title: Genetics of enteric neuropathies.
abstract: Abnormal development or disturbed functioning of the enteric nervous system (ENS), the intrinsic innervation of the gastrointestinal tract, is associated with the development of neuropathic gastrointestinal motility disorders. Here, we review the underlying molecular basis of these disorders and hypothesize that many of them have a common defective biological mechanism. Genetic burden and environmental components affecting this common mechanism are ultimately responsible for disease severity and symptom heterogeneity. We believe that they act together as the fulcrum in a seesaw balanced with harmful and protective factors, and are responsible for a continuum of symptoms ranging from neuronal hyperplasia to absence of neurons.
authors.affiliation: Department of Clinical Genetics, Erasmus University Medical Centre - Sophia Children's Hospital, Rotterdam, The Netherlands. Electronic address: e.brosens@erasmusmc.nl.
authors.forename: Erwin
authors.initials: E
authors.lastname: Brosens
authors.affiliation: Department of Clinical Genetics, Erasmus University Medical Centre - Sophia Children's Hospital, Rotterdam, The Netherlands; Stem Cells and Regenerative Medicine, Birth Defects Research Centre, UCL Institute of Child Health, London, UK.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Burns
authors.affiliation: Department of Clinical Genetics, Erasmus University Medical Centre - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Alice S
authors.initials: AS
authors.lastname: Brooks
authors.affiliation: UOC Medical Genetics, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Matera
authors.affiliation: Department of Genetics, Reproduction and Fetal Medicine, Institute of Biomedicine of Seville (IBIS), Seville, Spain; Centre for Biomedical Network Research on Rare Diseases (CIBERER), Seville, Spain.
authors.forename: Salud
authors.initials: S
authors.lastname: Borrego
authors.affiliation: UOC Medical Genetics, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Ceccherini
authors.affiliation: Division of Paediatric Surgery, Department of Surgery, Li Ka Shing Faculty of Medicine of the University of Hong Kong, Hong Kong, China.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Tam
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Centre for Reproduction, Development, and Growth, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
authors.forename: Maria-Mercè
authors.initials: MM
authors.lastname: García-Barceló
authors.affiliation: Stem Cells and Regenerative Medicine, Birth Defects Research Centre, UCL Institute of Child Health, London, UK.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Thapar
authors.affiliation: Pediatric Gastroenterology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Benninga
authors.affiliation: Department of Clinical Genetics, Erasmus University Medical Centre - Sophia Children's Hospital, Rotterdam, The Netherlands; Stem Cells and Regenerative Medicine, Birth Defects Research Centre, UCL Institute of Child Health, London, UK.
authors.forename: Robert M W
authors.initials: RM
authors.lastname: Hofstra
authors.affiliation: Department of Clinical Genetics, Erasmus University Medical Centre - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Alves
mesh_terms: D017615:Enteric Nervous System / Q000254:growth & development / Q000473:pathology*; D005769:Gastrointestinal Motility / Q000235:genetics / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000294:innervation* / Q000473:pathology*; D059647:Gene-Environment Interaction; D006627:Hirschsprung Disease / Q000235:genetics; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000502:physiology
keywords: Aganglionosis; Enteric nervous system; Enteric neuropathy; Gastrointestinal tract; Hypoganglionosis