New mutations associated with Hirschsprung disease

Introduction: Hirschsprung disease is caused by an impairment in cell migration from the neural crest to the gastrointestinal tract, resulting in an absence of neurons in the myenteric plexus. Many mutations in several genes have been associated to Hirschsprung disease; most of them affecting the RET proto-oncogen pathway. The purpose of this study is the description of novel and known mutations in genes associated to Hirschsprung disease and their prognostic implications. Material and methods: Retrospective analysis of patients with Hirschsprung disease and positive genetic studies evaluated from 1970 to 2013. Results: We found 21 positive genetic studies in the global series, 17 of them involving the RET proto-oncogene. Two of the mutations are novel and they have not been reported in the medical literature. Conclusions: The RET protooncogene is the main gene associated with Hirschsprung disease. There are still multiple unknown mutations related to the pathogenesis of the disease. The study of this gene must be part of the work-up of all patients with Hirschsprung disease, as well as their first degree relatives if the mutation is associated with MEN2A and MEN2B syndromes.