0991 Dual Therapy to Treat Circadian Rhythm Disturbance in Unique Genetic Mutation of Smith-Magenis Syndrome

Abstract

Abstract Introduction Smith-Magenis syndrome (SMS) is a rare disorder associated with several genetic mutations. Patients with SMS experience circadian rhythm sleep-wake disorders, which may lead to significant behavioral concerns. A proposed etiology of sleep disturbances is diurnal melatonin secretion. Treatment approaches aim at blocking the abnormal morning secretion of melatonin and providing exogenous melatonin in the evening. Report of case(s) We present a patient with SMS having persistent sleep-wake disturbance despite dual therapy with beta-1 adrenergic antagonist in the morning and over-the-counter melatonin at night. Our patient switched to therapy with beta-1 adrenergic antagonist in the mornings and melatonin receptor agonist, tasimelteon, at night with significant improvement. In addition, our patient has mutations in JAKMIP1 and ZBTB18 genes. ZBTB18 mutation is a novel mutation in the setting of clinical features of SMS. Conclusion To the authors’ knowledge, this is the first case report of successful combination therapy to optimize treatment of sleep-wake disturbances in patients with SMS. Support (if any)