Victor J. Bishop Reprinted in A Circle of Friends II. Bringing Love and Hope to Those with Down Syndrome. Mullaly, G. & Saxton-Bolt, D. (Compilers)

Reprinted with the permission of the author and the compilers

Introduction

Hirschsprung disease, also known as congenital intestinal aganglionosis or aganglionic megacolon, is a congenital disorder characterized by absence of enteric ganglia along a variable length of the intestine, named after Harald Hirschsprung (1830-1916), a Danish physician who first described the disease in 1888. The Hirschsprung Danish Art Collection in Copenhagen is named after this family. The first recorded observation of Hirschsprung disease is credited to Frederick Ruysch, who published an autopsy report in 1691. It was not until 1948 that its pathogenesis was recognized. Whitehouse and Kernohan documented the absence of ganglion cells and their findings led to the development of an effective surgical treatment by Swenson and Bill.

Hirschsprung disease occurs in about one out of every 5,000 live births Passarge (1967). The ratio of males to females may be as high as 4:1. From the fifth to the twelfth week of pregnancy, nerve cells (ganglion) form in a downward manner in the alimentary tract. For some unknown genetic reason, the nerve cell migration is not completed in the baby with Hirschsprung disease.

Hirschsprung disease is a lack of ganglion cells in the wall of the bowel. The ganglia control the squeezing action called peristalsis which is the coordinated relaxation of the bowel wall that is necessary for the stool to advance through the intestines. The portion of bowel without ganglia cannot relax. The large intestine remains collapsed, caused by inadequate motility (muscular movement of the bowel) and stools cannot pass. Bowel contents build up behind the obstruction, which always ends at the anus.

Diagnosis may be considered when a newborn fails to pass stool (meconium) within 24 hours of birth, develops vomiting which may be stained, or shows signs of abdominal distention. Older children may present with severe constipation. A small number of children may also develop inflammation in the colon (enterocolitis) which will cause fever, diarrhea, and abdominal distention. Diagnosis may be confirmed with barium enema and rectal biopsy.

Down Syndrome Incidence

Hirschsprung disease was first described in a constipated infant with Down syndrome in Cuba Vacher et al. (1956). Hirschsprung disease is a frequent finding in cases of Down syndrome. Six of 63 probands in the Passarge (1967) study were also cases of Down syndrome. Garver et al. (1985) found a significant association between Hirschsprung disease and Down syndrome in that 5.9% of the 134 cases had both, where 103 had the short-segment and 31 had the long-segment type of aganglionosis. For the 2 types, the sex ratio was 5.4 and 1.4, respectively. The following table shows the length of aganglionosis for Down syndrome, taken from Croaker et al. (1998):

Quinn et al. (1994) reported seventeen (13%) of 135 patients presenting with Hirschsprung disease, between 1975 and 1992, had Down syndrome. Goldberg et al. (1984) identified 33 cases of Hirschsprung disease between 1969 and 1977 where 9% had Down syndrome, while Sabiston et al. mention that 3%-5% of infants with Hirschsprung disease have Down syndrome.

Puffenberger et al. (1994) found preliminary evidence for a genetic modifier of HSCR on 21q22 in the large Mennonite founder kindred with Hirschsprung disease in which they demonstrated the location of a recessive gene for the disorder on 13q22 using identity-by-descent and linkage disequilibrium analysis.

It is believed that there is at least one gene on chromosome 21 which can cause Hirschsprung disease when present in two defective copies. It is not known whether this gene has some other version (allele) which explains Hirschsprung disease in Down syndrome since there may be as many as three different genes involved. Hirschsprung disease can also be caused by genes on other chromosomes and inherited in different ways: dominant — a change in one gene is enough to cause disease; recessive — both genes of a pair need to have a change before a child gets disease; multifactorial — many genes intereact with environmental factors to cause disease.

Biospy

The definitive test for Hirschsprung's disease is a rectal biopsy. The specimen is taken from the rectum just above the anus, and the pathologist then looks under the microscope for the presence or absence of nerve cells in the bowel wall. In most children, the technique used is called a "suction rectal biopsy". This is normally done without anesthesia, because there are no pain fibers in the rectum. In some children, particularly those who are older or in whom the suction biopsy has not been successful, a "punch biopsy" or a "full-thickness biopsy" may be necessary. These are usually done under general anesthesia. The risks of rectal biopsy include bleeding, perforation of the rectum, and infection, but these complications are very rare, occuring less than 1% of the time.

Surgery

Treating Hirschsprung disease requires surgery to remove the affected bowel and then join the healthy bowel segments. There are three different approaches, each with a high rate of success. The choice depends on the overall health, age, weight, condition of the child, and the training and experience of the surgeon.

The surgical procedure is designed to remove the aganglionic segment, then bring the healthy bowel down into the rectum, and join it to the rectal wall just above the anus; this procedure is called a pull-through operation. In some cases, a temporary stoma (colostomy or ileostomy) may be recommended prior to the pull-through. Some surgeons routinely perform a stoma only if the child is too small or critically ill. In a colostomy, the colon is brought out to the surface of the abdomen so that stool can be discharged into a special bag for disposal, while an ileostomy is a surgically created opening of the ileum (lower part of the small intestine) to the surface of the abdomen. A bag specially designed for collecting waste is attached to the skin by an adhesive substance. The stoma is pink or red in color. Ointments and gauze placed around the stoma with a diaper covering is an alternative to a bag in an infant.

In children who have a preliminary colostomy or ileostomy, the stoma can be closed at the time of the pull-through, or, in some cases, at a third operation after it is clear that the pull-through is working.

For most children with Hirschsprung disease, there are no long-term complications after successful surgery. A better outcome is associated with early treatment. A significant minority of children, though, are troubled with persistent constipation, encopresis (stool incontinence), or persistent enterocolitis (inflammation in the colon).

Fecal Soiling

In a retrospective review of all children treated for Hirschsprung's disease over the past 22 years at a single pediatric institution, Marty et al. (1995), reported that surgical reconstruction for Hirschsprung disease provides near-normal gastrointestinal function for the majority of children, but long-term follow-up shows significant residual problems with fecal soiling in 12.6% of the patients and severe fecal soiling in 7.1%.

Quinn et al. (1994) reported that only one of the 13 patients with this dual diagnosis had normal bowel function. Eight had persistent soiling, and two had reverted to permanent stomata. These data suggest that long-term bowel function in children with Hirschsprrung disease and Down syndrome is poor and should be taken into consideration when planning the management.

The anal sphincter functions normally in terms of continence. The only abnormality observed is that it does not relax when the rectum is distended (so-called anal sphincter "hypertonicity", which is present in all children with Hirschsprung disease). This results in constipation in some children, which can lead to secondary stool holding and encopresis (leakage of stool with incontinence on that basis). Children with Down syndrome are prone to have more trouble with this problem, than those without Down syndrome.

References

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