The disease occurs in approximately 1 in 5000 births, making it a relatively common congenital condition.[16]Spouge D, Baird PA. Hirschsprung disease in a large birth cohort. Teratology. 1985 Oct;32(2):171-7.
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[17]Anderson JE, Vanover MA, Saadai P, et al. Epidemiology of Hirschsprung disease in California from 1995 to 2013. Pediatr Surg Int. 2018 Dec;34(12):1299-1303.
https://www.doi.org/10.1007/s00383-018-4363-9
http://www.ncbi.nlm.nih.gov/pubmed/30324568?tool=bestpractice.com
In one retrospective comparative cohort study from California, the risk was highest among African-American children (with an incidence of 4.1/10,000 births compared with 2.2/10,000 overall).[17]Anderson JE, Vanover MA, Saadai P, et al. Epidemiology of Hirschsprung disease in California from 1995 to 2013. Pediatr Surg Int. 2018 Dec;34(12):1299-1303.
https://www.doi.org/10.1007/s00383-018-4363-9
http://www.ncbi.nlm.nih.gov/pubmed/30324568?tool=bestpractice.com
Short-segment Hirschsprung disease affects boys much more frequently than girls, with a male-to-female ratio ranging from 2.8:1 to 4.0:1.[1]Montalva L, Cheng LS, Kapur R, et al. Hirschsprung disease. Nat Rev Dis Primers. 2023 Oct 12;9(1):54.
http://www.ncbi.nlm.nih.gov/pubmed/37828049?tool=bestpractice.com
Syndromic and long-segment Hirschsprung disease affects boys and girls equally.[1]Montalva L, Cheng LS, Kapur R, et al. Hirschsprung disease. Nat Rev Dis Primers. 2023 Oct 12;9(1):54.
http://www.ncbi.nlm.nih.gov/pubmed/37828049?tool=bestpractice.com
Inheritance patterns are complex; the risk for a sister of a male patient is 0.6%, whereas the risk for a brother of a female patient with long-segment disease is 18%.[18]Passarge E. The genetics of Hirschsprung's disease. Evidence for heterogeneous etiology and a study of sixty-three families. N Engl J Med. 1967;276:138-43.
http://www.ncbi.nlm.nih.gov/pubmed/4224912?tool=bestpractice.com
The majority of cases occur sporadically, typically as short-segment Hirschsprung disease with a multifactorial inheritance pattern. However, some cases are familial and are more often long-segment Hirschsprung disease or total colonic aganglionosis (TCA) with an autosomal dominant inheritance pattern.[19]Karim A, Tang CS, Tam PK. The emerging genetic landscape of Hirschsprung disease and its potential clinical applications. Front Pediatr. 2021;9:638093.
https://www.doi.org/10.3389/fped.2021.638093
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[20]Xiao J, Hao LW, Wang J, et al. Comprehensive characterization of the genetic landscape of familial Hirschsprung's disease. World J Pediatr. 2023 Jul;19(7):644-51.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10258170
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Approximately 5% to 32% of all individuals affected with the disease have an associated congenital anomaly.[21]Moore SW. The contribution of associated congenital anomalies in understanding Hirschsprung's disease. Pediatr Surg Int. 2006;22:305-15.
http://www.ncbi.nlm.nih.gov/pubmed/16518596?tool=bestpractice.com
Down syndrome is the most common association, with an overall incidence of 7.3% in children with Hirschsprung disease.[22]Friedmacher F, Puri P. Hirschsprung's disease associated with Down syndrome: a meta-analysis of incidence, functional outcomes and mortality. Pediatr Surg Int. 2013 Sep;29(9):937-46.
http://www.ncbi.nlm.nih.gov/pubmed/23943251?tool=bestpractice.com
Other associated syndromes include Shah-Waardenburg syndrome and Mowat-Wilson syndrome.[1]Montalva L, Cheng LS, Kapur R, et al. Hirschsprung disease. Nat Rev Dis Primers. 2023 Oct 12;9(1):54.
http://www.ncbi.nlm.nih.gov/pubmed/37828049?tool=bestpractice.com
[17]Anderson JE, Vanover MA, Saadai P, et al. Epidemiology of Hirschsprung disease in California from 1995 to 2013. Pediatr Surg Int. 2018 Dec;34(12):1299-1303.
https://www.doi.org/10.1007/s00383-018-4363-9
http://www.ncbi.nlm.nih.gov/pubmed/30324568?tool=bestpractice.com
[23]Moore SW. Chromosomal and related Mendelian syndromes associated with Hirschsprung's disease. Pediatr Surg Int. 2012 Nov;28(11):1045-58.
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[24]Amiel J, Sproat-Emison E, Garcia-Barcelo M, et al. Hirschsprung disease, associated syndromes and genetics: a review. J Med Genet. 2008 Jan;45(1):1-14.
https://www.doi.org/10.1136/jmg.2007.053959
http://www.ncbi.nlm.nih.gov/pubmed/17965226?tool=bestpractice.com
Anorectal malformations are rarely associated with the disease; approximately 2% of children with anorectal malformation also had Hirschsprung disease in one systematic review.[25]Hofmann AD, Puri P. Association of Hirschsprung's disease and anorectal malformation: a systematic review. Pediatr Surg Int. 2013 Sep;29(9):913-7.
https://pubmed.ncbi.nlm.nih.gov/23948812
http://www.ncbi.nlm.nih.gov/pubmed/23948812?tool=bestpractice.com