The disorder described by Hirschsprung (1888) and known as Hirschsprung disease or aganglionic megacolon is characterized by congenital absence of intrinsic ganglion cells in the myenteric (Auerbach) and submucosal (Meissner) plexuses of the gastrointestinal tract. Patients are diagnosed ... The disorder described by Hirschsprung (1888) and known as Hirschsprung disease or aganglionic megacolon is characterized by congenital absence of intrinsic ganglion cells in the myenteric (Auerbach) and submucosal (Meissner) 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. Total colonic aganglionosis and total intestinal HSCR also occur (Amiel et al., 2008). Isolated HSCR appears to be of complex nonmendelian inheritance with low sex-dependent penetrance and variable expression according to the length of the aganglionic segment, suggestive of the involvement of one or more genes with low penetrance (Amiel et al., 2008). For a general description and a discussion of genetic heterogeneity of Hirschsprung disease (HSCR), see 142623.
Puffenberger et al. (1992) found a high frequency of Hirschsprung disease in an extended inbred Mennonite kindred. In 49 nuclear families, 56 affected persons were found. In one of these individuals, one or more of the following characteristics ... Puffenberger et al. (1992) found a high frequency of Hirschsprung disease in an extended inbred Mennonite kindred. In 49 nuclear families, 56 affected persons were found. In one of these individuals, one or more of the following characteristics was found: white forelock, hearing deficit, and heterochromia iridis. However, further studies suggested that this triad of traits segregated independently of Hirschsprung disease in several of the families within the kindred. A couple who immigrated to the United States about 1717 was ancestral to both parents of all affected individuals. Segregation analysis yielded a segregation ratio of 12.0% for males and 6.2% for females.
Puffenberger et al. (1994) studied the endothelin-B receptor gene (EDNRB; 131244), which maps to the same area of chromosome 13 as does the Mennonite Hirschsprung disease, and found point mutations.
Shanske et al. (2001) reviewed 10 ... Puffenberger et al. (1994) studied the endothelin-B receptor gene (EDNRB; 131244), which maps to the same area of chromosome 13 as does the Mennonite Hirschsprung disease, and found point mutations. Shanske et al. (2001) reviewed 10 case reports of patients with 13q deletions and Hirschsprung disease or other intestinal anomalies, and added an eleventh case.