American Pediatric Surgical Association :: Resources : Hirschsprung's Disease

(This article is in 3 parts. Continue to more information at the bottom of this page.)

HISTORICAL BACKGROUND
Descriptions of children with Hirschsprung's Disease date back to the 17th century, when Ruysch (1691), a Dutch anatomist, described a 5-year-old girl who died of intestinal obstruction. The first clinical description of Hirschsprung's Disease was presented at the Berlin Society of Pediatrics in 1886 by Hirschsprung. He thought that the disease was caused by distention of the colon, as evidenced by the title of his presentation: "Constipation in Newborns Due to Dilation and Hypertrophy of the Colon." As a result of Hirschsprung's presentation, however, attention was focused on the consequences of the abnormality rather than the actual cause of the disease.

An understanding of the cause of Hirschsprung's disease took several more decades. An appreciation that the end of the colon toward the rectum was in most cases the actual problem, was advanced by Tittel (1901). He identified an absence of ganglion cells as the cause of Hirschsprung's disease. Because some children with constipation were included in the diagnosis of Hirschsprung's disease, confusion about the cause continued until the late 1940s.

Ehrenpreis in 1946 was the first to appreciate that the colon became enlarged and distended because of the obstruction caused by the lack of ganglion cells. Swenson and Bill in 1948 were the first to advocate rectal biopsy to make the diagnosis of Hirschsprung's disease and to recommend a treatment plan. This plan involved removal of the aganglionic bowel (bowel lacking ganglion cells) and its replacement with normal intestine that has ganglion cells. Since then, many refinements have been introduced in the evaluation of the constipated child and the newborn with intestinal obstruction that have improved the outcome.

Over the past 50 years, as physicians have become more aware of the disease, the diagnosis of Hirschsprung's disease has been increasingly identified shortly after birth. This is important because Hirschsprung's disease can place a child at increased risk for the development of enterocolitis, infection, and perforation (rupture) of the intestine.

Earlier diagnosis may help prevent these complications. Mortality in the newborn period associated with this disease has declined from 70% in 1954 to as little as 6% in 1992 and 1% in 2000. Additional improvements in the care of surgical patients have contributed to these excellent results.

WHAT IS HIRSCHSPRUNG'S DISEASE AND WHY DOES IT OCCUR?
Normal intestinal motility (the ability for the intestine to move food along the intestinal tract and allow digestion) depends on a coordinated contraction wave that pushes the nutrients down stream from mouth to anus. Patients with Hirschsprung's disease lack normal motility in the segment of bowel that has the Hirschsprung's. This results in a clinical picture that resembles either bowel obstruction, particularly in a newborn baby, or chronic constipation in older children.

The incidence of Hirschsprung's disease is between 1 in 4400 to 1 in 7000 live births. It is the result of failed development of ganglion cells in a portion of the intestine. The ganglion cells are always lacking toward the end of the bowel, most commonly in the rectum and colon. It is extremely rare to have areas of the intestine involved with Hirschsprung's disease interspersed with areas of normal bowel. The precise reason ganglion cells are missing is unknown.

Hirschsprung's disease may affect more than one family member though it is unusual (< 8% of cases). Studies also indicate that as more of the colon is involved and lacks ganglion cells the inherited incidence increases. About 15% of patients with Hirschsprung's disease have trisomy 21 (Down's Syndrome). The precise relationship of this genetic abnormality to the development of Hirschsprung's disease has yet to be defined.

The first association of a specific genetic abnormality in Hirschsprung's disease was reported in 1992. Studies allowed investigators to narrow the search for a "Hirschsprung's gene" to a region that overlapped what is called the RET proto-oncogene. The RET proto-oncogene seems to play a major role in the development of the "myenteric nervous system" of which ganglion cells are a part. There may also be other factors that prohibit ganglion cells from developing or migrating into bowel where they are supposed to be. Further study is needed to determine the exact cause for all of the factors that might cause Hirschsprung's disease.

PATHOLOGIC ANATOMY
Hirschsprung's disease or lack of ganglion cells is confined to the sigmoid colon or rectum in 75% to 80% of infants with this problem (Figure 1).

Figure 1. A barium enema showing a transition zone (black arrow). This is the area between the big, distended area which has ganglion cells (white arrow) and the part with Hirschsprung’s disease which is in small and in spasm (White arrowhead). This barium enema demonstrates the typical transition zone in the sigmoid-rectal area of the large intestine.

The transition between normal and abnormal bowel may be found anywhere between the esophagus and anus and occurs in the small bowel in only 5% of affected infants. The remaining 15% of patients have progressively longer lengths of large intestine that are missing ganglion cells (Figure 2). Classically the bowel just before the segment with Hirschsprung's disease becomes distended and enlarged. This distended bowel has ganglion cells. The characteristic problem in the bowel with Hirschsprung's is the absence of ganglion cells.

Figure 2: A barium enema showing a “long segment” Hirschsprung’s disease. The transition zone is in the large intestine in an area going across the abdomen called the transverse colon. The arrow demonstrates the area of the transition zone between the enlarged area which has ganglion cells (normal) and the small area which does not (Hirschsprung’s disease).

Figure 3: Sigmoid colon showing a transition zone. The big, enlarged colon is normal while the smaller colon has the Hirschsprung’s disease. The arrow points to the transition zone.

Figure 4: A huge “megacolon” consisting of sigmoid colon in an older child with Hirschsprung’s disease. There is a transition zone in the last part of the sigmoid colon (arrow) which has a “funnel.” A colostomy was formed to allow the colon to get smaller before a pullthrough was performed.

Between the normal bowel with ganglion cells and the abnormal bowel without ganglion cells is what is called a transition zone. (Figure 3) There are some but not many ganglion cells here. Externally the transition looks like a short funnel or tapered segment of the colon (Figure 4). In order to be sure what is normal, small pieces of tissue (biopsies) must be examined under the microscope to confirm the diagnosis and to help make clinical decisions. The transition zone is often obvious on x-rays by the time a baby is a few weeks old as the obstructed Hirschsprung's segment leads to progressive and what is called "congenital megacolon." (ie, a very large, segment of intestine. (See Figures 5 and 6).

Figure 5: (left) The X-ray of the abdomen shows enlarged intestine (arrow). (right) The arrow demonstrates the transition zone on contrast enema.

Figure 6: Dilated bowel above area of transition zone in a 3 year old with Hirschsprung’s disease. This area is normal and does not have Hirschsprung’s Disease. However, the large intestine is huge and doing a pullthrough would be difficult. A colostomy would be formed before trying to pull the intestine down to the anus.

The transition zone in newborn infants may be subtle or undetectable by x-rays because the bowel has not had time to become enlarged or distended. The identification of the transition zone may be a problem for the surgeon or radiologist with these particular patients. A barium enema study can be used to help identify a transition zone and to suggest the diagnosis of Hirschsprung's disease but a normal barium enema can never completely rule out the diagnosis of Hirschsprung's disease. A biopsy of the bowel is required to definitely establish the diagnosis (Figures 7, 8 and 9). If ganglion cells are present on the biopsy specimen, the diagnosis of Hirschsprung's disease can be excluded except in rare instances. (Ultra short segment Hirschsprung's disease, see below).

Figure 7: A diagram of the layers of the rectum. The rectal biopsy is taken from the “submucosa” or the “intermuscular area” between the circular and longitudinal layers of muscle where the ganglion cells should be located in the normal rectum.

Figure 8: A rectal biopsy demonstrating ganglion cells (arrows). There is no Hirschsprung’s disease.

Figure 9: A rectal biopsy showing a lack of ganglion cells in the “submucosa” and large nerves (arrow). This biopsy is consistent with Hirschsprung’s disease.