title: Hirschsprung disease, associated syndromes and genetics: a review.
abstract: Hirschsprung disease (HSCR, aganglionic megacolon) represents the main genetic cause of functional intestinal obstruction with an incidence of 1/5000 live births. This developmental disorder is a neurocristopathy and is characterised by the absence of the enteric ganglia along a variable length of the intestine. In the last decades, the development of surgical approaches has importantly decreased mortality and morbidity which allowed the emergence of familial cases. Isolated HSCR appears to be a non-Mendelian malformation with low, sex-dependent penetrance, and variable expression according to the length of the aganglionic segment. While all Mendelian modes of inheritance have been described in syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. The tyrosine kinase receptor RET is the major gene with both rare coding sequence mutations and/or a frequent variant located in an enhancer element predisposing to the disease. Hitherto, 10 genes and five loci have been found to be involved in HSCR development.
authors.affiliation: Université Paris 5-Descartes, Faculté de Médecine, INSERM U-781, AP-HP, Hôpital Necker-Enfant Malades, Paris, France. amiel@necker.fr
authors.forename: J
authors.initials: J
authors.lastname: Amiel
authors.forename: E
authors.initials: E
authors.lastname: Sproat-Emison
authors.forename: M
authors.initials: M
authors.lastname: Garcia-Barcelo
authors.forename: F
authors.initials: F
authors.lastname: Lantieri
authors.forename: G
authors.initials: G
authors.lastname: Burzynski
authors.forename: S
authors.initials: S
authors.lastname: Borrego
authors.forename: A
authors.initials: A
authors.lastname: Pelet
authors.forename: S
authors.initials: S
authors.lastname: Arnold
authors.forename: X
authors.initials: X
authors.lastname: Miao
authors.forename: P
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authors.lastname: Griseri
authors.forename: A S
authors.initials: AS
authors.lastname: Brooks
authors.forename: G
authors.initials: G
authors.lastname: Antinolo
authors.forename: L
authors.initials: L
authors.lastname: de Pontual
authors.forename: M
authors.initials: M
authors.lastname: Clement-Ziza
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: C
authors.initials: C
authors.lastname: Kashuk
authors.forename: K
authors.initials: K
authors.lastname: West
authors.forename: K K-Y
authors.initials: KK
authors.lastname: Wong
authors.forename: S
authors.initials: S
authors.lastname: Lyonnet
authors.forename: A
authors.initials: A
authors.lastname: Chakravarti
authors.forename: P K-H
authors.initials: PK
authors.lastname: Tam
authors.forename: I
authors.initials: I
authors.lastname: Ceccherini
authors.forename: R M W
authors.initials: RM
authors.lastname: Hofstra
authors.forename: R
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authors.lastname: Fernandez
mesh_terms: D002869:Chromosome Aberrations; D005260:Female; D006627:Hirschsprung Disease / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D007415:Intestinal Obstruction / Q000235:genetics; D008297:Male; D008967:Molecular Biology; D009154:Mutation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D013577:Syndrome
chemical_list: D020794:Receptor Protein-Tyrosine Kinases