Kleine-Levin syndrome: an autoimmune hypothesis based on clinical and genetic analyses

Neurology. 2002 Dec 10;59(11):1739-45. doi: 10.1212/01.wnl.0000036605.89977.d0.


Background: Kleine-Levin syndrome (KLS) is a rare disorder of unknown etiology. Pathophysiologic hypotheses include a hypothalamic dysfunction and abnormalities in the central serotonin and dopamine metabolism. Several clinical symptoms also suggest an underlying autoimmune process.

Objective: To systematically investigate patients with KLS with reference to the available hypotheses.

Methods: The authors collected clinical, polysomnographic, CSF, CT, and MRI records and analyzed gene polymorphisms of HLA-DQB1, tryptophan hydroxylase (TpH), and catechol-O-methyltransferase (COMT) in 30 unrelated patients with KLS and their families. The genotype data were contrasted with data from a normal control population.

Results: Only human leukocyte antigen (HLA)-DQB1*0201 allele frequency was significantly increased in patients with KLS. Three patients with KLS but none of the control subjects were DQB1*0201 homozygous. Two affected subjects from the same family were DQB1*0201 homozygous. In 17 DQB1*0201 heterozygous parents, 11 (64.7%) had transmitted this allele, suggesting a preferential transmission.

Conclusion: These findings, together with the young age at onset, the recurrence of symptoms, and the frequent infectious precipitating factors, suggest an autoimmune etiology for Kleine-Levin syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Autoimmune Diseases of the Nervous System / genetics*
  • Autoimmune Diseases of the Nervous System / immunology*
  • Autoimmune Diseases of the Nervous System / psychology
  • Catechol O-Methyltransferase / metabolism
  • DNA / genetics
  • Dopamine / physiology
  • Female
  • Genotype
  • HLA-DQ Antigens / genetics
  • HLA-DQ beta-Chains
  • Humans
  • Kleine-Levin Syndrome / genetics*
  • Kleine-Levin Syndrome / immunology*
  • Kleine-Levin Syndrome / psychology
  • Male
  • Phenotype
  • Polymorphism, Genetic / genetics
  • Polysomnography
  • Serotonin / physiology
  • Sleep / physiology
  • Tryptophan Hydroxylase / metabolism


  • HLA-DQ Antigens
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • Serotonin
  • DNA
  • Tryptophan Hydroxylase
  • Catechol O-Methyltransferase
  • Dopamine