0814 Three Sleepy Siblings

Abstract

Abstract Introduction Narcolepsy type 1 is caused by destruction of hypocretin-producing neurons, likely via a T-cell mediated autoimmune process, and clinically identified either by CSF hypocretin deficiency or the presence of cataplexy. Individuals with narcolepsy type 1 have an underlying genetic predisposition attributed to the HLA DQB1*0602 gene. This genetic variant has been linked to increased propensity for sleepiness even in healthy adults. Relatives of patients with narcolepsy type 1 appear to be at increased risk for other disorders of hypersomnolence such as idiopathic hypersomnia. Here we describe three siblings, all positive for HLA DQB1*0602, who presented with distinct clinical features diagnostic for narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia. Report of Cases: A 15-year-old female was diagnosed with narcolepsy type 1 based on typical cataplexy, excessive daytime sleepiness, and mean sleep latency of 2 min with 2 SOREMPs on MSLT. Lumbar puncture (LP) performed 5 years after symptom onset showed low CSF hypocretin (9.3 pg/mL). Her older brother presented at age 21 with excessive sleepiness, somewhat atypical cataplexy, hypnagogic hallucinations, and sleep paralysis. MSLT showed mean sleep latency of 6 min with 5 SOREMPs. Despite the presence of cataplexy, LP performed 2 years after symptom onset showed normal CSF hypocretin (296.5 pg/mL) and he was diagnosed with narcolepsy type 2. Their younger sister presented at age 19 with progressive daytime sleepiness. PSG/MSLT showed mild OSA (RDI 9.2) and mean sleep latency of 6.5 min without SOREMPs. She does not have cataplexy, hypnagogic hallucinations, or sleep paralysis. The current findings are most consistent with idiopathic hypersomnia, although an LP to evaluate for hypocretin deficiency is an important next step. Similarly, a repeat LP in the brother might demonstrate change in hypocretin over time. Conclusion These cases may support a familial link between narcolepsy type 1, type 2, and idiopathic hypersomnia. The discordant hypocretin and cataplexy statuses of these siblings implies a mechanism for excessive sleepiness beyond hypocretin deficiency, possibly mediated by HLA DQB1*0602. Identifying the mechanisms of familial aggregation of sleepiness in the central disorders of hypersomnolence may shed light on the pathophysiology of these distinct disorders. Support (If Any)