HIRSCHSPRUNG DISEASE

Jacob C. Langer

Hirschsprung disease is a developmental disorder of the intrinsic component of the enteric

nervous system that is characterized by the absence of ganglion cells in the myenteric and
submucosal plexuses of the distalintestine. Because these cells are responsible for normal
peristalsis, patients with Hirschsprung disease present with functional intestinal obstruction
at the level of aganglionosis. In most cases the aganglionosis involves the rectum or
rectosigmoid, but it can extend for varying lengths, and in 5% to 10% of cases can involve
the entire colon or even a significant amount of the small intestine. The incidence of
Hirschsprung disease is approximately 1 in 5000 live-born infants.

History
The condition of “congenital megacolon” has been recognized for centuries. The first
description of this condition was in the seventeenth century by Frederick Ruysch, who
described a 5-year-old child dying from an intestinal obstruction, followed by another
account of a child with congenital megacolon by Battini in 1800.1 It was not until 1887 that
Harald Hirschsprung, a pathologist at Queen Louise Children’s Hospital in Copenhagen,
described two cases of the condition that
ultimately bore his name.2 Until the beginning of the twentieth century, most children with
congenital megacolon died, presumably from malnutrition and enterocolitis. Because the
underlying pathologic abnormality was not recognized, surgeons who operated on these
children usually resected the dilated proximal bowel with or without primary anastomosis,
with mixed results.3 The absence of ganglion cells in the distal colon of a child with
Hirschsprung disease was first noted by Tittel in 1901. Over the following decades numerous
papers were published to document abnormalities of innervation within the colon and
recognize the absence of ganglion cells that is now pathognomonic of Hirschsprung disease.
The first surgical recognition of aganglionosis as the cause of congenital megacolon was by
Ehrenpreis in 1946. In a landmark paper, Whitehouse and Kernohan summarized the
literature and presented a series of cases of their own, which documented that the
aganglionosis within the distal colon or rectum was the cause of the functional obstruction.4
In 1949 Swenson published a paper in the New England Journal of Medicine recommending
rectosigmoidectomy with preservation of the sphincters as the optimal treatment of this
disease.5 This operation was originally performed without a decompressing colostomy.6
However, technical difficulties in small infants and the debilitated and malnourished state in
which mostchildrenpresentedcaused mostsurgeonstoadopt a multistaged approach with
colostomy as the initial step,6 an approach that became the standard of care for decades. In
recent years, improvements in surgical technique and earlier suspicion and diagnosis of the
disease have resulted in an evolution toward one-stage and minimal access procedures.
These advances have resulted in significantly improved morbidity and mortality in infants
with Hirschsprung disease.

Etiology and Genetics

Ganglion cells are derived from the neural crest. By 13 weeks postconception, the neural
crest cells have undergone a process of migration through the gastrointestinal tract from
proximal to distal, after which they differentiate into mature ganglion cells.7 In infants with
Hirschsprung disease this process is disturbed, so the ganglion cells are absent in the distal
bowel. There are two theories as to why this occurs. The most prevalent is that the neural
crest cells never reach the distal intestine because they either mature or differentiate into
ganglion cells earlier than they should. Data supporting this theory come from
spontaneously occurring animal models of aganglionosis8 and fromstudiesofnormalneural
crest cellmigration done in chick embryos and human fetuses.9,10 The second theory is that
the ganglion cells do reach their destination but fail to survive or proliferate. Data in support
of this theory include animal studies suggesting that there are at least two sourcesof neural
crest cells (vagal and sacral), with migration both proximally and distally. In addition, a
number of studies have suggested that the smooth muscle and extracellular matrix in the
aganglionic bowel provides an inhospitable microenvironment for neuronal growth.11,12 It
is likely that Hirschsprung disease is actually a heterogeneous condition with multiple
genetic causes and etiologic mechanisms, so each of these theories may be true in individual
cases.