ABSTRACT
A strong familial component in narcolepsy was suggested in the original reports of narcolepsy by Westphal and Fisher in the 1870s (1). The proband described by Westphal had an affected mother, and the proband of Fisher had a sister affected by narcolepsy. We now know that narcolepsy most commonly occurs sporadically, rarely in families, and only 1% to 2% of first-degree relatives develop narcolepsy. Despite the low overall risk, first-degree relatives have a 10-40 times greater risk for the development of the disorder than general population. HLA antigen DQB10602 is the major susceptibility factor in the development of narcolepsy/cataplexy, as the majority of cases (90% to 100%) are found in association with this allele, in contrast to an allele frequency of 12% to 38% in the general population (1). However, the increased risk is not solely explained by co-inheritance of the HLA allele, thus other loci are likely to be involved in triggering the process or modulating the susceptibility conferred by HLA DQB10602. Other precipitating environmental factors are also thought to be required, as only 25% to 31% of monozygotic twins are concordant for narcolepsy, and due to the high prevalence of the DQ allele in the general population (1).
