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


CONCLUSIONS
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.
Dauvilliers
Y
Y
Neurologie B, Hôpital Gui-de-Chauliac, Montpellier, France.
Mayer
G
G
Lecendreux
M
M
Neidhart
E
E
Peraita-Adrados
R
R
Sonka
K
K
Billiard
M
M
Tafti
M
M
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D020274:Autoimmune Diseases of the Nervous System / Q000235:genetics* / Q000276:immunology* / Q000523:psychology; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D004247:DNA / Q000235:genetics; D004298:Dopamine / Q000502:physiology; D005260:Female; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006801:Humans; D017593:Kleine-Levin Syndrome / Q000235:genetics* / Q000276:immunology* / Q000523:psychology; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D017286:Polysomnography; D012701:Serotonin / Q000502:physiology; D012890:Sleep / Q000502:physiology; D014365:Tryptophan Hydroxylase / Q000378:metabolism
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D012701:Serotonin; D004247:DNA; D014365:Tryptophan Hydroxylase; D002394:Catechol O-Methyltransferase; D004298:Dopamine