*Neuropsychiatric Research Institute
Tokyo 162, Japan
arcolepsy is a sleep disorder with uniform symptoms, age of onset, familial appearance, unique pharmacological responses, long-term clinical course, personality changes, frequent sleep-onset REM periods, and strong association with human leucocyte antigens (HLA). The familial occurrence of narcolepsy was observed in 4.2% of our 451 narcoleptic patients. The segregation analysis of narcoleptic patients revealed that heritability of liability to narcolepsy was 0.3364. The 14 pairs of identical twins so far reported revealed that only 3 pairs were concordant for narcolepsy. This indicates that environmental factors are involved in the mechanism for the onset of narcolepsy.
In our serial 388 cases of narcolepsy, almost all patients had DR2/15 and DQ1/6. DNA analysis showed that all Japanese narcoleptic patients so far tested had DRB1*1501 and DQB 1*0602 in common. But we recently found two patients with narcoleptic symptoms without DR2.The differential diagnostic criteria for narcolepsy are most important. We propose "Essential Hypersomnia Syndrome (EHS)" as a different clinical category from unequivocal narcolepsy. EHS is defined clinically as having recurrent daytime sleep episodes without cataplexy. The HLA association with EHS is about 50%, which is slightly higher than normals. The HLA genes are the useful markers for the diagnosis of narcolepsy. The strong HLA association supports that narcolepsy is a disease entity. Future hopeful studies to find out the liability genes to narcolepsy include DNA studies on families with multiple narcoleptic patients. So far all family members with narcolepsy and EHS in our 4 multiplex families carried HLA DR15 and DQ6. Narcolepsy will be better understood in two groups, one major group with HLA association and another rare group without HLA association. The latter group, however, needs careful clinical diagnostic evaluation. We conclude that narcolepsy provides a very attractive tool for the genetic investigation of sleep and sleep disorders.
