Sleep disorders involve genetic susceptibility, environmental effects, and interactions between these factors [
10]. The heritability of sleep patterns has been reported previously in studies of monozygotic twins, which may assist in the identification of genes involved in sleep disorders [
11]. An understanding of sleep regulation at the molecular level is essential in the identification of targets for the treatment of sleep disorders. Although several familial cases of Kleine-Levin syndrome were reported [
4‐
8], no cases of twins affected with the disease reported [
9]. The cases of Kleine-Levin syndrome reported here are exceptional as they occur in monozygotic twins. For both patients the age of onset was similar and the symptoms and clinical course were typical. Actimetry demonstrated increased nocturnal activity and decreased daytime activity during symptomatic periods. PSG revealed low sleep efficiency during attacks, a decreased amount of SWS, sleep onset REM periods and sleep fragmentation. These PSG data are consistent with a previous report [
12]. Despite the reduced amplitude in the circadian rhythm of activity, a previous endocrinological study reported no link between an underlying circadian disorder and recurrent hypersomnia [
13]. Hypoperfusion [
14] or hyperperfusion [
15] of thalamus have been reported during the symptomatic period of Kleine-Levin syndrome with Tc-99 m ECD single photon emission tomography (SPECT) which suggest that there is an involvement of this brain tissue in the acute clinical presentation. Based on the generally young age of onset, the recurrence of symptoms and the frequent infectious trigger, an autoimmune etiology for Kleine-Levin syndrome has been suggested. In terms of genetic susceptibility, it has been suggested that the gene polymorphism of HLA-DQB1 is associated with recurrent hypersomnia [
16]. However, in a more recent study using a larger independent sample, HLA DR and DQ alleles did not differ between cases and control subjects [
17]. Both of the subjects in the case study reported here had been treated for an influenza infection at the onset of the first episode, but we did not identify DQB1*02. As for narcolepsy, which is a representative primary hypersomnia and has an established linkage with HLA subtype (HLA-DR2, DQB1*0602), increased onset following 2009 H1N1 winter influenza pandemic were reported recently [
18]. Association with HLA is now controversial but the involvement of an autoimmune process remains plausible. Genome-wide mapping studies should be performed using the known familial cases to search for potential linkage. Finally, while this manuscript was under review, another monozygotic twin pair concordant for Kleine-Levin syndrome is reported [
19]. Interestingly, they also found DQB1*0302/*0601 allele in the twins.