PURPOSE: Formal studies of the genetics of enuresis have been performed since the 1930s and molecular genetics since 1995, both highlighting the importance of hereditary factors in the etiology of nocturnal enuresis. We summarize the current state of knowledge with respect to the genetics of nocturnal enuresis and its genotype-phenotype interactions. MATERIALS AND METHODS: A comprehensive review of the published data available on the genetic basis of enuresis was performed. RESULTS: Genetic factors are the most important in the etiology of nocturnal enuresis but somatic and psychosocial environmental factors have a major modulatory effect. Most commonly, nocturnal enuresis is inherited via an autosomal dominant mode of transmission with high penetrance (90%). However, a third of all cases are sporadic, and the difference between sporadic and familial forms is not known. Four gene loci associated with nocturnal enuresis have been identified but the existence of others is presumed (locus heterogeneity). All likely candidate genes have been excluded so far. There is no specific association among the different loci, type of wetting and other aspects of the phenotype. All subtypes of nocturnal enuresis (primary, secondary, combined day/night wetting) are susceptible to comparable genetic influences. Certain syndromes of day wetting follow their own genetic mechanisms but this association with the genetics of nocturnal enuresis is not known. CONCLUSIONS: Nocturnal enuresis is a common, genetic and heterogeneous disorder. The associations between genotype and phenotype are complex and are susceptible to environmental influences. Therefore, exact assessment of the clinical phenotype and identification of intermediary phenotypes or traits are needed. Future research will focus on the identification of genes, gene products and their interaction with environmental factors.
PURPOSE: Formal studies of the genetics of enuresis have been performed since the 1930s and molecular genetics since 1995, both highlighting the importance of hereditary factors in the etiology of nocturnal enuresis. We summarize the current state of knowledge with respect to the genetics of nocturnal enuresis and its genotype-phenotype interactions. MATERIALS AND METHODS: A comprehensive review of the published data available on the genetic basis of enuresis was performed. RESULTS: Genetic factors are the most important in the etiology of nocturnal enuresis but somatic and psychosocial environmental factors have a major modulatory effect. Most commonly, nocturnal enuresis is inherited via an autosomal dominant mode of transmission with high penetrance (90%). However, a third of all cases are sporadic, and the difference between sporadic and familial forms is not known. Four gene loci associated with nocturnal enuresis have been identified but the existence of others is presumed (locus heterogeneity). All likely candidate genes have been excluded so far. There is no specific association among the different loci, type of wetting and other aspects of the phenotype. All subtypes of nocturnal enuresis (primary, secondary, combined day/night wetting) are susceptible to comparable genetic influences. Certain syndromes of day wetting follow their own genetic mechanisms but this association with the genetics of nocturnal enuresis is not known. CONCLUSIONS:Nocturnal enuresis is a common, genetic and heterogeneous disorder. The associations between genotype and phenotype are complex and are susceptible to environmental influences. Therefore, exact assessment of the clinical phenotype and identification of intermediary phenotypes or traits are needed. Future research will focus on the identification of genes, gene products and their interaction with environmental factors.
Authors: Thomas M Hyde; Amy Deep-Soboslay; Bianca Iglesias; Joseph H Callicott; James M Gold; Andreas Meyer-Lindenberg; Robyn A Honea; Llewellyn B Bigelow; Michael F Egan; Esther M Emsellem; Daniel R Weinberger Journal: Brain Date: 2008-07-31 Impact factor: 13.501