A case of monozygotic twins with hereditary spastic paraplegia type 4 and epilepsy, of whom only one developed narcolepsy type 1

Summary We report a case of monozygotic twin sisters with hereditary spastic paraplegia type 4 (SPG4) and epilepsy, only one of whom had a diagnosis of narcolepsy type 1 (NT1). The older sister with NT1 exhibited excessive daytime sleepiness, cataplexy, sleep‐onset rapid eye movement period in the multiple sleep latency test, and decreased orexin levels in cerebrospinal fluid. Both sisters had HLA‐DRB1*15:01‐DQB1*06:02 and were further identified to have a novel missense mutation (c.1156A > C, p.Asn386His) in the coding exon of the spastin (SPAST) gene. The novel missense mutation might be involved in the development of epilepsy. This case is characterised by a combined diagnosis of SPG4 and epilepsy, and it is the first report of NT1 combined with epilepsy and genetically confirmed SPG4. The fact that only one of the twins has NT1 suggests that acquired and environmental factors are important in the pathogenesis of NT1.