Hirschsprung disease is a developmental disorder of the enteric nervous system and is characterized by an absence of ganglion cells in the distal

colon resulting in a functional obstruction.[1]

Hirschsprung disease. Contrast enema demonstrating transition zone in the rectosigmoid region. Although this condition was described by Ruysch in 1691 and popularized by Hirschsprung in 1886, the pathophysiology was not clearly determined until the middle of the 20th century, when Whitehouse and Kernohan described the aganglionosis of the distal intestine as the cause of obstruction in their series of patients.[2] In 1949, Swenson described the first consistent definitive procedure for Hirschsprung disease, rectosigmoidectomy with coloanal anastomosis. Since then, other operations have been described, including the Duhamel and Soave techniques. More recently, advances in surgical technique, including minimally invasive procedures, and earlier diagnosis have resulted in decreased morbidity and mortality for patients with Hirschsprung disease. Most cases of Hirschsprung disease are now diagnosed in the newborn period. Hirschsprung disease should be considered in any newborn who fails to pass meconium within 24-48 hours after birth. Although contrast enema is useful in establishing the diagnosis, full-thickness rectal biopsy remains the criterion standard. Once the diagnosis is confirmed, the basic treatment is to remove the poorly functioning aganglionic bowel and to create an anastomosis to the distal rectum with the healthy innervated bowel (with or without an initial diversion).

Pathophysiology
Congenital aganglionosis of the distal bowel defines Hirschsprung disease. Aganglionosis begins with the anus, which is always involved, and continues proximally for a variable distance. Both the myenteric (Auerbach) plexus and the submucosal (Meissner) plexus are absent, resulting in reduced bowel peristalsis and function. The precise mechanism underlying the development of Hirschsprung disease is unknown. Enteric ganglion cells are derived from the neural crest. During normal development, neuroblasts will be found in the small intestine by the 7th week of gestation and will reach the colon by the 12th week of gestation.[3] One possible etiology for Hirschsprung disease is a defect in the

migration of these neuroblasts down their path to the distal intestine. Alternatively, normal migration may occur with a failure of neuroblasts to survive, proliferate, or differentiate in the distal aganglionic segment. Abnormal distribution in affected intestine of components required for neuronal growth and development, such as fibronectin, laminin, neural cell adhesion molecule (NCAM), and neurotrophic factors, may be responsible for this theory.[4, 5, 6] Additionally, the observation that the smooth muscle cells of aganglionic colon are electrically inactive when undergoing electrophysiologic studies also points to a myogenic component in the development of Hirschsprung disease.[7] Finally, abnormalities in the interstitial cells of Cajal, pacemaker cells connecting enteric nerves and intestinal smooth muscle, have also been postulated as an important contributing factor.[8, 9] Three neuronal plexus innervate the intestine: the submucosal (ie, Meissner) plexus, the intermuscular (ie, Auerbach) plexus, and the smaller mucosal plexus. All of these plexus are finely integrated and involved in all aspects of bowel function, including absorption, secretion, motility, and blood flow. Normal motility is primarily under the control of intrinsic neurons. Bowel function is adequate, despite a loss of extrinsic innervation. These ganglia control both contraction and relaxation of smooth muscle, with relaxation predominating. Extrinsic control is mainly through the cholinergic and adrenergic fibers. The cholinergic fibers cause contraction, and the adrenergic fibers mainly cause inhibition. In patients with Hirschsprung disease, ganglion cells are absent, leading to a marked increase in extrinsic intestinal innervation. The innervation of both the cholinergic system and the adrenergic system is 2-3 times that of normal innervation. The adrenergic (excitatory) system is thought to predominate over the cholinergic (inhibitory) system, leading to an increase in smooth muscle tone. With the loss of the intrinsic enteric inhibitory nerves, the increased tone is unopposed and leads to an imbalance of smooth muscle contractility, uncoordinated peristalsis, and a functional obstruction.

Approximately 10% of patients have a positive family history. This is more common in patients with longer segment disease. Hirschsprung disease should be considered in any newborn with delayed passage of meconium or in any child with a history of chronic constipation since birth. Other symptoms include bowel obstruction with bilious vomiting, abdominal distention, poor feeding, and failure to thrive. Prenatal ultrasound demonstrating bowel obstruction is rare, except in cases of total colonic involvement.[18] Older children with Hirschsprung disease have usually had chronic constipation since birth. They may also show evidence of poor weight gain. Older presentation is more common in breastfed infants who will typically develop constipation around the time of weaning. Despite significant constipation and abdominal distension, children with Hirschsprung disease rarely develop encopresis. In contrast, children with functional constipation or stool-withholding behaviors more commonly develop encopresis.

About 10% of children may present with diarrhea caused by enterocolitis, which is thought to be related to stasis and bacterial overgrowth. This may progress to colonic perforation, causing life-threatening sepsis.[19] In a study of 259 consecutive patients, Menezes et al reported that 57% of patients presented with intestinal obstruction, 30% with constipation, 11% with enterocolitis, and 2% with intestinal perforation.[20]

Hirschsprung's disease (HSCR), or congenital aganglionic megacolon is a serious medical problem where the enteric nervous system is missing from the end of the bowel. The enteric nervous system is a complex network of neurons (i.e., ganglion cells) and glia that controls most aspects of intestinal function. When the ENS is absent, the region of the bowel that is aganglionic fails to relax causing a blockage in the bowel[1]. People with Hirschsprung disease always have aganglionosis (lack of neurons) at the end of the bowel, but the length of bowel that is aganglionic varies. Severe symptoms may occur with even short segments of aganglionosis and symptom severity does not correlate well with the extent of aganglionic bowel.

Hirschsprungs disease
Congenital megacolon

Last reviewed: November 2, 2009. Hirschsprung's disease is a blockage of the large intestine due to improper muscle movement in the bowel. It is a congenital condition, which means it is present from birth.

Causes, incidence, and risk factors

Muscle contractions in the gut help digested materials move through the intestine. This is called peristalsis. Nerves in between the muscle layers trigger the contractions. In Hirschsprung's disease, the nerves are missing from a part of the bowel. Areas without such nerves cannot push material through. This causes a blockage. Intestinal contents build up behind the blockage, causing the bowel and abdomen to become swollen. Hirschsprung's disease causes about 25% of all newborn intestinal blockages. It occurs five times more often in males than in females. Hirschsprung's disease is sometimes associated with other inherited or congenital conditions, such as Down syndrome.

Symptoms
Symptoms that may be present in newborns and infants include:

Difficulty with bowel movements Failure to pass meconium shortly after birth Failure to pass a first stool within 24 - 48 hours after birth Infrequent but explosive stools Jaundice Poor feeding Poor weight gain Vomiting Watery diarrhea (in the newborn)

Symptoms in older children:

Constipation that gradually gets worse Fecal impaction Malnutrition Slow growth Swollen belly

Signs and tests

Milder cases may not be diagnosed until a later age. During a physical examination, the doctor may be able to feel loops of bowel in the swollen belly. A rectal examination may reveal a loss of muscle tone in the rectal muscles. Tests used to help diagnose Hirschsprung's disease may include:

Abdominal x-ray Anal manometry (a balloon is inflated in the rectum to measure pressure in the area) Barium enema Rectal biopsy

Treatment
Before surgery, a procedure called serial rectal irrigation helps relieve pressure in (decompress) the bowel. The abnormal section of colon must be removed with surgery. Most commonly, the rectum and abnormal part of the colon are removed. The healthy part of the colon is then pulled down and attached to the anus. Sometimes this can be done in one operation. However, it is often done in two parts. A colostomy is performed first, and another procedure is performed later in the child's first year of life.

Expectations (prognosis)
Symptoms improve or go away in most children after surgery. A small number of children may have constipation or problems controlling stools (fecal incontinence). Children who get treated early or who have a shorter segment of bowel involved have a better outcome.

Complications

Inflammation and infection of the intestines (enterocolitis) may occur before surgery, and sometimes during the first 1-2 years afterwards. Symptoms are severe, including swelling of the abdomen, foul-smelling watery diarrhea, lethargy, and poor feeding. Perforation or rupture of the intestine Short bowel syndrome, a condition that can lead to malnourishment and dehydration