Disorder
Hirschsprung disease, susceptibility to
Clinical Characteristics
General description (for patients):
Hirschsprung disease is a congenital intestinal disease in which the innervation is abnormal. The result is abnormal bowel constrictions, especially in the colon, leading to constipation and sometimes serious blockage which, if not treated, can lead to infections and rupture of the intestines. Discomfort, vomiting and a swollen abdomen are common. It is often evident at birth when infants aren’t able to have bowel movements.
Medical description (for healthcare providers):
Aganglionic colon can be a heritable or a sporadic condition. The distal colon is most commonly involved but the disease may be more extensive. Discomfort can be significant but the major health risk is obstructive enterocolitis and bowel perforation. More mildly affected individuals may suffer life-long constipation. Anemia from malabsorption can be a secondary problem. Surgery can restore a normal lifestyle.
Genetics:
This form of aganglionic colon disease is secondary to a mutation in the gene encoding the endothelin-B receptor (EDNRB) located on chromosome 13 (13q22). A 828G>T missense mutation was identified in a large Mennonite kindred in Eastern Pennsylvania. On the basis that all 122 parents descended from a single ancestral couple, and the fact that only three families had parent-to–child transmission, it was concluded that this disease was an autosomal recessive. The segregation ratios are not as predicted though, suggesting that this is a susceptibility mutation, with 74% of homozygotes and 21% of heterozygotes having clinical disease. A significant proportion of cases also had sensorineural hearing loss and pigmentary anomalies including hypopigmentation, white forelocks, and bicolored irides suggesting the Waardenburg-Shah syndrome (#277580). Hirschsprung’s disease seems to be multigenic since other modes of inheritance involving more mutations at other loci are also known. Many cases occur sporadically (see #142623).
Management:
The usual laxatives and stool softeners are ineffective and surgery to connect functioning segments may be required to restore nearly normal lifestyles.
Diet modifications as needed to reduce discomfort.
Prognosis:
Excellent
Specialists and specialty centers:
Surgeon, Gastroenterologist, Nutritionist.
References:
Puffenberger, E.G., Kauffman, E.R., Bolk, S., Matise, T.C., Washington, S.S., Angrist, M., Weissenbach, J., Garver, K.L., Mascari, M., Ladda, R., Slaugenhaupt, S.A., and Chakravarti, A.: Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22. Hum. Mol. Genet. 3: 1217-1225, 1994. PubMed ID: 7987295
Puffenberger, E.G., Hosoda, K., Washington, S.S., Nakao, K., deWit, D., Yanagisawa, M., and Chakravarti, A.: A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung’s disease. Cell 79: 1257-1266, 1994. PubMed ID: 8001158
Kessmann, J.: Hirschsprung’s disease: diagnosis and management. Am. Fam. Physician 74: 1319-1322, 1327-1328, 2006. PubMed ID: 17087425
Amiel, J. and Lyonnet, S.: Hirschsprung disease, associated syndromes, and genetics: a review. J. Med. Genet. 38: 729-739, 2001. PubMed ID: 11694544
View A - Z