Hirschsprung's Disease

Hirschsprung's disease (HD), also known as aganglionic megacolon or congenital intestinal aganglionosis, is a congenital condition characterised by the absence of nerve cells (ganglia) in parts of the intestine. This defect leads to severe constipation and other gastrointestinal issues.

Signs and Symptoms

Typically diagnosed shortly after birth, Hirschsprung's disease manifests through various symptoms. Newborns often fail to pass their first stool (meconium) within 48 hours, and present with a swollen belly, vomiting, and flatulence. In older children, symptoms may include chronic constipation, abdominal distension, fatigue, and failure to thrive.

Associated Syndromes

Hirschsprung's disease can also be part of multi-system disorders such as:

• Bardet–Biedl syndrome
• Cartilage–hair hypoplasia
• Congenital central hypoventilation syndrome
• MEN2
• Mowat–Wilson syndrome
• Smith–Lemli–Opitz syndrome
• Trisomy 21 (Down syndrome)
• Some forms of Waardenburg syndrome

Cause

The disorder can occur independently or in association with other genetic conditions such as Down syndrome. Genetic mutations are linked to about half of all isolated cases, with 20% occurring in families. Some cases exhibit autosomal dominant inheritance.

Genetics

Several genes and specific chromosomal regions have been implicated in Hirschsprung's disease, with the RET proto-oncogene accounting for the highest proportion of both familial and sporadic cases. Other notable genes include EDNRB, GDNF, and EDN3.

Pathophysiology

During normal prenatal development, neural crest cells migrate into the large intestine to form the myenteric and submucosal plexuses. In Hirschsprung's disease, this migration is incomplete, resulting in segments of the colon lacking these nerve bodies, leading to a functional obstruction.

Diagnosis

Diagnosis is confirmed through a combination of clinical symptoms and histologic examination. A suction biopsy revealing a lack of ganglionic nerve cells is the gold standard. Radiologic imaging, such as abdominal X-rays and contrast enemas, can assist in diagnosing the condition by showing characteristic signs like a lack of stool in the large intestine or a bulging segment caused by blocked stool.

Treatment

The primary treatment for Hirschsprung's disease is surgical removal of the affected bowel segment followed by reanastomosis. The "pull-through" procedure is the most common surgical technique, where the functioning bowel is connected to the anus.

Colostomy and Other Procedures

Initial treatment may involve a reversible colostomy, where the healthy end of the intestine is attached to an abdominal opening to allow bowel contents to be discharged into a bag. Later, the functional bowel is reconnected to the anus.

The pull-through procedure has evolved into several variations, including the Swenson, Soave, Duhamel, and Boley procedures. Each has unique approaches to removing the affected bowel and reconnecting the healthy sections.

In cases where full bowel control is not achieved, additional treatments like laxatives, high-fibre diets, or procedures such as the Malone antegrade colonic enema (ACE) can be considered.

Epidemiology

Hirschsprung's disease affects approximately 1 in 5,000 newborns and is more common in males than females. It also has a higher incidence in individuals with Down syndrome. Diagnosis typically occurs before the age of 10.

History

The condition was first described in 1691 by Dutch anatomist Frederik Ruysch. Danish physician Harald Hirschsprung provided a detailed description in 1888, giving the disease its name. The first significant genetic discovery related to Hirschsprung's disease was made in 1992, identifying the RET proto-oncogene as a major genetic factor.

Hirschsprung's disease remains a very important area of study due to its significant impact on affected individuals and its association with various genetic syndromes. Understanding its pathophysiology, genetics, and treatment options is essential for effective management.

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Self-assessment MCQs (single best answer)

What is the primary characteristic of Hirschsprung's disease?

Which gene is most commonly associated with Hirschsprung's disease?

What is the gold standard for diagnosing Hirschsprung's disease?

Which of the following is NOT a common symptom of Hirschsprung's disease in newborns?

Hirschsprung's disease is more common in individuals with which genetic condition?

What surgical procedure is commonly used to treat Hirschsprung's disease?

Which of the following syndromes is associated with Hirschsprung's disease?

In Hirschsprung's disease, what developmental process is disrupted, leading to the condition?

Which of the following radiologic imaging techniques can assist in diagnosing Hirschsprung's disease?

What is the estimated incidence of Hirschsprung's disease in newborns?