A monozygotic twin pair discordant for narcolepsy and CSF hypocretin-1

Abstract

A genetic basis for narcolepsy is evidenced by a strong association with the HLA DQB1*0602 and the occasional familial occurrence.1 A major discovery was recently made through the identification of orexin/hypocretin deficiency.2,3⇓ While a single mutation in the prepro-hypocretin gene was reported in one atypical patient,3 undetectable levels of CSF hypocretin-1 were reported in most sporadic narcoleptics2 and a dramatic decrease of hypocretin neurons in few postmortem brains.3 Among the 16 monozygotic twin pairs described,1 only 6 are considered to be concordant and most of them were not completely documented. One HLA-DQB1*0602 positive twin pair concordant for narcolepsy was recently reported with normal levels of CSF hypocretin-1 and without any mutation in the hypocretin genes system.4 We studied the CSF hypocretin-1 in a HLA DQB1*0602 positive monozygotic twin pair discordant for narcolepsy. The twin sisters (brought up together until age 18 years) were the second and third born among three siblings, born in 1976. …