Hirschprung Disease

Description

Hirschsprung’s disease (HD) is a congenital disorder characterised by the absence of ganglion cells in the distal colon, resulting in chronic constipation and intestinal obstruction. This is due to a failure of neural crest cell migration during embryonic development, leading to a lack of myenteric (Auerbach’s) and submucosal (Meissner’s) plexuses in the affected region of the intestine. The segment without these nerve cells, known as the aganglionic segment, cannot relax and pass stool effectively, leading to the characteristic symptoms of the disease.

Pathogenesis

The pathogenesis of Hirschsprung’s disease is fundamentally linked to the failed craniocaudal migration, proliferation, differentiation, or survival of neuroblasts originating from the neural crest, along the bowel wall during embryogenesis. This failure results in an absence of parasympathetic intrinsic ganglion cells in the myenteric and submucosal plexuses of the enteric nervous system, affecting the peristalsis of the gut and resulting in relaxation failure of the aganglionic segment. It usually affects the rectosigmoid junction and involves a short-segment in the majority of cases. The RET proto-oncogene is the most commonly mutated gene associated with Hirschsprung’s disease, but other genes such as GDNF, EDNRB, and SOX10 also play a role.

Subtypes

Hirschsprung’s disease can be classified anatomically according to the length of the aganglionic segment.

• Ultra-short segment disease (USSHD): This is a rare type where the aganglionic segment involves only the internal anal sphincter or a short segment within the rectum. Diagnosis can be challenging as routine biopsies may miss the affected segment.
• Short-segment disease (SSHD): The most common type, accounting for about 80% of cases. In short-segment disease, the aganglionic segment involves the rectosigmoid area. The proximal boundary of the affected segment is within the sigmoid colon.
• Long-segment disease (LSHD): This occurs in approximately 15-20% of cases. In long-segment disease, the aganglionic segment extends proximally beyond the sigmoid colon and may involve the entire colon.
• Total colonic aganglionosis (TCA): This is a more severe and rare form of Hirschsprung’s disease, occurring in about 2-13% of cases. The entire colon and sometimes part of the small intestine lack ganglion cells.
• Total intestinal aganglionosis (TIA): This is an extremely rare and severe variant where the aganglionic segment involves the entire bowel. This condition is often incompatible with life due to the extensive involvement of the intestine.

Epidemiology, Risk Factors, and Associations

• Hirschsprung’s disease affects approximately 1 in 5000 live births.
• It typically affects full-term infants during the first weeks of life. It is extremely rare in premature infants.
• There is a male predominance, with a male-to-female ratio of approximately 4:1 in the classic form of the disease.
• The disease has a familial tendency, and the risk of recurrence in siblings is about 4%.
• Hirschsprung’s disease can be associated with other genetic conditions such as Down syndrome (occurring in up to 10% of individuals with Hirschsprung’s disease) and other congenital anomalies.

Clinical Features

The symptoms of Hirschsprung’s disease can present at any age but most commonly in the neonatal period.

• In newborns, a common sign is failure to pass meconium within the first 48 hours of life.
• Other symptoms may include constipation, abdominal distension, vomiting, and poor feeding.
• In older children, symptoms may include chronic constipation, failure to thrive, and episodes of enterocolitis.

Complications

• Intestinal obstruction in neonates
• Perforation
• Enterocolitis

Pathological Features

• Histopathological examination, usually through rectal suction biopsy, is the definitive test for Hirschsprung’s disease. The absence of ganglion cells in the submucosal (Meissner’s) and myenteric (Auerbach’s) plexus is the key finding.
• There is hypertrophy of the nerve trunks in the muscular layers and an increased number of acetylcholinesterase-positive nerve fibers in the mucosa.
• Inflammatory changes such as enterocolitis may also be seen.

Radiological Features

General

• Findings are primarily bowel obstruction.
• Most commonly affected bowel segment is the rectosigmoid junction.
• The transition zone represents the zone between normal and stenotic aganglionic colonic segment. It is typically funnel- or inverted cone- shaped.
• Anorectal manometry can be used to evaluate the rectoanal inhibitory reflex (RAIR), which is typically absent in Hirschsprung’s disease.

XR

• Distal colonic dilatation with proximal faecal loading, inspissated meconium and a transition zone near the rectosigmoid colon
• Pneumoperitoneum suggests perforation

FL

• Contrast enema may demonstrate the transition zone
  • Rectosigmoid ratio < 1 compatible with HD (normally >1 as the rectum is larger in diameter than the sigmoid)
  • Water-soluble contrast preferred for therapeutic benefit
  • Non-balloon tip catheter to be used on neonates
• The affected aganglionic segment demonstrates small calibre and fasciculation/saw-tooth irregularity
• Dilatation of large and small bowel proximal to transition zone with marked retention of contrast on delayed radiographs after 24 hours.
• Enemate may be normal in 30% of cases

Staging

There’s no conventional staging system for Hirschsprung’s disease, as it’s a congenital disorder. Rather, it’s classified based on the length of the aganglionic segment, which can vary from only the rectosigmoid region (short-segment disease) to the entire colon or even more extended segments of the bowel (long-segment disease). It’s also classified by the onset of symptoms into neonatal, infancy, and childhood-onset forms.

Diagnosis

• Diagnosis is by rectal biopsy

Differential Diagnosis

• Functional constipation: This is the most common condition to differentiate from Hirschsprung’s disease. However, the persistence of constipation despite appropriate medical treatment should raise suspicion for Hirschsprung’s disease.
• Meconium plug syndrome: This condition can also present with failure to pass meconium and intestinal obstruction in the neonatal period. Resolves after contrast enema.
• Intestinal atresia or stenosis: These can also present with symptoms of intestinal obstruction.
• Neurogenic bowel dysfunction: Other causes of neurogenic bowel dysfunction can mimic Hirschsprung’s disease, such as spinal cord anomalies.

Management

The primary treatment for Hirschsprung’s disease is surgery to bypass or remove the aganglionic segment of the bowel. This can be done through a pull-through procedure, where the normal bowel is pulled through and sewn to the anus, or an ostomy, where the bowel is rerouted to an opening in the abdomen.