1146 A Pediatric Patient with Familial Type-1-Narcolepsy

Abstract

Human familial Type-1-narcolepsy was first reported in 1877. Animal models have revealed autosomal recessive pattern of inheritance. Tight genetic association with (HLA)-DQB1*06:02 is evident with up to 98% of patients testing positive1. Other genetic associations including hypocretin receptor mutations, HLA-DR, -DQ subtypes with variable phenotypes have been identified in different ethnic groups. Our patient is a 15-year-old female with a 1-year history of excessive daytime sleepiness and “fainting spells”. The episodes occur at various times of the day. Over the past week, she had 9 episodes during which she was awake but unable to communicate. Episodes were preceded by strong emotions such as laughter. Patient reported hypnagogic hallucinations. She reported daytime sleepiness with a pediatric daytime sleepiness score of 29. Patient takes multiple refreshing naps during the day. The family denied any history of infections or head trauma prior to developing current symptoms. Family history was significant for multiple family members over multiple generations with similar symptoms and her sister had a polysomnography (PSG) and mean sleep latency test (MSLT) confirming a diagnosis of type-1-narcolepsy. Our patient underwent formal testing with an overnight PSG which was negative for sleep disordered breathing. This was followed by a MSLT, revealing >2 SOREMPs and mean sleep latency 6.2 minutes, confirming the diagnosis of type-1-narcolepsy. (HLA)-DQB1*0602 was negative. Family members are currently undergoing genetic testing. Our case demonstrated a strong family history of type-1-narcolepsy symptoms among multiple members spanning over multiple generations with patient testing negative for (HLA)-DQB1*06:02. This suggests possible heterogeneity in the presentation of narcolepsy. One study identified a rare subtype HLA-DPB1*09:01 in negative (HLA)-DQB1*06:02 with low CSF hypocretin2. Although genetic testing is not routinely performed, there is a need to identify genotype and phenotype variations in patients with significant family history of narcolepsy.