Clinical, polysomnographic, CSF, CT, and MRI records and genotype data of 30 unrelated patients with Kleine-Levin syndrome (KLS) and their families were studied at Hopital Gui-de-Chauliac, Montpellier, France, and other sleep centers. The sex ratio showed a predominance of males (25/5). The mean age at onset was 15 +/- 3 years. The mean number of episodes per year was 4 +/- 3 and the mean duration of episodes was 12 +/- 8 days. Viral upper respiratory tract infection was a precipitating factor in 16/23 (70%). The two essential diagnostic criteria, recurrent hypersomnia with asssociated cognitive and mood disturbances, were present in all patients. Hyperphagia occurred in 17 (57%), and hypersexuality in 14 (47%) patients. Brain imaging and CSF were normal. EEGs were not recorded. Treatment for hypersomnia that was partially effective included the stimulant, modafinil, carbamazepine, and lithium. Neuroleptics were ineffective. The genotype data analysis of KLS patients, contrasted with normal controls, found a significant increase in the frequency of human leukocyte antigen (HLA)-DQB1*0201 allele, and 3 patients with KLS were homozygous for DQB1*0201, 2 from the same family. An autoimmune etiology is suggested. [1]

COMMENT. The etiology of Kleine-Levin syndrome is unknown. Periodic hypothalamic dysfunction, focal encephalitis, and an autoimmune process are possibilities. The disorder is rarely familial, only in 2 of 30 patients in the above study, and in 2 siblings in the following report. Levels of CSF orexin (hypocretin), decreased in some narcoleptic patients, were normal in the following familial cases.

Familial Kleine-Levin syndrome is reported in 2 siblings with unusually long hypersomnic spells, from Tufts University, Boston, MA [2]. Both patients shared the HLA-DR2, DQ1, and DR5 haplotypes. Treatment with lithium, methylphenidate, modafinil, clonazepam, and other drugs was ineffective in preventing or reducing the duration of hypersomnic spells. Patient 1, a 15-year-old boy, developed flu-like symptoms without fever, he slept excessively for 9 days, and was irritable when awake. Eight similar attacks occurred during the following 10 months, and 16 hypersomnic spells in 5 years. Compulsive symptoms followed the episodes. Patient 2, the sister of patient 1, began having hypersomnic spells at age 13 years, the first preceded by a flu-like illness. Between attacks, MRI, EEG, Ebstein-Barr virus titer, ESR, and CSF were normal.