary quickly increased to 20 words. The dose was increased about a month later to 6 mg/kg/day and he had further marked improvement: He started to follow instructions, had further improved eye contact and three months later had endured only 3 seizures one of which was precipitated by an illness, and another after an LP. He was noted to become much more social with increased energy and improved social interaction. In another 3 months while on the same dosage he was seizure fee except for rare 1–2 second staring spells (1–2/week), likely behavioral, or single mild extremity myoclonic jerks (1–2/week). Extensive metabolic workup was negative. Whole Exome Sequencing showed a novel c.196A>G, p.Asn66Asp variant strongly predicted to be disease causing. Conclusions: Our findings expand the epilepsy phenotype caused by SLC7A1 mutations. Disclosure: Dr. Helseth has nothing to disclose. Dr. Mohamad has nothing to disclose.