HLA HAPLOTYPES, POLYSOMNOGRAPHY, AND PEDIGREES IN A CASE SERIES OF PATIENTS WITH NARCOLEPSY

An ongoing study of the genetics of narcolepsy ascertains families thr ough a case series of narcoleptic probands using diagnostic criteria c onsisting of 1) clinical history of excessive somnolence, 2) a mean sl eep latency on the multiple sleep latency test (MSLT) of less than 7.9 minutes, 3) the rapid eye movement (REM) sleep-related symptom of cat aplexy, 4) nocturnal polysomnography ruling out sleep apnea syndrome, and 5) two or more transitions to REM sleep on the MSLT. All probands and first-degree relatives received clinical and laboratory evaluation s as well as human leukocyte antigen (HLA) typing. Demographic charact eristics of the 32 probands are as follows: 17 males and 15 females; m ean age was 42.1 years (range 13-70 years). The polysomnographic data confirmed daytime sleepiness and increased tendency for REM sleep for the 32 probands. Nocturnal polysomnographic results are as follows: sl eep latency, 3.2 minutes; total sleep time, 442 minutes. MSLT results are as follows: sleep latency, 3.1 minutes; REM latency, 6.9 minutes; number of REM periods, 3.2. HLA typing revealed the presence of the HL A haplotypes, DRB115 and DQB1*0602, in 21 narcoleptic probands, with two African-Americans having the DQB10602 but not the DRB1*15 allele. Among the 57 relatives of the 32 probands, 1/31 females and 7/26 male s were found to be affected with narcolepsy (p < 0.02), which suggests a higher diagnostic rate in male relatives. The 21 probands who were positive for the DRB115 and DQB1*0602 haplotypes did not differ from the 10 probands who were negative for these alleles in terms of their nocturnal sleep parameters, MSLT findings, or clinical presentation. T hree families with multiple individuals affected with narcolepsy are p resented. Two families have more than one affected individual who does not have the high-risk HLA haplotype. In one of these families, the d isease is segregating independently of any HLA haplotype. In the third family, there is cosegregation with HLA DRB115 and DQB1*0602. One fa mily contains a pair of DNA-confirmed, monozygotic twins with narcolep sy who are discordant for cataplexy and have the HLA DR14(Dw9)/DQB105 03 and DR4(Dw4)/DQB10302 haplotypes.