ultimately bore his name.

2 Until the beginning of the twenti-

eth 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 anasto-
mosis, 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 patho-
gnomonic of Hirschsprung disease. The first surgical recogni-
tion 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
CHAPTER 101 decompressing colostomy.6 However, technical difficulties in
small infants and the debilitated and malnourished state in
which most children presented caused most surgeons to adopt
a multistaged approach with colostomy as the initial step,6 an
Hirschsprung 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
Disease evolution toward one-stage and minimal access procedures.
These advances have resulted in significantly improved
morbidity and mortality in infants with Hirschsprung disease.
Jacob C. Langer

Etiology and Genetics

Hirschsprung disease is a developmental disorder of the in- ------------------------------------------------------------------------------------------------------------------------------------------------

trinsic component of the enteric nervous system that is char- Ganglion cells are derived from the neural crest. By 13 weeks
acterized by the absence of ganglion cells in the myenteric and postconception, the neural crest cells have undergone a pro-
submucosal plexuses of the distal intestine. Because these cells cess of migration through the gastrointestinal tract from prox-
are responsible for normal peristalsis, patients with Hirsch- imal to distal, after which they differentiate into mature
sprung disease present with functional intestinal obstruction ganglion cells.7 In infants with Hirschsprung disease this pro-
at the level of aganglionosis. In most cases the aganglionosis cess is disturbed, so the ganglion cells are absent in the distal
involves the rectum or rectosigmoid, but it can extend for bowel. There are two theories as to why this occurs. The most
varying lengths, and in 5% to 10% of cases can involve the en- prevalent is that the neural crest cells never reach the distal
tire colon or even a significant amount of the small intestine. intestine because they either mature or differentiate into gan-
The incidence of Hirschsprung disease is approximately 1 in glion cells earlier than they should. Data supporting this the-
5000 live-born infants. ory come from spontaneously occurring animal models of
aganglionosis8 and from studies of normal neural crest cell mi-
gration done in chick embryos and human fetuses.9,10 The
second theory is that the ganglion cells do reach their destina-
History tion but fail to survive or proliferate. Data in support of this
------------------------------------------------------------------------------------------------------------------------------------------------
theory include animal studies suggesting that there are at least
The condition of “congenital megacolon” has been recognized two sources of neural crest cells (vagal and sacral), with migra-
for centuries. The first description of this condition was in the tion both proximally and distally. In addition, a number of
seventeenth century by Frederick Ruysch, who described a studies have suggested that the smooth muscle and extracel-
5-year-old child dying from an intestinal obstruction, followed lular matrix in the aganglionic bowel provides an inhospitable
by another account of a child with congenital megacolon by microenvironment for neuronal growth.11,12 It is likely that
Battini in 1800.1 It was not until 1887 that Harald Hirsch- Hirschsprung disease is actually a heterogeneous condition
sprung, a pathologist at Queen Louise Children’s Hospital with multiple genetic causes and etiologic mechanisms, so
in Copenhagen, described two cases of the condition that each of these theories may be true in individual cases.
1265
1266 PART VII ABDOMEN

The heterogeneous nature of Hirschsprung disease is sup- Hirschsprung disease from more common causes of constipa-
ported by increasing evidence that mutations in a variety of tion. Clinical features that point to this diagnosis include
genes may be responsible.13–15 The most commonly identified failure to pass meconium in the first 48 hours of life, failure
gene is the RET proto-oncogene, which was first identified in to thrive, gross abdominal distention, and dependence on
studies of Mennonite populations. RET encodes a tyrosine enemas without significant encopresis.21
kinase receptor, and many mutations of this gene and related
genes such as neurturin and glial cell line–derived neuro-
trophic factor (GDNF) have been identified in association with Enterocolitis
Hirschsprung disease. It remains unclear how these mutations Approximately 10% of children with Hirschsprung disease
result in aganglionosis, but there is some evidence that early present with fever, abdominal distention, and diarrhea due
neuronal cell death may be a prominent mechanism.16,17 to Hirschsprung-associated enterocolitis (HAEC), which
RET abnormalities are more commonly found in familial may be chronic, or may be severe and life-threatening. Be-
and long-segment disease. Mutations in the endothelin family cause Hirschsprung disease is generally thought of as causing
of genes, particularly endothelin-3 and the endothelin-B constipation, presentation with diarrhea may be confusing
receptor, are also commonly associated with Hirschsprung and the diagnosis may not be considered. A careful history
disease, although many of these children also have other including the failure to pass meconium and the presence of
abnormalities of neural crest–derived tissues, the most common intermittent obstructive episodes should lead to investigation
of which is Shah-Wardenberg syndrome. There is evidence for Hirschsprung disease.
from animal models that mutations in the endothelin and The etiology of HAEC is controversial. The most common
SOX-10 genes may produce early maturation or differentia- theory is that stasis caused by functional obstruction due to
tion of neural crest cells, which decreases the number of the aganglionic bowel permits bacterial overgrowth with sec-
available progenitor cells and prevents the neural crest cells ondary infection. Infectious agents such as Clostridium difficile
from migrating any further.18,19 Other genes that have been or Rotavirus have been postulated as being causative, but
associated with Hirschsprung disease include S1P1 (now there are few data to support a specific pathogen.22 There is
known as ZFHX1B), and Phox2B. some evidence implicating alterations in intestinal mucin
Hirschsprung disease is also associated with a number of production and alterations in the mucosal production of
syndromes for which the precise genetic basis of the aganglio- immunoglobulins in children with Hirschsprung-associated
nosis has not yet been elucidated. These include Trisomy-21, enterocolitis, which presumably results in loss of intestinal bar-
congenital central hypoventilation syndrome, Goldberg- rier function and allows bacterial invasion.23,24
Shprintzen syndrome, Smith-Lemli-Opitz syndrome, neurofi-
bromatosis, neuroblastoma, and a variety of other congenital Associated Conditions
anomalies.
Hirschsprung disease is associated with a variety of other con-
genital abnormalities, the presence of which should increase
the clinician’s level of suspicion (Table 101-1). These include
Diagnosis
------------------------------------------------------------------------------------------------------------------------------------------------
malrotation, genitourinary abnormalities, congenital heart dis-
ease, limb abnormalities, cleft lip and palate, hearing loss, mental
CLINICAL PRESENTATION retardation, and dysmorphic features. In addition, Hirschsprung
disease may be part of a large number of recognized syn-
Neonatal Obstruction
dromes such as trisomy 21, a variety of neurocristopathies,
Approximately 50% to 90% of children with Hirschsprung and congenital central hypoventilation syndrome.
disease present during the neonatal period with abdominal
distension, bilious vomiting, and feeding intolerance sugges-
TABLE 101-1
tive of distal intestinal obstruction. Delayed passage of meco-
Congenital Anomalies and Conditions Commonly Associated
nium beyond the first 24 hours is characteristic but is only with Hirschsprung Disease
present in approximately 90% of children with Hirschsprung
disease. In some patients cecal or appendiceal perforation may Down syndrome (trisomy 21)
be the initial event.20 Plain radiographs usually show dilated Neurocristopathy syndromes
bowel loops throughout the abdomen. The differential diag- 1. Waardenberg-Shah syndrome
nosis includes intestinal atresia, meconium ileus, meconium 2. Yemenite deaf-blind-hypopigmentation
plug syndrome, or a number of other less common conditions. 3. Piebaldism
4. Other hypopigmentation syndromes
Chronic Constipation Goldberg-Shprintzen syndrome
Smith-Lemli-Opitz syndrome
Some patients present later in childhood, or even during Multiple endocrine neoplasia 2
adulthood, with chronic constipation. This is most common Congenital central hypoventilation syndrome (Ondine curse)
among breast-fed infants, who typically develop constipation Isolated congenital anomalies
around the time of weaning. Although most children who pre- 1. Congenital heart disease
sent after the neonatal period have short-segment disease, this 2. Malrotation
history may also be found in those with longer segment or 3. Urinary tract anomalies
even total colonic involvement, particularly if the child has 4. Central nervous system anomalies
been exclusively breast-fed. Because constipation is frequently 5. Other
seen in childhood, it may be difficult to differentiate

RADIOLOGIC EVALUATION
For the neonate with a clinical picture and plain radiographs
suggesting distal neonatal bowel obstruction, the first step in
the diagnostic pathway is a water-soluble contrast enema. The
pathognomonic finding of Hirschsprung disease on contrast
enema is a transition zone between the normal and aganglio-
nic bowel (Fig. 101-1, A), although approximately 10% of
neonates with Hirschsprung disease may not have a demon-
strable radiologic transition zone.25 It is important to use
a water-soluble material because the enema may potentially
be a definitive treatment for other conditions in the differential
diagnosis such as meconium ileus and meconium plug syn-
drome. In older children an unprepped barium enema should
be done rather than a water-soluble contrast study. The ab-
sence of a transition zone is less common in this age group
but may still be present due to a short aganglionic segment.
In both neonates and older children, the most important view
is the lateral projection, in which a rectal transition zone will
be most evident (Fig. 101-1, B). Other findings on the contrast
enema that are suggestive of Hirschsprung disease include a
reversed recto-sigmoid index (Fig. 101-1, B) and retention
of contrast in the colon on a 24-hour postevacuation film.
ANORECTAL MANOMETRY
The recto-anal inhibitory reflex (RAIR) is defined as reflex re-
laxation of the internal anal sphincter in response to rectal dis-
tension and is present in normal children but absent in
children with Hirschsprung disease. The RAIR can be docu-
mented using anorectal manometry by inflating a balloon in
the rectum while simultaneously measuring the internal
sphincter pressure. Anorectal manometry is not widely avail-
able for neonates and is often operator dependent. In older
children the test is technically easier, but false-positive results
may occur due to masking of the relaxation response by con-
traction of the external sphincter, as well as artifacts created by
movement or crying. Anorectal manometry is most useful in
the evaluation of an older child with chronic constipation,
where documentation of a normal RAIR effectively rules out
Hirschsprung disease and avoids the need for a rectal biopsy.
A B
FIGURE 101-1 A, Water-soluble contrast enema demonstrating a transition zone at the splenic flexure. B, The lateral view is the most important one to
identify a low transition zone. In this case the recto-sigmoid index, consisting of the ratio of rectal diameter (R) to sigmoid diameter (S), is less than 1.0. D.
Retention of contrast on a 24-hour postevacuation film.
CHAPTER 101 HIRSCHSPRUNG DISEASE 1267
RECTAL BIOPSY
Definitive diagnosis of Hirschsprung disease is based on his-
tologic evaluation of a rectal biopsy, which remains the gold
standard diagnostic technique. The definitive finding that de-
fines Hirschsprung disease is absence of ganglion cells in the
submucosal and myenteric plexuses (Fig. 101-2, A). Most pa-
tients will also have evidence of hypertrophied nerve trunks
(Fig. 101-2, B), although this finding is not always present,
particularly in children with total colonic disease or a short
aganglionic segment. Because there is normally a paucity of
ganglion cells in the area 0.5 to 1 cm above the dentate line,
the biopsy should be taken at least 1 to 1.5 cm above it. How-
ever, a biopsy too proximal may miss a short aganglionic seg-
ment. Most surgeons use a suction biopsy technique, which is
associated with a low risk of perforation or bleeding. For chil-
dren in whom the suction biopsy yields an inadequate spec-
imen and in older children in whom the mucosa is too thick
for a suction biopsy, punch biopsies or full-thickness biopsies
provide more tissue and deeper levels.
In many centers the routine hematoxylin and eosin staining
is supplemented by staining for acetylcholinesterase, which
has a characteristic pattern in the submucosa and mucosa
in children with Hirschsprung disease (Fig. 101-2, C). Other
pathologists choose not to use acetylcholinesterase staining,
believing that it is too subjective and does not add any infor-
mation to the hematoxylin and eosin. A number of newer
stains have recently been shown to have additional value for
the diagnosis of Hirschsprung disease. The most accurate
appears to be immunochemical identification of calcitonin,
which is almost always absent in patients with Hirschsprung
disease (Fig. 101-2, D).26
Occasionally a premature infant will develop distal intesti-
nal obstruction, and the possibility of Hirschsprung disease
will be raised on the basis of clinical and radiologic parame-
ters. Early rectal biopsy in these children is not recommended
for two reasons: (1) The pathologist may have difficulty recog-
nizing ganglion cells due to their immaturity, and (2) it may be
difficult to obtain enough tissue without increasing the risk of
complications in a small premature infant. It is best in this
situation to decompress the rectum using stimulations and/or
irrigations and wait until the child is closer to term before
1268 PART VII ABDOMEN

A B C1

C2 D1 D2
FIGURE 101-2 Pathologic findings in children with Hirschsprung disease. A, Absence of ganglion cells in the myenteric plexus. B, Hypertrophied nerve
trunks. C, Cholinesterase staining in normal colon and colon affected by Hirschsprung disease. D, Calretinin staining in normal colon and colon affected by
Hirschsprung disease. (D, Courtesy Dr. Raj Kapur.)

doing the rectal biopsy. Although some surgeons believe that be administered, and a nasogastric tube should be inserted.
Hirschsprung disease is not seen in premature infants, this Children with associated abnormalities such as cardiac disease
condition has been well-documented in a number of series. or congenital central hypoventilation syndrome must be
investigated and managed before definitive surgical repair.
Children with enterocolitis or those in whom immediate
Preoperative Management surgery cannot be done for other reasons should undergo
------------------------------------------------------------------------------------------------------------------------------------------------
decompression of the colon using digital rectal stimulation,
In most cases the treatment of Hirschsprung disease is surgi- irrigations, or occasionally an emergency stoma.
cal. However, there are a number of important preoperative Once a child has been resuscitated and stabilized, opera-
interventions that must be considered before definitive surgi- tion can be done semielectively. While waiting, most children
cal intervention. The first priority is resuscitation, particularly can be discharged home on breast milk or an elemental for-
in neonates with intestinal obstruction or children presenting mula, in combination with rectal stimulations or irrigations.
with enterocolitis. In both groups, intravenous fluids and In the older child with an extremely dilated colon, operation
broad-spectrum antibiotics against enteric organisms should should be delayed until the diameter of the colon has
 CHAPTER 101 HIRSCHSPRUNG DISEASE 1269

decreased sufficiently to do a pull-through safely. This can some- the anus while preserving normal sphincter function. The
times be accomplished with weeks or months of irrigations, but most commonly performed operations are the Swenson,
some of these children may require a colostomy in order to Duhamel, and Soave procedures (Fig. 101-4), although a
adequately decompress the dilated colon (Fig. 101-3). number of other operations such as the Rebhein and State pro-
Some authors have advocated nonoperative long-term cedures have been described and are still done in some cen-
management of short-segment Hirschsprung disease using ters. Although many publications in the literature report
enemas and laxatives. Others have suggested that simple results after each of these operations, few randomized or prop-
myectomy may be adequate.27 However, these techniques erly controlled prospective studies exist. Because of this lack of
do not provide a good quality of life for most children with evidence, it is fair to say that all are acceptable alternatives and
Hirschsprung disease, and most pediatric surgeons recom- that the best operation for an individual patient is the one that
mend a pull-through procedure. the surgeon has been trained to do and does frequently.

SWENSON PROCEDURE
Pull-through Procedure for Swenson provided the first description of a surgical approach
Hirschsprung Disease to Hirschsprung disease in the late 1940s. Swenson’s goal was
------------------------------------------------------------------------------------------------------------------------------------------------
removal of the entire aganglionic colon, with an end-to-end
The goals of surgical management for Hirschsprung disease anastomosis above the anal sphincter. The operation was orig-
are to remove the aganglionic bowel and reconstruct the intes- inally done through a laparotomy, with the anastomosis being
tinal tract by bringing the normally innervated bowel down to performed from a perineal approach after eversion of the

A B
FIGURE 101-3 Value of a decompressing colostomy to decrease the size of the dilated sigmoid colon before pull-through surgery. A, Before colostomy.
B, Six months after colostomy.

A B C
FIGURE 101-4 The three most commonly performed operations for Hirschsprung disease. A, Soave. B, Swenson. C, Duhamel. þ ¼ ganglionic
bowel,  ¼ aganglionic bowel.
1270 PART VII ABDOMEN
aganglionic rectum. Safe performance of the operation re-
quires careful attention to dissection tightly on the rectal wall,
in order to avoid injury to deep pelvic nerves, vessels, and
other structures such as vagina, prostate, vas deferens, and
seminal vesicles. Despite the theoretical risks inherent in
the deep pelvic dissection, long-term outcome studies of the
Swenson procedure report excellent functional results with
respect to continence, urinary, and sexual function.28
SOAVE PROCEDURE
The Soave procedure was designed to avoid the risks of injury
to pelvic structures inherent in the Swenson procedure by
doing a submucosal endorectal dissection and placing the
pull-through bowel within a “cuff” consisting of aganglionic
muscle. In the initial description of the operation, the
pulled-through colon was left hanging out through the anus.
This exteriorized bowel was excised, and the anastomosis
done, at a second operation several weeks later. This was sub-
sequently modified by Boley, who performed the procedure in
a single stage.29 Over the years there has been controversy
regarding how long the cuff should be, as well as whether it
should be split or a segment excised. Despite claims by some
authors that the Soave procedure is more likely to result in
long-term issues with constipation due to incomplete excision
of the aganglionic rectum,30 most late follow-up studies have
reported similar outcomes to that seen with the Swenson
procedure.31
DUHAMEL PROCEDURE
The Duhamel procedure involves bringing the normal colon
down through the bloodless plane between the rectum and
the sacrum and joining the two walls to create a new lumen,
which was aganglionic anteriorly and normally innervated
posteriorly. In the initial description, two Kocher clamps were
used to join the walls and were left in for a week. More
recently, surgical staplers were used instead. The Duhamel
procedure has several potential advantages over the Swenson
or Soave procedures. It is believed to be easier and safer, with
less pelvic dissection than the other two operations; it has a
large anastomosis, which decreases the risk of anastomotic
stricture; and the presence of a “reservoir” makes it appealing
for children with longer aganglionic segments.
A B
FIGURE 101-5 Laparoscopic pull-through. A, Confirmation of the pathologic transition zone. B, Laparoscopic view of the completed pull-through
from above. (Courtesy Dr. Steve Rothenberg.)
Role of Colostomy
------------------------------------------------------------------------------------------------------------------------------------------------
Swenson’s initial operation was described as a one-stage
procedure, but relatively high incidence of stricture, leak, and
other adverse outcomes led him and others to recommend a
routine preliminary colostomy, followed by a period of growth
and a subsequent reconstructive operation.32 This approach
became surgical dogma, which was reinforced by the fact that
many children with Hirschsprung disease presented late with
malnutrition and dilated colon, so a colostomy was a life-
saving procedure. In the 1980s, however, a number of surgeons
reported series of single-stage pull-through procedures even in
small infants.33,34 Over the next 10 to 15 years, one-stage
operations became increasingly popular and many reports
documented the safety of this approach, suggesting that a
single-stage procedure avoids the known morbidity of stomas
in infants and is also more cost-effective.35–37 It is important
to remember, however, that a stoma may still be indicated
for children with severe enterocolitis, perforation, malnutri-
tion, or massively dilated proximal bowel, as well as in situa-
tions where there is inadequate pathology support to reliably
identify the transition zone on frozen section.
Minimal Access Approaches
------------------------------------------------------------------------------------------------------------------------------------------------
LAPAROSCOPIC PULL-THROUGH
With the advent of laparoscopic surgery in the late 1980s,
minimal access techniques became increasingly applied to
pediatric surgical diseases. The first minimal approach to
pull-through surgery for Hirschsprung disease was described
by Georgeson in 1995,38 who described a laparoscopic pull-
through for Hirschsprung disease, involving laparoscopic bi-
opsy to identify the transition zone, laparoscopic mobilization
of the rectum below the peritoneal reflection, and a short
mucosal dissection through a perineal approach (Fig. 101-5).
The rectum is then prolapsed through the anus, and the anas-
tomosis is done from below. This procedure has been
associated with a shorter hospital time, and both early and mid-
term results appear to be equivalent to those reported for the
open procedures.39 Laparoscopic approaches have been also
described for the Duhamel and Swenson operations, with
excellent short-term results reported.40,41
 CHAPTER 101 HIRSCHSPRUNG DISEASE 1271

TRANSANAL (PERINEAL) PULL-THROUGH

The transanal pull-through procedure uses the same mucosal
dissection from below as the Georgeson operation, but with-
out laparoscopic mobilization of the rectum. The mucosal in-
cision is made 0.5 to 1 cm above the dentate line, depending
on the size of the child, and the mucosa is stripped from the
underlying muscle as in the Soave operation. The rectal mus-
cle is then incised circumferentially, and the dissection is con-
tinued on the rectal wall, dividing the vessels as they enter the
rectum. The entire rectum and part of the sigmoid colon can
be delivered through the anus. When the transition zone is
reached, the anastomosis is done from below (Fig. 101-6).
In patients with a more proximal transition zone (usually
above the proximal sigmoid colon), laparoscopy or a small
umbilical incision can be used to mobilize the left colon
and/or splenic flexure to achieve adequate length. A transanal
approach can also be used if the patient has already had a co-
lostomy, by using the stoma as the end of the pull-through
bowel and performing the rectal excision using the transanal
technique.
The transanal approach has a low complication rate, re-
quires minimal analgesia, and is associated with early feeding
and discharge.42–45 Although there have not been any studies
comparing the transanal and laparoscopic approaches, the
transanal pull-through can be done by any pediatric surgeon,
including those without laparoscopic skills, and by pediatric
surgeons in parts of the world where access to appropriately
miniaturized laparoscopic equipment is limited.
A number of ongoing controversies surround the transanal
pull-through. The first is whether the pathologic transition
zone should be defined before beginning the anal dissection.
This was not done in the early descriptions of the operation
and continues to be omitted by many surgeons. The main
rationale for this practice is the known inaccuracy of the
contrast enema in predicting the level of aganglionosis, with
approximately 8% of children who have a rectosigmoid tran-
sition zone on contrast study having a more proximal transi-
tion zone on histology.46 This step is particularly important for
surgeons who do a different operation for long-segment dis-
ease than they do for rectosigmoid disease. The preliminary
biopsy can be done using a laparoscopic approach, or through
a small umbilical incision, both of which can also be used to
mobilize the splenic flexure in children with higher transition
zones.47 The advantage of the umbilical approach is that it can
be done by any surgeon, anywhere in the world, and does not
require laparoscopic skills or equipment. Evidence would
suggest that a preliminary biopsy to determine the pathologic
transition zone does not have a deleterious effect on post-
operative outcomes such as time to feeding, pain, or length
of hospital stay.45,48
There is also controversy about whether the transanal pull-
through is best done in the prone or supine position.49 The
prone position provides excellent visualization and is familiar
to most pediatric surgeons because of their experience with it
in the repair of anorectal malformations. The supine position
has the advantage of access to the peritoneal cavity for initial
colonic biopsy or for mobilization of the colon or a stoma if
necessary. Finally, there is controversy about the length of
the rectal cuff. The initial description of the transanal pull-
through involved a long cuff, with a submucosal dissection
extending into the peritoneal cavity. Many surgeons continue
to do the operation this way, and most advocate division of the
cuff to prevent narrowing. Other surgeons have modified the
procedure by doing a short submucosal dissection for a few
centimeters, and others have abandoned the submucosal
dissection entirely and do what is essentially a transanal

A B C

D E
FIGURE 101-6 The transanal Soave pull-through. A, An umbilical incision is used for a preliminary biopsy. A Heger dilator is used to push the sigmoid
into the umbilical incision. B, Eversion sutures are placed, and a nasal speculum is used to provide exposure to the anal canal. A circumferential incision is made
5 mm from the dentate line. C, The submucosal dissection is carried 2 to 3 cm. D, Once the muscle cuff has been divided circumferentially, the dissection
is carried proximally, staying right on the colonic wall. E, The bowel is divided at least 2 cm above the biopsy showing ganglion cells, and the anastomosis
is performed. Care must be taken to do the anastomosis to the rectal mucosa, not to the transitional epithelium, or normal sensation will be lost and the risk
of incontinence will be increased.
1272 PART VII ABDOMEN

Swenson procedure.50 The advantage of a shorter cuff is a Once the level of aganglionosis has been identified, most
lower rate of narrowing and potentially a lower risk of surgeons create a stoma, wait for permanent sections, and
postoperative obstructive symptoms and enterocolitis.48 do a definitive reconstructive procedure at a later time. Al-
though primary pull-through without ileostomy for total co-
lonic disease has been reported, this approach requires a
Surgical Approach to Long- high degree of confidence in the pathologist because it re-
quires doing a total colectomy on the basis of frozen sections
Segment Hirschsprung Disease alone. In addition, many surgeons believe that the results of
------------------------------------------------------------------------------------------------------------------------------------------------
pull-through surgery are better once the stool has thickened,
Long-segment Hirschsprung disease is usually defined as a which usually occurs in the first few months of life.
transition zone that is proximal to the midtransverse colon. Three types of operations are available for reconstruction in
The most common is total colonic aganglionosis, which usu- children with long-segment Hirschsprung disease: straight
ally also includes some of the distal ileum. In rare cases most of pull-through, colon patch, and J-pouch construction. Straight
or the entire small bowel is aganglionic. Long-segment disease pull-through procedures involve bringing the normally inner-
is more likely to be associated with a positive family history51 vated ileum to just above the anal sphincter, using any one of
and is more likely to be diagnosed prenatally.52 Contrast the standard techniques (Swenson, Duhamel, or Soave). Co-
enema typically shows a shortened, relatively narrow colon lon patch procedures involve a side-to-side anastomosis be-
(“question mark colon”) (Fig. 101-7),53 and there may also tween normally innervated small bowel and aganglionic
be a transition zone in the small bowel. The rectal biopsy colon, using the small bowel for motility and the colon as a
shows absence of ganglion cells, but in many cases there are reservoir for storage of stool and absorption of water. The
no hypertrophic nerves or abnormalities of acetylcholinester- Martin procedure consists of a Duhamel reconstruction that ex-
ase staining. tends proximally to involve the entire left colon (Fig. 101-8, A).
Early resuscitation and management is similar to that de- Kimura, using the rationale that the right colon is better at water
scribed for standard Hirschsprung disease. Sequential colonic absorption than the left colon, advocated a staged procedure, in
biopsies are done looking for ganglion cells on frozen section. which the right colon is anastomosed side-to-side to the ileum.
These can be done through a standard laparotomy, laparosco- The “ileo-colon” is then disconnected from the right colonic
pically, or through an umbilical incision, which in a newborn blood supply after several months and anastomosed above the
can be used to access all parts of the colon. Traditionally, many anal sphincter (Fig. 101-8, B). The J-pouch procedure is done
surgeons started with an appendectomy, assuming that lack of commonly for children and adults with ulcerative colitis and
ganglion cells in the appendix would be diagnostic of total familial polyposis syndrome, and some pediatric surgeons
colonic disease. However, this may result in a false-positive have reported the use of this operation for children with
diagnosis of total colonic Hirschsprung disease because there long-segment Hirschsprung disease.55
may be a paucity of ganglion cells in the appendix in children There are no prospective or well-controlled series reporting
with shorter segment disease.54 long-term results of surgery for long-segment Hirschsprung
disease. Although the colon patch procedures theoretically
result in decreased stool output due to better water absorp-
tion, the aganglionic colon gradually tends to dilate and many
of these patients develop severe enterocolitis, which requires
removal of the patch or a permanent stoma. Children under-
going straight pull-through tend to experience gradually
decreasing stool frequency over time, with an acceptable
quality of life.56–58
Near-Total Intestinal Aganglionosis
Rarely, almost the entire intestinal tract of a patient is agangli-
onic, usually leaving 10 to 40 cm of normally innervated jeju-
num. In most of these cases, there is not enough functional
small bowel to support enteral nutrition and intestinal failure
results. These children require total parenteral nutrition from
birth, a situation that has been associated with a high risk of
mortality from liver failure. The surgical approach at the time
of the first laparotomy is to determine the extent of aganglio-
nosis on the basis of frozen sections and to bring out a stoma at
the most distal point that has normally innervated bowel.
Some surgeons prefer to bring out a more distal stoma, but this
approach may increase the risk of chronic intestinal obstruc-
tion and bacterial overgrowth. A central venous catheter
should be inserted for parenteral nutrition, and a gastrostomy
should be considered for continuous “trophic” feeding of
FIGURE 101-7 Contrast enema in a child with total colonic Hirschsprung
breast milk or elemental formula.
disease. There is no transition zone in the colon, and the colon is foreshor- The management of these children is similar to the manage-
tened with a “question-mark” configuration. ment of any child with intestinal failure.59 Strict attention to
 CHAPTER 101 HIRSCHSPRUNG DISEASE 1273

C
FIGURE 101-8 Operations for long-segment Hirschsprung disease. A, Martin procedure. B and C, Kimura procedure.

prevention of sepsis, treatment of bacterial overgrowth, use of
trophic feeds, and prevention of TPN-related cholestasis are
all extremely important. Recent experience with omega-3
lipids has resulted in encouraging trends toward prevention
and treatment of this problem.60
A number of surgical options are available for children with
near-total aganglionosis.61 For children who develop signifi-
cant proximal dilatation of the normally innervated bowel,
tapering, imbrication, or bowel-lengthening procedures
such as the Bianchi or serial transverse enteroplasty (STEP)
1274 PART VII ABDOMEN

procedure may be used.62,63 Zeigler has popularized a tech- OBSTRUCTIVE SYMPTOMS

nique known as “myectomy-myotomy,” in which a length of
aganglionic small bowel distal to the transition zone un- There are a range of obstructive symptoms that can be seen
dergoes myectomy.64 Although a few successful cases using after a pull-through. Abdominal distension, bloating, vomit-
this technique have been reported, most surgeons have not ing, or ongoing severe constipation may be present immedi-
found it to be successful and have noted high rates of postop- ately after surgery or may develop later after an initial
erative complications. For children with ongoing liver failure, period of normal bowel function. There are five major reasons
small bowel or combined small bowel-liver transplantation for persistent obstructive symptoms following a pull-through:
may offer the only chance for survival. A recent report from mechanical obstruction, recurrent or acquired aganglionosis,
Paris documented extremely good results in 12 patients, many disordered motility in the proximal colon or small bowel,
of whom underwent successful pull-through surgery follow- internal sphincter achalasia, or functional megacolon caused
ing their intestinal transplant.65 by stool-holding behavior (Table 101-2). The clinician will
have much greater success in managing these difficult patients
if an organized approach to this problem is taken. One
Postoperative Care
------------------------------------------------------------------------------------------------------------------------------------------------
proposed algorithm is shown in Figure 101-9.71
Mechanical Obstruction
Most children undergoing a laparoscopic or transanal pull-
through for standard Hirschsprung disease can be fed imme- The most common cause of mechanical obstruction after a
diately, and most can be discharged within 24 to 48 hours. pull-through is a stricture, which usually occurs after a Swen-
The anastomosis should be calibrated with an appropriately son or Soave procedure (Fig. 101-10, A). Patients undergoing
sized dilator or finger 1 to 2 weeks after the procedure. Al- a Duhamel procedure may have a retained “spur” consisting of
though many surgeons instruct the parents to dilate the anas- the anterior aganglionic bowel, which may fill with stool and
tomosis on a daily basis, others have found it to be obstruct the pulled-through bowel (Fig. 101-10, B). In other
unnecessary in most cases and instead perform weekly cali- cases, there may be obstruction secondary to a twist in the
bration for a period of 4 to 6 weeks. It is important for the pulled-through bowel (Fig. 101-10, C) or narrowing due to
parents to protect the buttocks with a barrier cream because a long muscular cuff in children who have had a Soave
at least 50% of children will have frequent stools and peri- procedure.
neal skin breakdown postoperatively. Fortunately, this prob- Obstruction can be identified using a combination of dig-
lem tends to resolve over time. ital rectal examination and a barium enema. Initial manage-
As with any operation, children undergoing a pull-through ment of anastomotic stricture consists of repeated dilatation
may develop a wound infection or intra-abdominal bleeding. using a finger, dilator, or radially dilating balloon. Some au-
In addition, anastomotic complications such as leak or stric- thors have advocated innovative techniques for recalcitrant
ture may occur. Intestinal perforation can occur at a proximal strictures including antegrade dilatation over a string using
biopsy site due to back pressure from anal sphincter spasm or Tucker dilators72 and the use of intralesional steroid.73 In
due to unrecognized cautery injury. Bowel obstruction can re- some cases the stricture cannot be successfully dilated, and
sult from intra-abdominal adhesions, a twist in the pull- revision of the pull-through is necessary. This is best done
through bowel, or a muscular cuff that has rolled down and using the Duhamel technique, although other operations have
constricted the pull-through bowel. In rare cases, rectovesical also been advocated.74–76 Duhamel spurs can be resected from
or rectovaginal fistulas have developed after pull-through above or managed by extending the staple line from below,
surgery. Close monitoring for and early treatment of these with or without laparoscopic visualization. Twisted pull-
complications is imperative. In addition, children with throughs and narrow muscular cuffs usually require surgical
Hirschsprung disease can develop enterocolitis, even in the intervention, typically a repeat pull-through. In some cases,
early postoperative period. The family and the primary care a muscular cuff can be divided laparoscopically without
physician should be educated about the signs and symptoms having to re-do the entire pull-through.
of enterocolitis, and the family must be told to bring the child
to the hospital if there are any signs suggestive of this problem Persistent or Acquired Aganglionosis
because children can become very sick and even die from This rare problem may be due to pathologist error,77 a tran-
enterocolitis.66 sition zone pull-through,78 or ganglion cell loss after a
pull-through.79 Repeat rectal biopsy, above the previous anas-
tomosis (it must be posterior in the case of an initial Duhamel
Long-Term Outcomes
------------------------------------------------------------------------------------------------------------------------------------------------
procedure), should be done to determine whether there are
Long-term problems in children with Hirschsprung disease
include ongoing obstructive symptoms, soiling, and enteroco- TABLE 101-2
litis.67 Quite often an individual child may have a combination Causes of Obstructive Symptoms Following Surgery
of problems. Although early reports suggested that long-term for Hirschsprung Disease
issues were rare after surgical treatment of Hirschsprung dis- Mechanical obstruction
ease,68 it is now clear that these complications are more com- Recurrent or residual aganglionosis
mon than previously recognized.31,69,70 It is important for the Motility disorder involving the ganglionated bowel
surgeon to follow these children closely, at least until they are Internal anal sphincter achalasia
through the toilet training process, in order to identify and Functional megacolon (stool-holding behavior)
provide early treatment for these problems.
 CHAPTER 101 HIRSCHSPRUNG DISEASE 1275

Physical exam and barium enema

No stricture Stricture

Rectal biopsy
Dilate or redo
pull-through
Ganglion cells present
No ganglion cells

Motility workup
Redo pull-through

Normal Abnormal focal Abnormal generalized

Try botox Resect

Bowel regimen
or stoma

Clinical response No clinical response

Repeat botox or
myectomy

FIGURE 101-9 Algorithm for the investigation and management of the child with obstructive symptoms following a pull-through.

A B C
FIGURE 101-10 Causes of mechanical obstruction after a pull-through. A, Stricture following a Soave procedure. B, Anterior aganglionic “spur” following
a Duhamel procedure. C, Twisted transanal pull-through.

normal ganglion cells present in all patients with persistent
obstructive symptoms after surgery. The pathology from the
original operation should be reviewed to ensure that there
was normal innervation at the proximal margin, and in some
cases further sections should be done circumferentially from
the resection margin because the transition zone is often asym-
metrical in children with Hirschsprung disease.80 The best
treatment for persistent or acquired aganglionosis in most
cases is a repeat pull-through, which can be done using either
a Soave or Duhamel approach.75
Motility Disorder Children with Hirschsprung disease
often have associated motility disorders including an in-
creased incidence of gastroesophageal reflux and delayed
gastric emptying,81 small bowel dysmotility, and disordered
colonic motility. Some cases are more focal, usually involving
the left colon. In some cases the disordered motility may be
associated with histological abnormalities such as intestinal
neuronal dysplasia (discussed in greater detail later).
In children who have been shown not to have a mechanical
obstruction and who have normal ganglion cells on rectal
1276 PART VII ABDOMEN
biopsy, investigations for motility disorders should be under-
taken. This can include a radiologic shape study, radionuclide
colon transit study,82 colonic manometry,83 and laparoscopic
biopsies looking for evidence of intestinal neuronal dyspla-
sia.84 If a focal abnormality is found, consideration should
be given to resection and repeat pull-through using normal
bowel. If the abnormality is diffuse, the appropriate treatment
is bowel management and the use of prokinetic agents. Some
children with particularly dysmotile colon will benefit from
placement of a cecostomy for antegrade colonic enemas.85
Internal Sphincter Achalasia This term refers to the lack of
a normal RAIR that is present in all children with Hirsch-
sprung disease (as described earlier in “Diagnosis”). It is
unclear why only some children develop obstructive symp-
toms from this nonrelaxation, while others function normally
in the postoperative period. It is also unclear why most chil-
dren eventually “grow out” of this problem over time, usually
by the age of 5 years. Internal sphincter achalasia is a diagnosis
of exclusion, which is made after ruling out mechanical ob-
struction, aganglionosis, and dysmotility. The diagnosis can
be confirmed by demonstrating a clinical response to intra-
sphincteric botulinum toxin.86 However, the response to bot-
ulinum toxin is not related to the absolute value of the internal
anal sphincter pressure (i.e., patients with a higher resting
pressure are not necessarily more likely to benefit from botu-
linum toxin).
The standard treatment of internal sphincter achalasia has
been internal sphincterotomy or myectomy,87,88 but because
this problem tends to resolve on its own in most children
and there is concern about sphincter-cutting operations
exacerbating future soiling issues, we prefer to use “che-
mical sphincterotomy” with intrasphincteric botulinum
toxin.86,89,90 In many cases repeated injection of botulinum
toxin or applications of nitroglycerine paste or topical nifedi-
pine are necessary while waiting for resolution of the problem.
Functional Megacolon Functional megacolon is the result
of stool-holding behavior, a common cause of constipation
that some authors claim affects up to half of normal children
at some time during their first few years of life.91 This
condition is probably even more common in children with
Hirschsprung disease because of their predisposition to con-
stipation, which leads to hard painful stools, withholding be-
havior, and a resulting vicious cycle.92 The treatment for this
problem is a bowel management regimen consisting of
laxatives, enemas, and behavior modification including
support for the child and family. In some severe cases of
obstructive symptoms, the child may be best served by use
of a cecostomy and administration of antegrade enemas, or
even by the creation of a proximal stoma. In many cases the
cecostomy or stoma can ultimately be reversed when the child
reaches adolescence.
Fecal Soiling
There are three broad causes of soiling after a pull-through:
abnormal sphincter function, abnormal sensation, or
“pseudo-incontinence” related to abnormal rectal function
or obstipation (Table 101-3). Abnormal sphincter function
may be due to sphincter injury during the pull-through or
to a previous myectomy or sphincterotomy and can usually
be identified using anorectal manometry. Two forms of
TABLE 101-3
Causes of Soiling Following Surgery for Hirschsprung Disease
Abnormal sensation
1. Inability to feel rectal distension
2. Loss of transitional epithelium
Abnormal sphincter function
“Pseudo-incontinence”
1. Associated with severe constipation
2. Associated with hyperperistalsis of the pulled-through bowel
abnormal sensation exist. The first is lack of sensation of a
full rectum, which is also identifiable using anorectal manom-
etry by expanding a balloon in the rectum and asking the
child to state when he can feel it. The other type of sensation
that may be abnormal is the ability to detect the difference
between gas and stool, which is dependent on intact transi-
tional epithelium in the anal canal. This sensation may be im-
paired if the anastomosis is done too low and the transitional
epithelium is damaged. This problem is usually evident on
simple physical examination. Neither sphincter weakness
nor abnormal sensation is amenable to a surgical solution,
and most of these children are best managed using a bowel
routine that may include a constipating diet, rectal enemas,
or antegrade enemas through a cecostomy. Biofeedback train-
ing has been advocated, especially for those children with
sphincter weakness. In some cases the child is best served
by a colostomy.
If both the sphincter and sensation are intact, the
most common cause of soiling after a pull-through is “pseudo-
incontinence.”93 Some patients have severe obstipation with a
massively distended rectum and develop overflow of liquid
stool around the fecal mass. Others simply leak small amounts
of stool through the day, creating “skid marks” in the under-
wear on a constant basis. Other children suffer from hyper-
peristalsis of the pulled-through bowel, which results in
inability of the anal sphincter to achieve control despite
normal sphincter function.83
Successful management depends on a clear understanding
of the underlying basis for the soiling, which requires a clear
history and physical examination, as well as investigations
such as abdominal radiograph, barium enema, anorectal ma-
nometry, and in some cases colonic manometry. Children with
severe constipation will benefit from laxative therapy. How-
ever, if the sphincter or sensation, or both, are inadequate,
passive laxatives such as lactulose or PEG 3300 will make
the problem worse and the child should instead be treated
with stimulant laxatives such as senna or enemas. On the other
hand, children with stool-holding behavior who have a nor-
mal sphincter and sensation will often experience exacer-
bation of the behavioral problem by rectal enemas or any
other kind of anal manipulation. Children without constipa-
tion who have hyperperistalsis of the pulled-through bowel or
abnormal sphincter function or sensation will benefit from a
constipating diet and medications such as loperamide. Chil-
dren with slow transit constipation or stool-holding behavior,
on the other hand, will benefit from a high-fiber diet and
passive laxative therapy. The treatment of soiling must be
based on a clear understanding of the child’s underlying
problem.

Enterocolitis
Enterocolitis may be present both before and after surgical
correction of the disease, and it can be severe or life threaten-
ing. HAEC is more common in children diagnosed at a youn-
ger age,94 those with longer segment disease, and those with
trisomy 21. The clinical features of HAEC are generally agreed
on and include fever, abdominal distention, diarrhea, elevated
white blood cell count, and evidence of intestinal edema on
abdominal radiograph. Because there is overlap between
HAEC and other conditions such as obstructive symptoms
and gastroenteritis, there has been confusion in the literature
as to the exact definition and the true incidence of the condi-
tion. A recently developed HAEC score may be useful in the
future in both the clinical setting and in research into this area
(Table 101-4).95
The treatment of postoperative HAEC involves nasogastric
drainage, intravenous fluids, broad-spectrum antibiotics, and
decompression of the rectum and colon using rectal stimulation
or irrigations. The risk of HAEC can be minimized by using pre-
ventive measures such as routine irrigations96 or chronic ad-
ministration of metronidazole or probiotic agents, particularly
in those who are thought to be at higher risk for this complica-
tion on the basis of clinical or histologic grounds. Because en-
terocolitis is the most common cause of death in children with
Hirschsprung disease and can occur postoperatively even in
children who did not have it preoperatively, it is extremely im-
portant that the surgeon educate the family about the risk of this
complication and urge early return to the hospital if the child
should develop any concerning symptoms.66
Long-Term Outcomes
Despite the relatively common occurrence of postoperative
problems, most children with Hirschsprung disease overcome
these issues and do well. Obstructive symptoms, soiling, and
TABLE 101-4
Hirschsprung-Associated Enterocolitis (HAEC) Score*
History
Diarrhea with explosive stool
Diarrhea with foul-smelling stool
Diarrhea with bloody stool
Previous history of enterocolitis
Physical examination
Explosive discharge of gas and stool on rectal examination
Distended abdomen
Decreased peripheral perfusion
Lethargy
Fever
Radiology
Multiple air-fluid levels
Dilated loops of bowel
Sawtooth appearance with irregular mucosal lining
Cutoff sign in recto-sigmoid with absence of distal air
Pneumatosis
Laboratory
Leukocytosis
Shift to left
*A score of 10 or higher was associated with a positive diagnosis of HAEC by an
international panel of experts.
CHAPTER 101 HIRSCHSPRUNG DISEASE 1277
enterocolitis, in the absence of an ongoing source of obstruc-
tion, usually resolve after the first 5 years of life. Studies of
teenagers and adults with Hirschsprung disease suggest that
sexual function, social satisfaction, and quality of life all
appear to be normal in the vast majority of patients once they
reach their late teens.69,97
Several populations of children have less optimistic out-
comes. Children with long-segment disease appear to have
a higher risk of enterocolitis, incontinence, and dehydration
than children with shorter-segment disease. Children with
Hirschsprung disease associated with Down syndrome have
a greater risk of enterocolitis and incontinence.98,99 Finally,
prognosis may be poor in children with other types of comor-
bidity such as those with congenital central hypoventilation
syndrome, congenital heart disease, and syndromes that are
associated with mental retardation or other forms of disability.
“Variant” Hirschsprung Disease
------------------------------------------------------------------------------------------------------------------------------------------------
Some children present with signs and symptoms suggestive of
Hirschsprung disease but have ganglion cells present on rectal
biopsy.100 There is a significant amount of controversy sur-
rounding the definitions and features of many of these condi-
tions,101 and in some cases their existence has even been
called into question.
INTESTINAL NEURONAL DYSPLASIA
This condition was first described by Meier-Ruge in 1971. Two
types are usually described.102 Type A is less common and is
characterized by diminished or absent sympathetic innerva-
tion of the myenteric and submucosal plexuses, as well as hy-
perplasia of the myenteric plexus. Type B consists of dysplasia
of the submucous plexus with thickened nerve fibers and
giant ganglia, increased acetylcholinesterase staining, and
identification of ectopic ganglion cells in the lamina propria.
Type B can occur on its own or can be present in the nonagan-
glionic bowel in children who also have Hirschsprung disease.
2 In addition, intestinal neuronal dysplasia may be either diffuse
2 or focal. The reported incidence of IND varies significantly
1 from one center to another, largely due to differences in
1 definition of the condition.
Despite multiple publications on the topic of IND, this
2 topic still stimulates controversy among pediatric surgeons
2 and pediatric pathologists.103 The diagnostic criteria have
1 changed over time, and there is disagreement among pathol-
1 ogists about the diagnosis both in general terms and with re-
1 spect to individual patients.104 Sophisticated histologic
techniques including special stains and the use of thick sec-
1 tions are often believed to be necessary for an accurate diag-
1 nosis.105 In addition, there is some evidence that the
1 histologic finding of IND may in some cases be secondary
1 to chronic obstruction rather than the cause of it, and in many
1 cases there may not be good correlation between the histologic
finding of IND and the motility function of the bowel.106
1 Hypoganglionosis
1
This is a rare form of dysganglionosis, which is characterized by
sparse and small ganglia, usually in the distal bowel, often as-
sociated with abnormalities in acetylcholinesterase distribution.
1278 PART VII ABDOMEN
The appropriate treatment is to resect the abnormal colon and
perform a pull-through procedure, much as one would do for
a child with Hirschsprung disease.107 It is important to differ-
entiate this condition from immature ganglia, which is seen in
preterm children who present with a picture of distal intesti-
nal obstruction resulting from underdeveloped colonic motil-
ity. The colonic motility is self-limited and should not be
treated surgically.108
Internal Sphincter Achalasia
Some children have normal ganglion cells on rectal biopsy but
lack the RAIR on anorectal manometry. These children will
sometimes develop obstructive symptoms or severe constipa-
tion that mimics Hirschsprung disease. Similarly to the situa-
tion mentioned previously in which obstructive symptoms
continue after surgery for Hirschsprung disease, this condi-
tion has been termed internal sphincter achalasia.109 The diag-
nosis is made using anorectal manometry and rectal biopsy.
The initial treatment is a bowel management regimen, consisting
of diet, laxatives, and enemas or irrigations. If this is unsuccess-
ful, many surgeons have advocated the use of anal sphincter
myectomy.110,111 Because the constipation associated with this
condition usually improves over the first 5 years of life, the
same rationale has been used to advocate temporary or revers-
ible sphincter-relaxing measures such as botulinum toxin,112
nitroglycerine paste,113 or topical nifedipine.
Ultrashort-Segment Hirschsprung Disease
There is much confusion in the literature regarding this
condition and how it is defined. Some authors use this term to
describe children with normal ganglion cells on rectal biopsy,
but with absence of the RAIR (which is synonymous
with the definition of internal sphincter achalasia). We prefer
to reserve it for children who have a documented aganglionic
segment of less than 1 to 2 cm. In children with thiscondition, the
findings of hypertrophic nerves and abnormal cholinesterase
staining may be absent.114 The treatment of ultrashort-segment
Hirschsprung disease is controversial. Some authors advocate
simple anal sphincter myectomy,115,116 and some prefer excision
of the aganglionic segment and pull-through reconstruction.
Desmosis coli
This is a condition described by Meier-Ruge characterized by
total or focal lack of the connective tissue net of the circular
and longitudinal muscles and the connective tissue layer of
the myenteric plexus, without any abnormality of the enteric
nervous system.117 Patients with this condition present with
chronic constipation. In one family Hirschsprung disease
and desmosis coli coexisted,118 although in most cases they
are completely separate entities.
The complete reference list is available online at www.
expertconsult.com.