Some of these occur in an autosomal dominant manner. The cause of the remaining cases is unclear. If otherwise normal parents have one child with the condition, the next child has a 4% risk of being affected. Genetics
Several genes and specific regions on chromosomes (loci) have been shown or suggested to be associated with Hirschsprungs disease:
The RET proto-oncogene accounts for the highest proportion of both familial and sporadic cases, with a wide range of mutations scattered along its entire coding region. A proto-oncogene  can cause cancer if it is mutated or overexpressed. RET proto-oncogene
RET is a gene that codes for proteins that assist cells of the neural crest in their movement through the digestive tract during the development of the embryo. Those neural crest cells eventually form bundles of nerve cells called ganglions. EDNRB codes for proteins that connect these nerve cells to the digestive tract. Thus, mutations in these two genes could directly lead to the absence of certain nerve fibers in the colon. Research suggests that several genes are associated with Hirschsprungs disease. Also, new research suggests that mutations in genomic sequences involved in regulating EDNRB have a bigger impact on Hirschsprungs disease than previously thought.RET can mutate in many ways and is associated with Down syndrome. Since Down syndrome is comorbid in 2% of Hirschsprungs cases, a likelihood exists that RET is involved heavily in both Hirschsprungs disease and Down syndrome. RET is also associated with medullary thyroid cancer and neuroblastoma, which is a type of cancer common in children.
Hirschsprungs disease (HD or HSCR) is a birth defect in which nerves are missing from parts of the intestine. The most prominent symptom is constipation. Other symptoms may include vomiting, abdominal pain, diarrhea and slow growth. Symptoms usually become apparent in the first two months of life. Complications may include enterocolitis, megacolon, bowel obstruction and intestinal perforation.The disorder may occur by itself or in association with other genetic disorders such as Down syndrome or Waardenburg syndrome. About half of isolated cases are linked to a specific genetic mutation, and about 20% occur within families. Some of these occur in an autosomal dominant manner. The cause of the remaining cases is unclear. If otherwise normal parents have one child with the condition, the next child has a 4% risk of being affected. The condition is divided into two main types, short-segment and long-segment, depending on how much of the bowel is affected. Rarely, the small bowel may be affected, as well. Diagnosis is based on symptoms and confirmed by biopsy.Treatment is generally by surgery to remove the affected section of bowel. The surgical procedure most often carried out is known as a "pull through". Occasionally, an intestinal transplantation may be recommended. Hirschsprungs disease occurs in about one in 5,000 of newborns. Males are more often affected than females. The condition is believed to have first been described in 1691 by Dutch anatomist Frederik Ruysch and is named after Danish physician Harald Hirschsprung following his description in 1888.