SNP Shot: Genomic Insights

Hirschsprung disease is a condition affecting the intestines, characterized by the absence of nerve cells in certain sections. This nerve absence stems from improper nerve development (enteric nerves) in the intestine during fetal development, before birth. While often diagnosed within the first two months of life, milder cases might be identified later in childhood.

The enteric nerves are crucial for triggering muscle contractions that propel stool through the intestine. In Hirschsprung disease, the lack of these nerves in affected areas prevents this movement, leading to severe constipation or a complete blockage of the intestine. Other symptoms can include vomiting, abdominal pain or bloating, diarrhea, difficulty feeding, malnutrition, and impaired growth. Individuals with this disorder face an increased risk of serious complications like intestinal inflammation (enterocolitis) or a tear in the intestinal wall (intestinal perforation), which can lead to life-threatening infections.

Hirschsprung disease is classified into two primary types: short-segment disease and long-segment disease, based on the extent of the intestine lacking nerve cells. In short-segment disease, the nerve cell absence is limited to the final section of the large intestine (colon). This is the more prevalent form, accounting for approximately 80% of Hirschsprung disease cases. Interestingly, short-segment disease is about four times more common in males than females, although the reasons for this are unknown. Long-segment disease involves a larger portion of the large intestine lacking nerve cells and represents the more severe form. It affects approximately 20% of individuals with Hirschsprung disease and occurs equally in males and females. In rare instances, the entire large intestine may be affected (total colonic aganglionosis), or even the entire large and small intestine (total intestinal aganglionosis) may lack nerve cells.

Hirschsprung disease can sometimes occur alongside other conditions, such as Waardenburg syndrome type IV, Mowat-Wilson syndrome, or congenital central hypoventilation syndrome. These instances are classified as syndromic. Alternatively, Hirschsprung disease can occur on its own, without the presence of other conditions, and these cases are classified as isolated or nonsyndromic.

Inheritance:

About 20% of Hirschsprung disease cases appear in multiple family members. The remaining cases are found in individuals with no family history of the disorder. Hirschsprung disease often exhibits a dominant inheritance pattern, meaning that a single copy of an altered gene in each cell may be enough to cause the condition. The inheritance pattern is considered to have incomplete penetrance, which means that not everyone who inherits the altered gene will develop Hirschsprung disease.