title: Smith-Magenis syndrome and its circadian influence on development, behavior, and obesity - own experience.
abstract: Smith-Magenis syndrome (SMS) is a complex genetic disorder characterized by sleep disturbance, multiple developmental anomalies, psychiatric behavior, and obesity. It is caused by a heterozygous 17p11.2 microdeletion containing the retinoic acid-induced 1 (RAI1) gene or mutation within RAI1. Sleep disorder is one of the most penetrant features of SMS. Molecular genetic studies indicate that RAI1 regulates circadian rhythm genes and when haploinsucient, causes a distorted molecular circadian network that may be the cause of the sleep disturbance and the inverted rhythm of melatonin present in most individuals with SMS. RAI1 also regulates genes involved in development, neurobehavior, and lipid metabolism. Sleep debt, daytime melatonin secretion, and environmental stress often contribute to negative behavior in persons with SMS, and food entrained circadian rhythm also influences food intake behavior and humoral signals, which also affect development and neurobehavior. The cross-talk between circadian rhythm, development, metabolism and behaviors affect the multiple phenotypic outcomes in Smith-Magenis syndrome. These findings shed light on possible effective and personalized drug treatments for SMS patients in the future.
authors.affiliation: Department of Cellular and Genetic Medicine, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Sureni V
authors.initials: SV
authors.lastname: Mullegama
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Alaimo
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Elsea
mesh_terms: D002648:Child; D002657:Child Development; D002940:Circadian Rhythm / Q000235:genetics*; D018479:Early Intervention, Educational / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D009765:Obesity / Q000503:physiopathology; D010641:Phenotype; D057285:Precision Medicine / Q000379:methods; D058496:Smith-Magenis Syndrome / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology*