title: Familial Kleine-Levin Syndrome: A Specific Entity?
abstract: Kleine-Levin syndrome (KLS) is a rare, mostly sporadic disorder, characterized by intermittent episodes of hypersomnia plus cognitive and behavior disorders. Although its cause is unknown, multiplex families have been described. We contrasted the clinical and biological features of familial versus sporadic KLS.
  
  
  
  Two samples of patients with KLS from the United States and France (n = 260) were studied using clinical interviews and human leukocyte antigen (HLA) genotyping. A multiplex family contained two or more first- or second-degree affected relatives (familial cases).
  
  
  
  Twenty-one patients from 10 multiplex families (siblings: n = 12, including two pairs of monozygotic twins; parent-child: n = 4; cousins: n = 2; uncle-nephews: n = 3) and 239 patients with sporadic KLS were identified, yielding to 4% multiplex families and 8% familial cases. The simplex and multiplex families did not differ for autoimmune, neurological, and psychiatric disorders. Age, sex ratio, ethnicity, HLA typing, karyotyping, disease course, frequency, and duration of KLS episodes did not differ between groups. Episodes were less frequent in familial versus sporadic KLS (2.3 ± 1.8/y versus 3.8 ± 3.7/y, P = 0.004). Menses triggered more frequently KLS onset in the nine girls with familial KLS (relative risk, RR = 4.12, P = 0.03), but not subsequent episodes. Familial cases had less disinhibited speech (RR = 3.44, P = 0.049), less combined hypophagia/hyperphagia (RR = 4.38, P = 0.006), more abrupt termination of episodes (RR = 1.45, P = 0.04) and less postepisode insomnia (RR = 2.16, P = 0.008). There was similar HLA DQB1 distribution in familial versus sporadic cases and no abnormal karyotypes.
  
  
  
  Familial KLS is mostly present in the same generation, and is clinically similar to but slightly less severe than sporadic KLS.
authors.affiliation: National Reference Center for Narcolepsy, Idiopathic Hypersomnia and Kleine-Levin Syndrome, Sleep Disorders Unit and Hospital-University Institute of Neuroscience, Pitié-Salpêtrière Hospital (APHP), Pierre and Marie Curie University, Paris, France.
authors.forename: Quang Tuan Remy
authors.initials: QT
authors.lastname: Nguyen
authors.affiliation: National Reference Center for Narcolepsy, Idiopathic Hypersomnia and Kleine-Levin Syndrome, Sleep Disorders Unit and Hospital-University Institute of Neuroscience, Pitié-Salpêtrière Hospital (APHP), Pierre and Marie Curie University, Paris, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Groos
authors.affiliation: Regional Competence Center for Narcolepsy, Idiopathic Hypersomnia and Kleine-Levin Syndrome, Laennec University Hospital, Nantes, France.
authors.forename: Laurène
authors.initials: L
authors.lastname: Leclair-Visonneau
authors.affiliation: Regional Competence Center for Narcolepsy, Idiopathic Hypersomnia and Kleine-Levin Syndrome, Salengro University Hospital, Lille, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Monaca-Charley
authors.affiliation: Center for Sleep Sciences and Medicine, Stanford University, Palo Alto, CA.
authors.forename: Tom
authors.initials: T
authors.lastname: Rico
authors.affiliation: Kleine-Levin Syndrome Foundation, Boston, MA.
authors.forename: Neal
authors.initials: N
authors.lastname: Farber
authors.affiliation: Center for Sleep Sciences and Medicine, Stanford University, Palo Alto, CA.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mignot
authors.affiliation: National Reference Center for Narcolepsy, Idiopathic Hypersomnia and Kleine-Levin Syndrome, Sleep Disorders Unit and Hospital-University Institute of Neuroscience, Pitié-Salpêtrière Hospital (APHP), Pierre and Marie Curie University, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Arnulf
mesh_terms: D006970:Disorders of Excessive Somnolence / Q000150:complications / Q000235:genetics; D005192:Family Health; D005260:Female; D005602:France; D005838:Genotype; D006650:Histocompatibility Testing; D006801:Humans; D006963:Hyperphagia / Q000150:complications / Q000235:genetics; D017593:Kleine-Levin Syndrome / Q000145:classification* / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D010375:Pedigree; D035583:Rare Diseases / Q000150:complications / Q000235:genetics / Q000503:physiopathology; D007319:Sleep Initiation and Maintenance Disorders / Q000150:complications / Q000235:genetics; D014481:United States; D055815:Young Adult
keywords: Kleine-Levin syndrome; family; hypersomnia; multiplex; periodic