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Decline of CSF orexin (hypocretin) levels in Prader–Willi syndrome

Prader–Willi syndrome is a congenital neurodevelopmental disorder resulting from deletion of the paternal copies of genes within the chromosome region 15q11‐q13. Patients with Prader–Willi syndrome often exhibit excessive daytime sleepiness, excessive appetite, and obesity. As is the case in narcolepsy, orexin (hypocretin) may be responsible for these symptoms. However, reports showing cerebrospinal fluid orexin levels in Prader–Willi syndrome patients have been limited. The aim of this study was to examine the relationship between the characteristic symptoms of Prader–Willi syndrome and cerebrospinal fluid orexin levels. We clinically identified 14 Prader–Willi syndrome patients and examined their cerebrospinal fluid orexin levels. A total of 12 patients with a 15q11‐q13 deletion and two patients with maternal uniparental disomy of chromosome 15 were identified. A total of 37 narcoleptic patients and 14 idiopathic hypersomnia patients were recruited for comparison. Cerebrospinal fluid orexin levels (median [25–75 percentiles]) in the 14 Prader–Willi syndrome patients were intermediate (192 [161–234.5] pg/ml), higher than in the narcoleptic patients, but lower than in the idiopathic hypersomnia patients. Body mass index of the Prader–Willi syndrome patients was higher than in the narcoleptic and idiopathic hypersomnia patients. There was also a negative correlation between Epworth sleepiness scale scores and orexin levels in Prader–Willi syndrome patients. Decreased cerebrospinal fluid orexin levels in Prader–Willi syndrome may play an important role in severity of obesity and excessive daytime sleepiness. © 2016 Wiley Periodicals, Inc.