Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the <i>TRANK1</i> gene loci
Aditya Ambati, Ryan P. Hillary, Smaranda Leu‐Semenescu, Hanna M. Ollila, Ling Lin, Emmanuel During, Neal Farber, T. Rico, Juliette Faraco, Eileen Leary, Andrea Goldstein‐Piekarski, Yu‐Shu Huang, Fang Han, Yakov Sivan, Michel Lecendreux, Pauline Dodet, Makoto Honda, Natan Gadoth, Soňa Nevšímalová, Fabio Pizza, Takashi Kanbayashi, Rosa Peraita‐Adrados, Guy D. Leschziner, Rosa Hasan, Francesca Cañellas, Kazuhiko Kume, Makrina Daniilidou, Patrice Bourgin, David B. Rye, José L. Vicário, Birgit Högl, Seung Chul Hong, Giuseppe Plazzi, Geert Mayer, Anne Marie Landtblom, Yves Dauvilliers, Isabelle Arnulf, Emmanuel Mignot
Abstract
Significance Genetic markers in TRANK1 gene and its vicinity have been weakly associated with bipolar disorder and schizophrenia (10% increased risk). We found that the same polymorphisms are associated with Kleine-Levin syndrome (50% increased risk), a rare sleep disorder characterized by recurrent episodes of severe hypersomnia and cognitive abnormalities. Response to lithium treatment is suggestive of a pathophysiological overlap between KLS and bipolar disorder. The study also shows that variants in the TRANK1 gene region may predispose to KLS when patients have had a difficult birth, suggesting that TRANK1 gene region modulates newborns’ response to brain injury, with consequences for mental and neurological health in adulthood. Another possibility may be that the polymorphism impacts birth and KLS.