Understanding the causes of Hirschsprung’s disease begins with knowing it is present at birth. This disorder starts early in pregnancy when nerve cells do not finish their normal movement through the bowel. These cells, called ganglion cells, control the bowel muscles that push stool forward. When this process fails, part of the bowel cannot relax, causing a blockage. The main causes of Hirschsprung’s disease are genetic changes and problems during early growth in the womb. The severity can vary in each child.
How the Problem Starts
The bowel nerves form between weeks five and twelve of pregnancy. Special cells from the neural crest move into the gut wall and become ganglion cells. These cells allow peristalsis, the wave-like motion that moves food through the gut. In Hirschsprung’s disease, this movement stops too soon. Parts of the colon or sometimes the small bowel do not get nerve cells. These areas stay tight and block stool. Waste and gas then build up above the blockage.
Role of Genes
The main reason for this failure is genetic. The RET gene is the most common cause. It makes a protein that helps nerve cells grow. Other important genes include EDNRB, EDN3, GDNF, and SOX10. These work together in a complex system. A change in one or more of them can stop nerve growth in the bowel.
The condition can run in families. In some cases, it appears by chance. If there is a family history, the risk for siblings is higher. The inheritance pattern may be dominant or recessive, depending on the gene and the length of bowel affected. Longer bowel segments often run more strongly in families. Boys get short-segment disease more often than girls. Long-segment disease affects both sexes equally.
Links with Genetic Syndromes
Hirschsprung’s disease can also occur with chromosomal problems. Down syndrome is the most common. Up to 10% of children with Hirschsprung’s also have Down syndrome. Other linked conditions include Waardenburg syndrome, Mowat-Wilson syndrome, and CCHS (congenital central hypoventilation syndrome). These links show how nerve development issues play a key role in this disease.
Do Environment or Pregnancy Factors Matter?
Environmental factors do not seem to cause Hirschsprung’s disease. However, doctors believe that unknown changes in the womb or gene activity might play a small role. No strong link has been found with a mother’s diet, lifestyle, or infections during pregnancy. This makes the condition very different from other birth defects caused by outside factors.
How Much of the Bowel Is Affected?
The length of bowel without nerve cells varies. In most children (about 80%), only a short part of the rectum or sigmoid colon is involved. In 15–20%, the disease goes higher in the colon. Rarely, it affects the whole colon or even the small bowel. These severe forms usually appear soon after birth and often link to family history or other syndromes.
Why Understanding the Causes Helps
Research continues on the causes of Hirschsprung’s disease. Genetic studies now make diagnosis and family risk checks easier. Testing can help families plan early care and future pregnancies.
In short, the causes of Hirschsprung’s disease come from early nerve growth problems in the bowel. These mainly result from gene changes in RET and other key genes. They sometimes occur with chromosomal syndromes. So far, no clear environmental risk is known. Learning these causes helps doctors give better advice, plan care, and improve outcomes for families.
