1806  Part XVIII  ◆  The Digestive System
Table 332-1 Findings in Pseudoobstruction
Chapter 332  Esophageal motility
Motility Disorders and
Hirschsprung Disease
332.1  Chronic Intestinal Pseudoobstruction
Kristin N. Fiorino and Chris A. Liacouras
Chronic intestinal pseudoobstruction comprises a group of disorders
characterized as a motility disorder with a primary defect of impaired
peristalsis; symptoms are consistent with intestinal obstruction in the
absence of mechanical obstruction. The natural history of pseudoob-
struction is that of a primary progressive disorder, although there are
occasional cases of secondary pseudoobstruction caused by conditions
that can transiently or permanently alter bowel motility. The most
common cause of acute pseudoobstruction is Ogilvie syndrome (acute
pseudoobstruction of the colon). Pseudoobstruction represents a wide
spectrum of pathologic disorders from abnormal myoelectric activity
to abnormalities of the nerves (intestinal neuropathy) or musculature
(intestinal myopathy) of the gut. The organs involved can include the
entire gastrointestinal tract or be limited to certain components,
although almost always include the small bowel. The distinctive patho-
logic abnormalities are considered together because of their clinical
similarities.
Most congenital forms of pseudoobstruction occur sporadically,
although autosomal dominant, autosomal recessive, X-linked, and
familial patterns of inheritance have been identified. Patients with
autosomal dominant forms of pseudoobstruction have variable expres-
sions of the disease. Acquired pseudoobstruction can follow episodes
of acute gastroenteritis, presumably resulting in injury to the myenteric
plexus.
In congenital pseudoobstruction, abnormalities of the muscle or
nerves can be demonstrated in the majority of cases. In myopathies, the
smooth muscle is involved, in which the outer longitudinal muscle layer
is replaced by fibrous material. The enteric nervous system is usually
altered in neuropathies and may involve disorganized ganglia, hypo-
ganglionosis, or hyperganglionosis. Abnormalities in the interstitial
cells of Cajal, the intestinal pacemaker, are classified as mesenchymopa-
thies. In others, mitochondrial defects have been identified. Genetic
defects have been identified in the transcription factor SOX10 and the
DNA polymerase gamma gene (POLG) in mitochondriopathies.
CLINICAL MANIFESTATIONS
More than half the children with congenital pseudoobstruction expe-
rience symptoms in the 1st few mo of life. Two-thirds of the infants
presenting in the 1st few days of life are born prematurely, and approx-
imately 40% have malrotation of the intestine. In 75% of all affected
children, symptoms occur in the 1st yr of life, while the remainder
are usually symptomatic within the next several years. The most
common symptoms are abdominal distention and vomiting, which
are present in 75% of affected infants. Constipation, growth failure,
and abdominal pain occur in approximately 60% of patients, and
diarrhea in 30-40%. The symptoms wax and wane in the majority
of the patients; poor nutrition, psychologic stress, and intercurrent
illness tend to exacerbate symptoms. Urinary tract and bladder
involvement occurs in 80% of children with myopathic pseudoob-
struction and in 20% of those with neuropathic disease. Symptoms can
manifest as recurrent urinary tract infection, megacystis, or obstruc-
tive symptoms.
Downloaded from ClinicalKey.com at Universitas Kristen Duta Wacana January 20, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
GI SEGMENT FINDINGS*
Abnormalities in approximately half of CIPO,
although in some series up to 85%
demonstrate abnormalities
Decreased LES pressure
Failure of LES relaxation
Esophageal body: low-amplitude waves, poor
propagation, tertiary waves, retrograde
peristalsis, occasionally aperistalsis
Gastric emptying May be delayed
EGG Tachygastria or bradygastria may be seen
ADM Postprandial antral hypomotility is seen and
correlates with delayed gastric emptying
Myopathic subtype: low-amplitude
contractions, <10-20 mm Hg
Neuropathic subtype: contractions are
uncoordinated, disorganized
Absence of fed response
Fasting MMC is absent, or MMC is
abnormally propagated
Colonic Absence of gastrocolic reflex because there
is no increased motility in response to a
meal
ARM Normal rectoanal inhibitory reflex
*Findings can vary according to the segment(s) of the GI tract that are involved.
ADM, Antroduodenal manometry; ARM, anorectal manometry; CIPO, chronic
intestinal pseudoobstruction; EGG, electrogastrography; GI, gastrointestinal;
LES, lower esophageal sphincter; MMC, migrating motor complex.
From Steffen R: Gastrointestinal motility. In Wyllie R, Hyams JS, Kay M,
editors: Pediatric gastrointestinal and liver disease, ed 3, Philadelphia, 2006,
WB Saunders, p. 66.
DIAGNOSIS
The diagnosis of pseudoobstruction is based on the presence of com-
patible symptoms in the absence of mechanical obstruction. Plain
abdominal radiographs demonstrate air–fluid levels in the intestine.
Neonates with evidence of obstruction at birth may have a microcolon.
Contrast studies demonstrate slow passage of barium; water-soluble
agents should be considered. Esophageal motility is abnormal in about
half the patients. Antroduodenal (small intestinal) motility and gastric
emptying studies have abnormal results if the upper gut is involved
(Table 332-1). Manometric evidence of a normal migrating motor
complex and postprandial activity should redirect the diagnostic evalu-
ation. Anorectal motility is normal and differentiates pseudoobstruc-
tion from Hirschsprung disease. Full-thickness intestinal biopsy might
show involvement of the muscle layers or abnormalities of the intrinsic
intestinal nervous system.
The differential diagnosis is broad and includes such etiologies as
Hirschsprung disease, mitochondrial neurogastrointestinal encephalo-
myopathy, other causes of mechanical obstruction, psychogenic
constipation, neurogenic bladder, and superior mesenteric artery
syndrome. Secondary causes of ileus or pseudoobstruction, such as
hypothyroidism, opiates, scleroderma, Chagas disease, hypokalemia,
diabetic neuropathy, amyloidosis, porphyria, angioneurotic edema,
mitochondrial disorders, and radiation, must be excluded.
TREATMENT
Nutritional support is the mainstay of treatment for pseudoobstruc-
tion. Thirty percent to 50% of patients require partial or complete
parenteral nutrition. Some patients can be treated with intermittent
enteral supplementation, whereas others can maintain themselves on
selective oral diets. Prokinetic drugs are generally used although
studies have not shown definitive evidence of their efficacy. Isolated
gastroparesis can follow episodes of viral gastroenteritis and spontane-
ously resolves, usually in 6-24 mo. Erythromycin, a motilin receptor
agonist, and cisapride, a serotonin 5-HT4 receptor agonist, can enhance
 Chapter 332  ◆  Motility Disorders and Hirschsprung Disease  1807
gastric emptying and proximal small bowel motility and may be useful
in this select group of patients. Metoclopramide, a prokinetic and
antinausea agent, is effective in gastroparesis, although side effects,
such as tardive dyskinesia, limit its use. Domperidone, an antidopami-
nergic agent, is a prokinetic agent available though the government in
special circumstances. Pain management is difficult and requires a
multidisciplinary approach.
Symptomatic small bowel bacterial overgrowth is usually treated
with rotated non-absorbable oral antibiotics and/or probiotics. Bacte-
rial overgrowth can be associated with steatorrhea and malabsorption.
Octreotide, a long-acting somatostatin analog, has been used in low
doses to treat small bowel bacterial overgrowth. Patients with acid
peptic symptoms are generally treated with acid suppression. Many
benefit from a gastrostomy and some benefit from decompressive
enterostomies. Colectomy with ileorectal anastomosis is beneficial if
the large bowel is the primary site of the motility abnormality. Bowel
transplantation may benefit selected patients.
Bibliography is available at Expert Consult.
332.2  Mitochondrial Neurogastrointestinal
Encephalomyopathy
Kristin N. Fiorino and Chris A. Liacouras
Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is
a multisystem autosomal recessive disease that initially presents with
severe gastrointestinal disturbances; the neurologic manifestations
usually occur later in the illness and may initially be subtle or
asymptomatic.
MNGIE is caused by a mutation in the nuclear DNA TYMP gene
encoding thymidine phosphorylase that results in abnormalities in
intergenomic communication with resulting instability of mitochon-
drial DNA. There are at least 50 individual mutations with a poor
genotype–phenotype correlation and varying manifestations within
each family. Consanguinity is present in 30% of families.
MNGIE affects both males and females and is usually diagnosed in
the 2nd and 3rd decade (average age: 18 yr; range: 5 mo-35 yr). Onset
is usually around age 12 yr, but there is often a 5-10 yr delay in the
diagnosis.
MNGIE initially presents with gastrointestinal symptoms. Severe
intestinal dysmotility and gastroparesis is associated with early satiety,
postprandial emesis, episodic pseudoobstruction, diarrhea, constipa-
tion and abdominal pain and cramping, which leads to significant
cachexia. Because of the age of onset, emesis, early satiety, and cachexia
patients are often misdiagnosed with an eating disorder.
Most often following the onset of gastrointestinal manifestations,
ptosis, progressive external ophthalmoplegia, hearing loss and periph-
eral neuropathy may develop. The neuropathy is either demyelinating
or a mixed axonal demyelinating type and manifests as weakness,
decreased or absent deep tendon reflexes, and paresthesias. Leukoen-
cephalopathy is initially asymptomatic and noted on MRI as patchy
lesions predominantly in the cortex but also in the basal ganglia and
brainstem. Eventually the central nervous system lesions become
diffuse and confluent. A small number of patients develop cognitive
impairment or dementia.
The diagnosis is suggested by the constellation of gastrointestinal
and neurologic symptoms, lactic acidosis, ragged red fibers, and cyto-
chrome C oxidase deficient fibers seen in most patients on muscle
biopsy.
Treatment is focused on providing sufficient nutritional support and
avoidance of infectious complications and of nutritional deficiencies.
Stem cell transplantation has been successful in a small number of
patients.
Overall the prognosis is poor with few surviving into the 4th or 5th
decade.
Bibliography is available at Expert Consult.
Downloaded from ClinicalKey.com at Universitas Kristen Duta Wacana January 20, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
332.3  Encopresis and Functional
Constipation
Kristin N. Fiorino and Chris A. Liacouras
Constipation is defined as a delay or difficulty in defecation present for
2 wk or longer and significant enough to cause distress to the patient.
Another approach to the definition is the Rome Criteria, outlined in
Table 332-2. Functional constipation, also known as idiopathic consti-
pation or fecal withholding, can usually be differentiated from consti-
pation secondary to organic causes on the basis of a history and physical
examination. Unlike anorectal malformations and Hirschsprung
disease, functional constipation typically starts after the neonatal
period. Usually, there is an intentional or subconscious withholding of
stool. An acute episode usually precedes the chronic course. The acute
episode may be a dietary change from human milk to cow’s milk, sec-
ondary to the change in the protein and carbohydrate ratio or an allergy
to cow’s milk. The stool becomes firm, smaller, and difficult to pass,
resulting in anal irritation and often an anal fissure. In toddlers, coer-
cive or inappropriately early toilet training is a factor that can initiate a
pattern of stool retention. In older children, retentive constipation can
develop after entering a situation that makes stooling inconvenient such
as school. Because the passage of bowel movements is painful, volun-
tary withholding of feces to avoid the painful stimulus develops.
CLINICAL MANIFESTATIONS
When children have the urge to defecate, typical behaviors include
contracting the gluteal muscles by stiffening the legs while lying down,
holding onto furniture while standing, or squatting quietly in corners,
waiting for the call to stool to pass. The urge to defecate passes as the
rectum accommodates to its contents. A vicious cycle of retention
develops, as increasingly larger volumes of stool need to be expelled.
Caregivers may misinterpret these activities as straining, but it is with-
holding behavior. There is often a history of blood in the stool noted
with the passage of a large bowel movement. Findings suggestive of
Table 332-2 Chronic Constipation: Rome III Criteria
INFANTS AND TODDLERS
Must include 1 mo of at least 2 of the following in infants up to 4 yr
of age:
• ≤2 Defecations per week
• ≥1 Episode of incontinence after the acquisition of toilet training
skills
• History of excessive stool retention
• History of painful or hard bowel movements
• Presence of a large fecal mass in the rectum
• History of a large-diameter stool that might obstruct the
toilet
Accompanying symptoms may include irritability, decreased
appetite, and/or early satiety. The accompanying symptoms
disappear immediately following passage of a large stool.
CHILDREN WITH A DEVELOPMENTAL AGE OF 4-18 YR
Must include 2 or more of the following in a child with a
developmental age of at least 4 yr with insufficient criteria for
diagnosis of irritable bowel syndrome*:
• ≤2 Defecations per week
• ≥1 Episode of fecal incontinence per week
• History of retentive posturing or excessive volitional stool
retention
• History of painful or hard bowel movements
• Presence of a large fecal mass in the rectum
• History of a large-diameter stool that might obstruct the
toilet
*Criteria fulfilled at least once per week for at least 2 mo before diagnosis.
From Hyman P, Milla P. Benninga M, et al: Childhood functional
gastrointestinal disorders: neonate/toddler, Gastroenterology 130:1519–1526,
2006; and Rasquin A, DiLorenzo C, Forbes D, et al: Childhood functional
gastrointestinal disorders: child/adolescent, Gastroenterology 130:1527–1537,
2006.
 Chapter 332  ◆  Motility Disorders and Hirschsprung Disease  1807.e1

Bibliography Iyer K, Kaufman S, Sudan D, et al: Long-term results of intestinal transplantation

Chumpitazi B, Nurko S: Pediatric gastrointestinal motility disorders: challenges
and a clinical update, Nat Rev Gastroenterol Hepatol 4(2):140–148, 2008.
Cucchiara S, Borrelli O, Salvia G, et al: A normal gastrointestinal motility excludes
chronic intestinal pseudo-obstruction in children, Dig Dis Sci 45:258–264, 2000.
Di Nardo G, Blandizzi C, Volta U, et al: Review article: molecular, pathological and
therapeutic features of human enteric neuropathies, Aliment Pharmacol Ther
28:25–42, 2008.
Gabbard S, Lacy B: Chronic intestinal pseudo-obstruction, Nutr Clin Pract
28(3):307–316, 2013.
Haftel LT, Lev D, Barash V, et al: Familial mitochondrial intestinal pseudo-
obstruction and neurogenic bladder, J Child Neurol 15:386–389, 2000.
for pseudo-obstruction in children, J Pediatr Surg 36:174–177, 2001.
Lapointe SP, Rivet C, Goulet O, et al: Urological manifestations associated with
chronic intestinal pseudo-obstructions in children, J Urol 168:1768–1770, 2002.
Mousa H, Hyman PE, Cocjin J, et al: Long-term outcome of congenital intestinal
pseudo-obstruction, Dig Dis Sci 47:2298–2305, 2002.
Venkatasubramani N, Sood M: Motility disorders of the gastrointestinal tract,
Indian J Pediatr 73:927–930, 2006.
Walker WA, Goulet O, Kleinman R, et al, editors: Pediatric gastrointestinal disease,
ed 4, Hamilton, Ontario, 2004, BC Decker.

Downloaded from ClinicalKey.com at Universitas Kristen Duta Wacana January 20, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
1807.e2  Chapter 332  ◆  Motility Disorders and Hirschsprung Disease

Bibliography Garone C, Tadesse S, Hirano M: Clinical and genetic spectrum of mitochondrial

Bariş Z, Eminoğlu T, Dalgiç B, et al: Mitochondrial neurogastrointestinal neurogastrointestinal encephalomyopathy, Brain 134:3326–3332, 2011.
encephalomyopathy (MNGIE): case report with a new mutation, Eur J Pediatr
169:1375–1378, 2010.

Downloaded from ClinicalKey.com at Universitas Kristen Duta Wacana January 20, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
1808  Part XVIII  ◆  The Digestive System

underlying pathology include failure to thrive, weight loss, abdominal

pain, vomiting, or persistent anal fissure or fistula.
In functional constipation, daytime encopresis is common. Encop-
resis is defined as voluntary or involuntary passage of feces into inap-
propriate places at least once a month for 3 consecutive months once
a chronologic or developmental age of 4 yr has been reached. Encop-
resis is not diagnosed when the behavior is exclusively the result of the
direct effects of a substance (e.g., laxatives) or a general medical condi-
tion (except through a mechanism involving constipation). Subtypes
include retentive encopresis (with constipation and overflow inconti-
nence) representing 65-95% of cases, and nonretentive encopresis
(without constipation and overflow incontinence). Nonretentive fecal
incontinence is defined as no evidence of fecal retention (impaction),
≥1 episodes per week in the previous 2 mo in a child at a developmen-
tal age >4 yr, defecation in places inappropriate to the social context
and no evidence of anatomic, inflammatory, metabolic, endocrine, or
neoplastic process that could explain the symptoms. Encopresis can
persist from infancy onward (primary) or can appear after successful
toilet training (secondary).

DIAGNOSIS
The physical examination often demonstrates a large volume of stool
palpated in the suprapubic area; rectal examination demonstrates a
dilated rectal vault filled with guaiac-negative stool. Children with
encopresis often present with reports of underwear soiling, and many
parents initially presume that diarrhea, rather than constipation, is the
cause. In retentive encopresis, associated complaints of difficulty with
defecation, abdominal or rectal pain, impaired appetite with poor
growth, and urinary (day and/or night) incontinence are common.
Children often have large bowel movements that obstruct the toilet.
There may also be retentive posturing or recurrent urinary tract infec-
tions. Nonretentive encopresis is more likely to occur as a solitary
symptom and have associated primary underlying psychological etiol-
ogy. Children with encopresis can present with poor school perfor-
mance and attendance that is triggered by the scorn and derision from
schoolmates because of the child’s offensive odor.
The presence of a hair tuft over the spine or spinal dimple, or failure
to elicit a cremasteric reflex or anal wink suggests spinal pathology. A
tethered cord is suggested by decreased or absent lower leg reflexes.
Spinal cord lesions can occur with overlying skin anomalies. Urinary
tract symptoms include recurrent urinary tract infection and enuresis.
Children with no evidence of abnormalities on physical examination
rarely require radiologic evaluation.
In refractory patients (intractable constipation), specialized testing
should be considered to rule out conditions such as hypothyroidism,
hypocalcemia, lead toxicity, celiac disease, and allergy testing. Colonic
transit studies using radio-opaque markers or scintigraphy techniques
may be useful. Selected children can benefit from MRI of the spine to
identify an intraspinal process, motility studies to identify underlying
myopathic or neuropathic bowel abnormalities, or a contrast enema to
identify structural abnormalities. In patients with severe functional
constipation, water-soluble contrast enema reveals the presence of a
megarectosigmoid (Fig. 332-1). Anorectal motility studies can demon-
strate a pattern of paradoxical contraction of the external anal sphinc-
ter during defecation, which can be treated by behavior modification
and biofeedback. Colonic motility can guide therapy in refractory
cases, demonstrating segmental problems that might require surgical
intervention.
Complications of retentive encopresis include day and night urinary
incontinence, urinary retention, urinary tract infection, megacystis,
and rarely toxic megacolon.
TREATMENT
Therapy for functional constipation and encopresis includes patient
education, relief of impaction, and softening of the stool. Caregivers
must understand that soiling associated with overflow incontinence is
Figure 332-1 Barium enema in a 14 yr old boy with severe constipa-
tion. The enormous dilation of the rectum and distal colon is typical of
acquired functional megacolon.
associated with loss of normal sensation and not a willful act. There
needs to be a focus on adherence with regular postprandial toilet sitting
and adoption of a balanced diet. In addition, caregivers should be
instructed not to respond to soiling with retaliatory or punitive mea-
sures, because children are likely to become angry, ashamed, and resis-
tant to intervention. From the outset, parents should be actively
encouraged to reward the child for adherence to a healthy bowel
regimen and to avoid power struggles.
If an impaction is present on the initial physical examination, an
enema is usually required to clear the impaction while stool softeners
are started as maintenance medications. Typical regimens include the
use of polyethylene glycol preparations, lactulose, or mineral oil (Tables
332-3 and 332-4). Prolonged use of stimulants such as senna or bisaco-
dyl should be avoided.
Compliance can wane, and failure of this standard treatment
approach sometimes requires more intensive intervention. In cases
where behavioral or psychiatric problems are evident, involvement of
a psychologist or behavioral management (e.g., behavior programs
and/or biofeedback). Maintenance therapy is generally continued until
a regular bowel pattern has been established and the association of pain
with the passage of stool is abolished.
For children with chronic diarrhea and/or irritable bowel syndrome
where stress and anxiety play a major role, stress reduction and learn-
ing effective coping strategies can play an important role in responding
to the encopresis. Relaxation training, stress inoculation, assertiveness
training, and/or general stress management procedures can be helpful.
Children with spinal problems can be successfully managed with low
volumes of fluid through a cecostomy or sigmoid tube.
Bibliography is available at Expert Consult.

Downloaded from ClinicalKey.com at Universitas Kristen Duta Wacana January 20, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
 Chapter 332  ◆  Motility Disorders and Hirschsprung Disease  1809

Table 332-3 Suggested Medications and Dosages for Disimpaction

MEDICATION AGE DOSAGE
RAPID RECTAL DISIMPACTION
Glycerin suppositories Infants and toddlers
Phosphate enema <1 yr 60 mL
>1 yr 6 mL/kg bodyweight, up to 135 mL twice
Milk of molasses enema Older children (1 : 1 milk : molasses) 200-600 mL
SLOW ORAL DISIMPACTION IN OLDER CHILDREN
Over 2-3 Days
Polyethylene glycol with electrolytes 25 mL/kg bodyweight/hr, up to 1000 mL/hr
until clear fluid comes from the anus
Over 5-7 Days
Polyethylene without electrolytes 1.5 g/kg bodyweight/day for 3 days
Milk of magnesia 2 mL/kg bodyweight twice/day for 7 days
Mineral oil 3 mL/kg bodyweight twice/day for 7 days
Lactulose or sorbitol 2 mL/kg bodyweight twice/day for 7 days
From Loening-Baucke V: Functional constipation with encopresis. In Wyllie R, Hyams JS, Kay M, editors: Pediatric gastrointestinal and liver disease, ed 3, Philadelphia,
2006, WB Saunders, p 183.

Table 332-4 Suggested Medications and Dosages for Maintenance Therapy of Constipation
MEDICATION AGE DOSE
FOR LONG-TERM TREATMENT (YEARS)
Milk of magnesia >1 mo 1-3 mL/kg bodyweight/day, divided into 1-2 doses
Mineral oil >12 mo 1-3 mL/kg bodyweight/day, divided into 1-2 doses
Lactulose or sorbitol >1 mo 1-3 mL/kg bodyweight/day, divided into 1-2 doses
Polyethylene glycol 3350 (MiraLAX) >1 mo 0.7 g/kg bodyweight/day, divided into 1-2 doses
FOR SHORT-TERM TREATMENT (MONTHS)
Senna (Senokot) syrup, tablets 1-5 yr 5 mL (1 tablet) with breakfast, max 15 mL daily
5-15 yr 2 tablets with breakfast, maximum 3 tablets daily
Glycerin enemas >10 yr 20-30 mL/day ( 12 glycerin and 12 normal saline)
Bisacodyl suppositories >10 yr 10 mg daily
From Loening-Baucke V: Functional constipation with encopresis. In Wyllie R, Hyams JS, Kay M, editors: Pediatric gastrointestinal and liver disease, ed 3, Philadelphia,
2006, WB Saunders, p. 185.

332.4  Congenital Aganglionic Megacolon
(Hirschsprung Disease)
Kristin N. Fiorino and Chris A. Liacouras
Hirschsprung disease, or congenital aganglionic megacolon, is a devel-
opmental disorder (neurocristopathy) of the enteric nervous system,
characterized by the absence of ganglion cells in the submucosal and
myenteric plexus. It is the most common cause of lower intestinal
obstruction in neonates, with an overall incidence of 1 in 5,000 live
births. The male : female ratio for Hirschsprung disease is 4 : 1 for short-
segment disease, and approximately 2 : 1 with total colonic agangliono-
sis. Prematurity is uncommon.
There is an increased familial incidence in long-segment disease.
Hirschsprung disease may be associated with other congenital defects,
including trisomy 21, Joubert syndrome, Goldberg-Shprintzen syn-
drome, Smith-Lemli-Opitz syndrome, Shah-Waardenburg syndrome,
cartilage-hair hypoplasia, multiple endocrine neoplasm 2 syndrome,
neurofibromatosis, neuroblastoma, congenital hypoventilation
(Ondine’s curse), and urogenital or cardiovascular abnormalities.
Hirschsprung disease has been seen in association with microcephaly,
mental retardation, abnormal facies, autism, cleft palate, hydrocepha-
lus, and micrognathia.
PATHOLOGY
Hirschsprung disease is the result of an absence of ganglion cells in the
bowel wall, extending proximally and continuously from the anus for
a variable distance. The absence of neural innervation is a consequence
of an arrest of neuroblast migration from the proximal to distal bowel.
Without the myenteric and submucosal plexus, there is inadequate
relaxation of the bowel wall and bowel wall hypertonicity, which can
lead to intestinal obstruction.
Hirschsprung disease is usually sporadic, although dominant and
recessive patterns of inheritance have been demonstrated in family
groups. Genetic defects have been identified in multiple genes that
encode proteins of the RET signaling pathway (RET, GDNF, and NTN)
and involved in the endothelin (EDN) type B receptor pathway
(EDNRB, EDN3, and EVE-1). Syndromic forms of Hirschsprung
disease have been associated with the L1CAM, SOX10, and ZFHX1B
(formerly SIP1) genes.
The aganglionic segment is limited to the rectosigmoid in 80%
of patients. Approximately 10-15% of patients have long-segment
disease, defined as disease proximal to the sigmoid colon. Total bowel
aganglionosis is rare and accounts for approximately 5% of cases.
Observed histologically is an absence of Meissner’s and Auerbach’s
plexuses and hypertrophied nerve bundles with high concentrations
of acetylcholinesterase between the muscular layers and in the
submucosa.
CLINICAL MANIFESTATIONS
Hirschsprung disease is usually diagnosed in the neonatal period sec-
ondary to a distended abdomen, failure to pass meconium, and/or
bilious emesis or aspirates with feeding intolerance. In 99% of
healthy full-term infants, meconium is passed within 48 hr of birth.
Hirschsprung disease should be suspected in any full-term infant (the
disease is unusual in preterm infants) with delayed passage of stool.
Some neonates pass meconium normally but subsequently present
with a history of chronic constipation. Failure to thrive with hypopro-
teinemia from protein-losing enteropathy is a less common presenta-
tion because Hirschsprung disease is usually recognized early in the
course of the illness. Breastfed infants might not suffer disease as severe
as formula-fed infants.
Failure to pass stool leads to dilation of the proximal bowel and
abdominal distention. As the bowel dilates, intraluminal pressure

Downloaded from ClinicalKey.com at Universitas Kristen Duta Wacana January 20, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
1810  Part XVIII  ◆  The Digestive System

Table 332-5 Distinguishing Features of Hirschsprung Disease and Functional Constipation

VARIABLE FUNCTIONAL HIRSCHSPRUNG DISEASE
HISTORY
Onset of constipation After 2 yr of age At birth
Encopresis Common Very rare
Failure to thrive Uncommon Possible
Enterocolitis None Possible
Forced bowel training Usual None
EXAMINATION
Abdominal distention Uncommon Common
Poor weight gain Rare Common
Rectum Filled with stool Empty
Rectal examination Stool in rectum Explosive passage of stool
Malnutrition None Possible
INVESTIGATIONS
Anorectal manometry Relaxation of internal anal sphincter Failure of internal anal sphincter relaxation
Rectal biopsy Normal No ganglion cells, increased acetylcholinesterase staining
Barium enema Massive amounts of stool, no transition zone Transition zone, delayed evacuation (>24 hr)
From Imseis E, Gariepy C: Hirschsprung disease. In Walker WA, Goulet OJ, Kleinman RE et al, editors: Pediatric gastrointestinal disease, ed 4, Hamilton, Ontario,
2004, BC Decker, p. 1035.

increases, resulting in decreased blood flow and deterioration of the

mucosal barrier. Stasis allows proliferation of bacteria, which can lead
to enterocolitis (Clostridium difficile, Staphylococcus aureus, anaerobes,
coliforms) with associated diarrhea, abdominal tenderness, sepsis and
signs of bowel obstruction. Early recognition of Hirschsprung disease
before the onset of enterocolitis is essential in reducing morbidity and
mortality.
Hirschsprung disease in older patients must be distinguished from
other causes of abdominal distention and chronic constipation (Table
332-5 and Fig. 332-2). The history often reveals constipation starting
in infancy that has responded poorly to medical management. Fecal
incontinence, fecal urgency, and stool-withholding behaviors are
usually not present. The abdomen is tympanitic and distended, with a
large fecal mass palpable in the left lower abdomen. Rectal examination
demonstrates a normally placed anus that easily allows entry of the
finger but feels snug. The rectum is usually empty of feces, and when
the finger is removed, there may be an explosive discharge of foul-
smelling feces and gas. The stools, when passed, can consist of small
pellets, be ribbon-like, or have a fluid consistency, unlike the large
stools seen in patients with functional constipation. Intermittent
attacks of intestinal obstruction from retained feces may be associated
with pain and fever. Urinary retention with enlarged balder or hydro-
nephrosis can occur secondary to urinary compression.
In neonates, Hirschsprung disease must be differentiated from
meconium plug syndrome, meconium ileus, and intestinal atresia. In
older patients, the Currarino triad must be considered, which includes
anorectal malformations (ectopic anus, anal stenosis, imperforate
anus), sacral bone anomalies (hypoplasia, poor segmentation), and
presacral anomaly (anterior meningoceles, teratoma, cyst).

DIAGNOSIS
Rectal suction biopsy is the gold standard for diagnosing Hirschsprung
disease. The biopsy material should contain an adequate amount of
submucosa to evaluate for the presence of ganglion cells. To avoid
obtaining biopsies in the normal area of hypoganglionosis, which
ranges from 3-17 mm in length, the suction rectal biopsy should be
obtained no closer than 2 cm above the dentate line. The biopsy speci-
men should be stained for acetylcholinesterase to facilitate interpreta-
tion. Patients with aganglionosis demonstrate a large number of
hypertrophied nerve bundles that stain positively for acetylcholines-
terase with an absence of ganglion cells. Calretinin staining may
provide a diagnosis of Hirschsprung disease when acetylcholinesterase
staining may not be sufficient.
Anorectal manometry evaluates the internal anal sphincter while a
balloon is distended in the rectum. In healthy individuals, rectal
Figure 332-2 Lateral view of a barium enema in a 3 yr old girl with
Hirschsprung disease. The aganglionic distal segment is narrow, with
distended normal ganglionic bowel above it.
distention initiates relaxation of the internal anal sphincter in response
to rectal distention. In patients with Hirschsprung disease, the internal
anal sphincter fails to relax in response to rectal distention. Although
the sensitivity and specificity can vary widely, in experienced hands,
the test can be quite sensitive. The test, however, can be technically
difficult to perform in young infants. A normal response in the course
of manometric evaluation precludes a diagnosis of Hirschsprung
disease; an equivocal or paradoxical response requires a repeat motility
or rectal biopsy.

Downloaded from ClinicalKey.com at Universitas Kristen Duta Wacana January 20, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
 Chapter 332  ◆  Motility Disorders and Hirschsprung Disease  1811
An unprepared contrast enema is most likely to aid in the diagnosis
in children older than 1 mo of age because the proximal ganglionic
segment might not be significantly dilated in the 1st few wk of life.
Classic findings are based on the presence of an abrupt narrow transi-
tion zone between the normal dilated proximal colon and a smaller-
caliber obstructed distal aganglionic segment. In the absence of this
finding, it is imperative to compare the diameter of the rectum to that
of the sigmoid colon, because a rectal diameter that is the same as or
smaller than the sigmoid colon suggests Hirschsprung disease. Radio-
logic evaluation should be performed without preparation to prevent
transient dilation of the aganglionic segment. As many as 10% of new-
borns with Hirschsprung disease have a normal contrast study. Twenty-
four-hour delayed films are helpful in showing retained contrast (see
Fig. 332-2). If significant barium is still present in the colon, it increases
the suspicion of Hirschsprung disease even if a transition zone is not
identified. Barium enema examination is useful in determining the
extent of aganglionosis before surgery and in evaluating other diseases
that manifest as lower bowel obstruction in a neonate. Full-thickness
rectal biopsies can be performed at the time of surgery to confirm the
diagnosis and level of involvement.
TREATMENT
Once the diagnosis is established, the definitive treatment is operative
intervention. Previously, a temporary ostomy was placed and definitive
surgery was delayed until the child was older. Currently, many infants
undergo a primary pull-through procedure except if there is associated
enterocolitis or other complications, when a decompressing ostomy is
usually required.
There are 3 basic surgical options. The first successful surgical pro-
cedure, described by Swenson, was to excise the aganglionic segment
and anastomose the normal proximal bowel to the rectum 1-2 cm
above the dentate line. The operation is technically difficult and led to
the development of 2 other procedures. Duhamel described a proce-
dure to create a neorectum, bringing down normally innervated bowel
behind the aganglionic rectum. The neorectum created in this proce-
dure has an anterior aganglionic segment with normal sensation and
a posterior ganglionic segment with normal propulsion. The endorec-
tal pull-through procedure described by Soave involves stripping the
mucosa from the aganglionic rectum and bringing normally inner-
vated colon through the residual muscular cuff, thus bypassing the
abnormal bowel from within. Advances in techniques have led to suc-
cessful laparoscopic single-stage endorectal pull-through procedures,
which are the treatment of choice.
In ultrashort-segment Hirschsprung disease, also known as anal
achalasia, the aganglionic segment is limited to the internal sphincter.
The clinical symptoms are similar to those of children with functional
constipation. Ganglion cells are present on rectal suction biopsy, but
the anorectal manometry is abnormal, with failure of relaxation of the
internal anal sphincter in response to rectal distention. Current treat-
ment, although controversial, includes anal botulism injection to relax
the anal sphincter and anorectal myectomy if indicated.
Long-segment Hirschsprung disease involving the entire colon and,
at times, part of the small bowel presents a difficult problem. Anorectal
manometry and rectal suction biopsy demonstrate findings of
Hirschsprung disease, but radiologic studies are difficult to interpret
because a colonic transition zone cannot be identified. The extent of
aganglionosis can be determined accurately by biopsy at the time of
laparotomy. When the entire colon is aganglionic, often together with
a length of terminal ileum, ileal-anal anastomosis is the treatment of
choice, preserving part of the aganglionic colon to facilitate water
absorption, which helps the stools to become firm.
The prognosis of surgically treated Hirschsprung disease is gen­
erally satisfactory; the great majority of patients achieve fecal con­
tinence. Long-term postoperative problems include constipation,
recurrent enterocolitis, stricture, prolapse, perianal abscesses, and
fecal soiling. Some children require myectomy or a redo pull-through
procedure.
Bibliography is available at Expert Consult.
Downloaded from ClinicalKey.com at Universitas Kristen Duta Wacana January 20, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
332.5  Intestinal Neuronal Dysplasia
Kristin N. Fiorino and Chris A. Liacouras
Intestinal neuronal dysplasia (IND) describes different quantitative
(hypo- or hyperganglionosis) and qualitative (immature or hetero-
tropic ganglion cells) abnormalities of the myenteric and/or submuco-
sal plexus. The typical histology is that of hyperganglionosis and giant
ganglia. Type A occurs very rarely and is characterized by congenital
aplasia or hypoplasia of the sympathetic innervation. Patients present
early in the neonatal period with episodes of intestinal obstruction,
diarrhea, and bloody stools. Type B, which accounts for more than 95%
of cases, is characterized by malformation of the parasympathetic sub-
mucous and myenteric plexus with giant ganglia and thickened nerve
fibers, increased acetylcholinesterase staining, and isolated ganglion
cells in the lamina propria. IND type B mimics Hirschsprung disease,
and patients present with chronic constipation.
Clinical manifestations include abdominal distention, constipation,
and enterocolitis. Various lengths of bowel may be affected from seg-
mental to the entire intestinal tract. IND has been observed in an
isolated form and proximal to an aganglionic segment. Other intra-
and extraintestinal manifestations are present in patients with IND. It
has been reported in all age groups, most commonly in infancy, but is
also seen in adults who have had constipation not dating back to
childhood.
Associated diseases and conditions include Hirschsprung disease,
prematurity, small left colon syndrome, and meconium plug syndrome.
Studies have identified a deficiency in substance P in patients with
IND. No mutations in the coding regions of the RET, GDNF, EDNRB,
or EDN3 genes have been identified.
Management includes that for functional constipation and, if unsuc-
cessful, surgery is indicated.
Bibliography is available at Expert Consult.
332.6  Superior Mesenteric Artery
Syndrome (Wilkie Syndrome, Cast
Syndrome, Arteriomesenteric
Duodenal Compression Syndrome)
Andrew Chu and Chris A. Liacouras
Superior mesenteric artery syndrome results from compression of the
3rd duodenal segment by the artery against the aorta. Malnutrition or
catabolic states may cause mesenteric fat depletion, which collapses the
duodenum within a narrowed aortomesenteric angle. Other etiologies
include extraabdominal compression (e.g., body cast) and mesenteric
tension, as can occur from ileoanal pouch anastomosis.
Symptoms include intermittent epigastric pain, anorexia, nausea,
and vomiting. Risk factors include thin body habitus, prolonged bed
rest, abdominal surgery, and exaggerated lumbar lordosis. Onset can
be within weeks of a trigger, but some patients have chronic symptoms
that evade diagnosis. A classic example is an underweight adolescent
who begins vomiting 1-2 wk following scoliosis surgery. Recognition
may be delayed in the context of an eating disorder.
The diagnosis is established radiologically by demonstrating a duo-
denal cutoff just right of midline along with proximal duodenal dila-
tion, with or without gastric dilation. Although the upper gastrointestinal
series remains a mainstay, modalities including CT, MR angiography,
or ultrasound may be more appropriate if there is concern for other
etiologies like malignancy. Upper endoscopy should be considered to
rule out intraluminal pathology.
Treatment focuses on obstructive relief, nutritional rehabilitation,
and correction of associated fluid and electrolyte abnormalities. Lateral
or prone positioning can shift the duodenum away from obstructing
structures and allow resumption of oral intake. In such cases, proki-
netic agents (e.g., erythromycin) may be helpful. If repositioning is
 Chapter 332  ◆  Motility Disorders and Hirschsprung Disease  1811.e1

Bibliography Emmanuel AV, Kamm MA: Response to a behavioral treatment, biofeedback, in

Auth MKH, Vora R, Farrelly P, et al: Childhood constipation, BMJ 345:38–43,
2012.
Bekkali NLH, van den Berg MM, Dijkgraaf MGW, et al: Rectal fecal impaction
treatment in childhood constipation: enemas versus high doses oral PEG,
Pediatrics 124:e1108–e1115, 2009.
Boners ME, Tabbers MM, Benninga MA: Functional nonretentive fecal
incontinence in children, J Pediatr Gastroenterol Nutr 44:5–13, 2007.
Burgers R, Levin AD, Di Lorenzo C, et al: Functional defecation disorders in
children: comparing the Rome II with the Rome III criteria, J Pediatr
161:615–620, 2012.
Camilleri M, Kerstens R, Rykx A, et al: A placebo-controlled trial of prucalopride
for severe chronic constipation, N Engl J Med 358:2344–2354, 2008.
Candy D, Belsey J: Macrogol (polyethylene glycol) laxatives in children with
functional constipation and faecal impaction: a systematic review, Arch Dis
Child 94:156–160, 2009.
Carvalho RS, Michail SK, Ashai-Khan F, et al: An update in pediatric
gastroenterology and nutrition: a review of some recent advances, Curr Probl
Pediatr Adolesc Health Care 38:197–234, 2008.
constipated patients is associated with improved gut transit and autonomic
innervation, Gut 49:214–219, 2001.
Masi P, Miele E, Staiano A: Pediatric anorectal disorders, Gastroenterol Clin North
Am 37:709–730, 2008.
Pijpers M, Tabbers M, Benninga M, et al: Currently recommended treatments of
childhood constipation are not evidence based: a systematic literature review on
the effect of laxative treatment and dietary measures, Arch Dis Child 94:117–
131, 2009.
Reid H, Bahar RJ: Treatment of encopresis and chronic constipation in young
children: clinical results from interactive parent-child guidance, Clin Pediatr
(Phila) 45:157–164, 2006.
Rosen R, Buonomo C, Andrade R, et al: Incidence of spinal cord lesions in patients
with intractable constipation, J Pediatr 145:409–411, 2004.
Voskuijl WP, Reitsma JB, van Ginkel R, et al: Longitudinal follow-up of children
with functional nonretentive fecal incontinence, Clin Gastroenterol Hepatol
4:67–72, 2006.

Downloaded from ClinicalKey.com at Universitas Kristen Duta Wacana January 20, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
1811.e2  Chapter 332  ◆  Motility Disorders and Hirschsprung Disease
Bibliography
Amiel J, Sproat-Emison E, Garcia-Barcelo M, et al: Hirschsprung disease,
associated syndromes and genetics: a review, J Med Genet 45:1–14, 2008.
Arshad A, Powell C, Tighe MP: Hirschsprung’s disease, BMJ 345:47–49, 2012.
Bonnard A, Zeidan S, Degas V, et al: Outcomes of Hirschsprung’s disease
associated with Mowat-Wilson syndrome, J Pediatr Surg 44:587–591, 2009.
Dasgupta R, Langer J: Hirschsprung disease, Curr Probl Surg 41:942–988, 2004.
Dasgupta R, Langer J: Evaluation and management of persistent problems after
surgery for Hirschsprung disease in a child, J Pediatr Gastroenterol Nutr
46(1):13–19, 2008.
DeLorijn F, Reitsma JB, Voskuijl WP, et al: Diagnosis of Hirschsprung’s disease: a
prospective comparative accuracy study of common tests, J Pediatr 146:787–
792, 2005.
Hackam D, Reblock K, Barksdale E, et al: The influence of Down’s syndrome on
the management and outcome of children with Hirschsprung’s disease, J Pediatr
Surg 38:946–949, 2003.
Haricharan R, Georgeson K: Hirschsprung disease, Semin Pediatr Surg 17:266–275,
2008.
Keshtgar AS, Ward HC, Clayden GS, et al: Investigations for incontinence and
constipation after surgery for Hirschsprung’s disease in children, Pediatr Surg
Int 19:4–8, 2003.
Downloaded from ClinicalKey.com at Universitas Kristen Duta Wacana January 20, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
Langer JC: Hirschsprung disease, Curr Opin Pediatr 25:368–374, 2013.
Langer JC, Durrant AC, de la Torre L, et al: One-stage transanal Soave pull
through for Hirschsprung disease: a multicenter experience with 141 children,
Ann Surg 238:569–583, discussion 583–585, 2003.
Moore SW: Chromosomal and related mendelian syndromes associated with
Hirschsprung’s disease, Pediatr Surg Int 28:1045–1058, 2012.
Morris M, Soglio D, Quimet A, et al: A study of calretinin in Hirschsprung disease
pathology, particularly total colonic Hirschsprung disease, J Pediatr Surg
48(5):1037–1043, 2013.
Ozyurek H, Kayacik OE, Gunger O, et al: Rare association of Hirschsprung’s
disease and Joubert syndrome, Eur J Pediatr 167:475–477, 2008.
Pensabene L, Youssef NN, Griffiths JM, et al: Colonic manometry in children with
defecatory disorders. Role in diagnosis and management, Am J Gastroenterol
98:1052–1057, 2003.
Prato AP, Musso M, Ceccherini I, et al: Hirschsprung disease and congenital
anomalies of the kidney and urinary tract (CAKUT), Medicine (Baltimore)
88:83–90, 2009.
Walker WA, Goulet O, Kleinman R, et al, editors: Pediatric gastrointestinal disease,
ed 4, Hamilton, Ontario, 2004, BC Decker.
 Chapter 332  ◆  Motility Disorders and Hirschsprung Disease  1811.e3

Bibliography Montedonico S, Acevedo S, Fadda B: Clinical aspects of intestinal neuronal

Hutson J, McNamara J, Shin Y: Review article: slow transit constipation in dysplasia, J Pediatr Surg 37(12):1772–1774, 2002.
children, J Paediatr Child Health 37:426–430, 2001. Walker WA, Goulet O, Kleinman R, et al, editors: Pediatric gastrointestinal disease,
Kapur R: Neuropathology of paediatric chronic intestinal pseudo-obstruction and ed 4, Hamilton, Ontario, 2004, BC Decker.
related animal models, J Pathol 194:277–288, 2001.

Downloaded from ClinicalKey.com at Universitas Kristen Duta Wacana January 20, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
unsuccessful, patients require nasojejunal enteral nutrition past the
obstruction or parenteral nutrition if this is not tolerated. Patients with
refractory courses may require surgery to bypass the obstruction.

Bibliography is available at Expert Consult.

Downloaded from ClinicalKey.com at Universitas Kristen Duta Wacana January 20, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
 Chapter 332  ◆  Motility Disorders and Hirschsprung Disease  1812.e1

Bibliography
Merrett ND, Wilson RB, Cosman P, et al: Superior mesenteric artery syndrome:
diagnosis and treatment strategies, J Gastrointest Surg 13:287–292, 2009.

Downloaded from ClinicalKey.com at Universitas Kristen Duta Wacana January 20, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.