Hirschsprung disease
Hirschsprung disease is an intestinal disorder caused by the absence of nerve cells in parts of the bowel, leading to severe constipation or intestinal blockage.
Overview
Hirschsprung disease is an intestinal disorder characterized by the absence of nerves in parts of the intestine. This condition occurs when the nerves in the intestine (enteric nerves) do not form properly during embryonic development. This condition is usually identified in the first two months of life, although less severe cases may be diagnosed later in childhood.
Enteric nerves trigger the muscle contractions that move stool through the intestine. Without these nerves, material cannot be pushed through, causing severe constipation or complete blockage. Other signs and symptoms include vomiting, abdominal pain or swelling, diarrhea, poor feeding, malnutrition, and slow growth. People with this disorder are at risk of developing more serious conditions such as inflammation of the intestine (enterocolitis) or a hole in the wall of the intestine (intestinal perforation).
Types
- Short-segment disease: Nerve cells are missing from only the last segment of the large intestine (colon). This is the most common type, occurring in approximately 80 percent of cases.
- Long-segment disease: Nerve cells are missing from most of the large intestine. This occurs in approximately 20 percent of cases and is more severe.
Frequency
Hirschsprung disease occurs in approximately 1 in 5,000 newborns.
Causes
Isolated Hirschsprung disease can result from mutations in one of several genes, including the RET, EDNRB, and EDN3 genes. The genetics of this condition are complex; while a single gene mutation can cause the condition, mutations in multiple genes may be required in some cases. The genetic cause is unknown in approximately half of affected individuals.
The RET gene is the most common known genetic cause. It provides instructions for a protein essential for the normal development of enteric nerves. Mutations result in a nonfunctional protein, preventing normal nerve development. The EDNRB and EDN3 genes are also critical for the formation of these nerves; changes in these genes disrupt signaling processes necessary for nerve development.
Genes Associated with Hirschsprung Disease
- EDN3
- EDNRB
- RET
- SOX10
Inheritance
Approximately 20 percent of cases occur in multiple members of the same family. The condition appears to have a complex inheritance pattern, often described as having incomplete penetrance, meaning not everyone who inherits an altered gene develops the disorder.
Other Names for This Condition
- Aganglionic megacolon
- Congenital intestinal aganglionosis
- Congenital megacolon
- Hirschsprung's disease
- HSCR