This report described 'Hirschsprung disease, susceptibility to, 1' (HSCR1); HSCR1 exhibits autosomal dominant inheritance. The human gene implicated in this disease is RET, which encodes a receptor tyrosine kinase. For experiments done in flies relevant to HSCR1, see the human disease model report 'intestinal dysfunction, RET-related' (FBhh0000995).
The human gene RET is implicated in multiple other diseases, including several types of cancer; see MIM:164761.
[updated Mar. 2019 by FlyBase; FBrf0222196]
[HIRSCHSPRUNG DISEASE, SUSCEPTIBILITY TO, 1; HSCR1](https://omim.org/entry/142623)
[RET PROTOONCOGENE; RET](https://omim.org/entry/164761)
Hirschsprung disease has been observed in association with MEN2A (Verdy et al., 1982; pubmed:6136579) and gastrointestinal symptoms are a significant component of MEN2B (Mahaffey et al., 1990; pubmed:1967641), both of which are caused by mutation in the RET gene. [from MIM:142623; 2019.03.25]
The disorder known as Hirschsprung disease or aganglionic megacolon is characterized by congenital absence of intrinsic ganglion cells in the myenteric and submucosal plexuses of the gastrointestinal tract. Patients are diagnosed with the short-segment form (S-HSCR, approximately 80% of cases) when the aganglionic segment does not extend beyond the upper sigmoid, and with the long-segment form (L-HSCR) when aganglionosis extends proximal to the sigmoid (Amiel et al., 2008; pubmed:17965226). Total colonic aganglionosis and total intestinal HSCR also occur. [from MIM:142623; 2019.03.25]
Aganglionic megacolon may occur in a large number of other disorders, including Down syndrome. [from MIM:142623; 2019.03.25]
Because they could not demonstrate simple mendelian inheritance in their series of Hirschsprung disease as a whole, Bodian and Carter (1963, Ann. Hum. Genet. 26: 261-277) concluded that Hirschsprung disease is probably multifactorial (polygenic) in its causation. [from MIM:142623; 2019.03.25]
Susceptibility to Hirschsprung disease 1 (HSCR1) is associated with variation in the RET gene; familial forms exhibit autosomal dominant inheritance. [from MIM:142623; 2019.03.25]
