Definition
Hirschsprung's disease, also known as congenital megacolon or
aganglionic megacolon, is an abnormality in which certain nerve
fibers are absent in segments of the bowel, resulting in severe
bowel obstruction.Description
Hirschsprung's disease is caused when certain nerve cells
(called parasympathetic ganglion cells) in the wall of the
large intestine (colon) do not develop before birth. Without these
nerves, the affected segment of the colon lacks the ability to relax
and move bowel contents along. This causes a constriction and as a
result, the bowel above the constricted area dilates due to stool
becoming trapped, producing megacolon (dilation of the colon). The
disease can affect varying lengths of bowel segment, most often
involving the region around the rectum. In up to 10% of children,
however, the entire colon and part of the small intestine are
involved.
Hirschprung's disease occurs once in every 5,000 live births, and
it is about four times more common in males than females. Between 4%
and 50% of siblings are also afflicted. The wide range for
recurrence is due to the fact that the recurrence risk depends on
the gender of the affected individual in the family (i.e., if a
female is affected, the recurrence risk is higher) and the length of
the aganglionic segment of the colon (i.e., the longer the segment
that is affected, the higher the recurrence risk).
Radiographic Appearance
Conventional abdominal x-ray usually demonstrates low
obstruction with multiple air fluid levels and bowel distention. The
differential diagnosis usually includes imperforate anus, colonic
atresia, , meconium plug and meconium ileus.
Barium enema is usually useful in diagnosing Hirschsprung's
disease, and is performed to evaluate for a transition zone. In
Hirschsprung's disease the enema demonstrates an essentially normal
caliber rectum and at some point in the upper rectum or distal
sigmoid, there is an abrupt transition to an area of grossly dilated
bowel. The rectosigmoid index is used to evaluate for a transition
zone. A rectum to sigmoid ratio of greater than .9 exclude the
diagnosis of Hirschsprung's disease.
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Causes and symptoms
Hirschsprung's disease occurs early in fetal development when,
for unknown reasons, there is either failure of nerve cell
development, failure of nerve cell migration, or arrest in nerve
cell development in a segment of bowel. The absence of these nerve
fibers, which help control the movement of bowel contents, is what
results in intestinal obstruction accompanied by other symptoms.
There is a genetic basis to Hirschsprung's disease, and it is
believed that it may be caused by different genetic factors in
different subsets of families. Proof that genetic factors contribute
to Hirschprung's disease is that it is known to run in families, and
it has been seen in association with some chromosome abnormalities.
For example, about 10% of children with the disease have Down
syndrome (the most common chromosome abnormality). Molecular
diagnostic techniques have identified many genes that cause
susceptibility to Hirschprung's disease. As of 200l, there are a
total of six genes: the RET gene, the glial cell line-derived
neurotrophic factor gene, the endothelin-B receptor gene, endothelin
converting enzyme, the endothelin-3 gene, and the Sry-related
transcription factor SOX10. Mutations that inactivate the RET gene
are the most frequent, occurring in 50% of familial cases (cases
which run in families) and 15-20% of sporadic (non-familial) cases.
Mutations in these genes do not cause the disease, but they make the
chance of developing it more likely. Mutations in other genes or
environmental factors are required to develop the disease, and these
other factors are not understood.
For persons with a ganglion growth beyond the sigmoid segment of
the colon, the inheritance pattern is autosomal dominant with
reduced penetrance (risk closer to 50%). For persons with smaller
segments involved, the inheritance pattern is multifactorial (caused
by an interaction of more than one gene and environmental factors,
risk lower than 50%) or autosomal recessive (one disease gene
inherited from each parent, risk closer to 25%) with low penetrance.
The initial symptom is usually severe, continuous constipation.
A newborn may fail to pass meconium (the first stool) within 24
hours of birth, may repeatedly vomit yellow or green colored bile
and may have a distended (swollen, uncomfortable) abdomen.
Occasionally, infants may have only mild or intermittent
constipation, often with diarrhea.
While two-thirds of cases are diagnosed in the first three months
of life, Hirschsprung's disease may also be diagnosed later in
infancy or childhood. Occasionally, even adults are diagnosed with a
variation of the disease. In older infants, symptoms and signs may
include anorexia (lack of appetite or inability to eat), lack of the
urge to move the bowels or empty the rectum on physical
examination, distended abdomen, and a mass in the colon that can
be felt by the physician during examination. It should be suspected
in older children with abnormal bowel habits, especially a history
of constipation dating back to infancy and ribbon-like stools.
Occasionally, the presenting symptom may be a severe intestinal
infection called enterocolitis, which is life threatening. The
symptoms are usually explosive, watery stools and fever in a
very ill-appearing infant. It is important to diagnose the condition
before the intestinal obstruction causes an overgrowth of bacteria
that evolves into a medical emergency. Enterocolitis can lead to
severe diarrhea and massive fluid loss, which can cause death
from dehydration unless surgery is done immediately to
relieve the obstruction.
Diagnosis
Hirschsprung's disease in the newborn must be distinguished from
other causes of intestinal obstruction. The diagnosis is suspected
by the child's medical history and physical examination, especially
the rectal exam. The diagnosis is confirmed by a barium enema
x ray, which shows a picture of the bowel. The x ray will indicate
if a segment of bowel is constricted, causing dilation and
obstruction. A biopsy of rectal tissue will reveal the absence of
the nerve fibers. Adults may also undergo manometry, a balloon study
(device used to enlarge the anus for the procedure) of internal anal
sphincter pressure and relaxation.
Treatment
Hirschsprung's disease is treated surgically. The goal is to
remove the diseased, nonfunctioning segment of the bowel and restore
bowel function. This is often done in two stages. The first stage
relieves the intestinal obstruction by performing a colostomy.
This is the creation of an opening in the abdomen (stoma) through
which bowel contents can be discharged into a waste bag. When the
child's weight, age, or condition is deemed appropriate, surgeons
close the stoma, remove the diseased portion of bowel, and perform a
"pull-through" procedure, which repairs the colon by connecting
functional bowel to the anus. This usually establishes fairly normal
bowel function.
Prognosis
Overall, prognosis is very good. Most infants with
Hirschsprung's disease achieve good bowel control after surgery, but
a small percentage of children may have lingering problems with
soilage or constipation. These infants are also at higher risk for
an overgrowth of bacteria in the intestines, including subsequent
episodes of enterocolitis, and should be closely followed by a
physician. Mortality from enterocolitis or surgical complications in
infancy is 20%.
Prevention
Hirschsprung's disease is a congenital abnormality that has no
known means of prevention. It is important to diagnose the condition
early in order to prevent the development of enterocolitis.
Genetic counseling can be offered to a couple with a previous
child with the disease or to an affected individual considering
pregnancy to discuss recurrence risks and treatment options.
Prenatal diagnosis is not available.
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