Hirschsprung Disease

Overview

Hirschsprung disease, also known as congenital aganglionic megacolon, is a birth defect characterized by the absence of nerve cells (ganglion cells) in portions of the large intestine (colon) and sometimes extending into the small intestine. These missing nerve cells are crucial for the normal rhythmic contractions (peristalsis) that move stool through the bowel. Without these nerve cells, the affected segment of bowel cannot relax properly, creating a functional obstruction that prevents the normal passage of stool. This leads to a buildup of stool above the affected area, causing the bowel to become enlarged (megacolon) and potentially leading to serious complications if not treated promptly.

The condition occurs during fetal development when nerve cells stop migrating down the intestine before reaching the end of the colon. The extent of the disease varies considerably: in about 80% of cases, only the last portion of the colon (rectosigmoid) is affected, known as short-segment disease. However, the entire colon can be involved (total colonic aganglionosis), and rarely, the disease extends into the small intestine. Hirschsprung disease affects approximately 1 in 5,000 newborns, with boys being four times more likely to have the condition than girls. The disease is usually diagnosed in the newborn period when infants fail to pass meconium within the first 48 hours of life, though milder cases may not be diagnosed until later in childhood or even adulthood.

The importance of early diagnosis and treatment cannot be overstated, as untreated Hirschsprung disease can lead to life-threatening complications. The most serious acute complication is Hirschsprung-associated enterocolitis (HAEC), a condition where the bowel becomes inflamed and infected, potentially leading to sepsis and death. Other complications include severe constipation, abdominal distension, malnutrition, and failure to thrive. Fortunately, with modern surgical techniques, most children with Hirschsprung disease can be successfully treated and go on to lead normal lives, though they may require ongoing management for bowel function issues. The standard treatment involves surgical removal of the affected bowel segment and reconnecting the healthy bowel to the anus, allowing for more normal bowel movements.

Symptoms

Symptoms of Hirschsprung disease vary based on the age at diagnosis and the extent of bowel involvement. Most cases present in the newborn period, but some milder forms may not be recognized until later.

Newborn Symptoms (First 48 Hours)

Infant Symptoms (First Year)

• Chronic severe constipation
• Ribbon-like or liquid stools
• Explosive diarrhea after rectal exam
• Failure to gain weight appropriately
• Poor growth despite adequate intake
• Gas and bloating
• Visible intestinal movements (peristaltic waves)

Older Children Symptoms

• Chronic constipation since birth
• Abdominal distension
• Dependency on enemas or laxatives
• Lack of urge to have bowel movements
• Malnutrition and growth delay
• Anemia from poor nutrition
• Emotional distress from chronic symptoms

Enterocolitis Symptoms (Medical Emergency)

• Fever and lethargy
• Explosive, foul-smelling diarrhea
• Severe abdominal distension
• Vomiting
• Signs of dehydration
• Shock symptoms (pale, clammy skin)
• Rapid deterioration of condition

Associated Features by Segment Length

Short-Segment Disease

• May have delayed diagnosis
• Less severe symptoms initially
• Chronic constipation main feature
• May pass some stool

Long-Segment Disease

• Earlier, more severe presentation
• Complete obstruction more likely
• Higher risk of enterocolitis
• More nutritional complications

Total Colonic Aganglionosis

• Most severe symptoms
• Early complete obstruction
• May have small bowel involvement
• Complex surgical management needed

Physical Examination Findings

• Distended, tympanitic abdomen
• Palpable fecal masses
• Empty rectum on digital exam
• Explosive stool release after exam
• Tight anal sphincter
• Visible peristalsis

Complications Symptoms

• Signs of intestinal perforation
• Peritonitis (rigid abdomen, severe pain)
• Sepsis symptoms
• Severe dehydration
• Electrolyte imbalances
• Protein-losing enteropathy

Causes

Hirschsprung disease results from the failure of neural crest cells to complete their migration along the intestine during fetal development, leading to an absence of ganglion cells in affected bowel segments.

Developmental Abnormality

Neural Crest Cell Migration Failure

• Occurs between 5th and 12th week of gestation
• Neural crest cells migrate from esophagus to anus
• Migration stops prematurely in Hirschsprung disease
• Results in aganglionic (lacking nerve cells) segment
• Always involves rectum and extends proximally
• Length of affected segment varies

Genetic Factors

Known Genetic Mutations

• RET gene: Major susceptibility gene (50% of familial cases)
• EDNRB gene: Endothelin receptor type B
• EDN3 gene: Endothelin 3
• GDNF gene: Glial cell line-derived neurotrophic factor
• SOX10 gene: Associated with Waardenburg syndrome
• Multiple other minor susceptibility genes

Inheritance Patterns

• Most cases are sporadic (not inherited)
• Familial cases show complex inheritance
• 3-7% recurrence risk in siblings
• Higher risk if parent affected
• Male predominance suggests sex-linked factors
• Variable penetrance and expression

Associated Chromosomal Abnormalities

• Down syndrome: 10% of Hirschsprung patients
• Other chromosomal deletions
• Chromosomal translocations
• Complex genetic syndromes

Pathophysiology

Functional Consequences

• Absence of ganglion cells in myenteric plexus
• Lack of nitric oxide synthase neurons
• Unopposed cholinergic innervation
• Sustained contraction of affected segment
• Functional obstruction develops
• Proximal bowel dilates with retained stool

Cellular Abnormalities

• Hypertrophied nerve trunks
• Increased acetylcholinesterase activity
• Abnormal smooth muscle arrangement
• Altered intestinal pacemaker cells
• Disrupted neurotransmitter balance

Environmental Factors

• Maternal factors during pregnancy (under study)
• Possible viral infections in utero
• Maternal vitamin deficiencies
• Environmental toxins (theoretical)
• No proven preventable causes

Associated Syndromes

• Down syndrome (most common)
• Waardenburg-Shah syndrome
• Congenital central hypoventilation syndrome
• Mowat-Wilson syndrome
• Multiple endocrine neoplasia type 2
• Smith-Lemli-Opitz syndrome
• Cartilage-hair hypoplasia

Risk Factors

Several factors increase the likelihood of a child being born with Hirschsprung disease, though many cases occur without identifiable risk factors.

Genetic Risk Factors

• Family history: 7% risk if sibling affected
• Affected parent: Higher transmission from mother
• Male gender: 4:1 male-to-female ratio
• Genetic mutations: RET gene variants
• Consanguinity: Increased risk in related parents

Associated Conditions

Chromosomal Abnormalities

• Down syndrome (Trisomy 21) - 10% association
• Other chromosomal anomalies
• Genetic syndromes
• Multiple congenital anomalies

Other Birth Defects

• Congenital heart disease
• Urogenital abnormalities
• Gastrointestinal malformations
• Central nervous system defects
• Limb abnormalities

Familial Factors

• Higher risk in familial cases
• Long-segment disease more heritable
• Multiple affected family members
• Specific ethnic backgrounds (varied risk)
• Genetic counseling recommended

Maternal Factors

• Advanced maternal age (slight increase)
• Maternal illness during pregnancy
• Medication use (under investigation)
• Nutritional deficiencies (theoretical)
• No proven preventable maternal factors

Disease Extent Risk Factors

Short-Segment Disease

• More common in males
• Sporadic occurrence usual
• Lower familial recurrence
• Better prognosis

Long-Segment Disease

• Equal gender distribution
• Higher genetic component
• Increased sibling risk
• More associated anomalies

Population Risk Factors

• Affects all ethnic groups
• Slightly higher in Asian populations
• No seasonal variation
• No geographic clustering
• Urban vs rural no difference

Diagnosis

Diagnosis of Hirschsprung disease requires a combination of clinical suspicion, imaging studies, and definitive histological confirmation through biopsy showing absence of ganglion cells.

Clinical Evaluation

History Taking

• Delayed passage of meconium (>48 hours)
• Chronic constipation from birth
• Abdominal distension pattern
• Feeding history and weight gain
• Family history of Hirschsprung disease
• Response to rectal stimulation

Physical Examination

• Abdominal inspection and palpation
• Assessment of distension
• Digital rectal examination
• Empty rectum with tight sphincter
• Explosive stool on withdrawal
• General nutritional status

Imaging Studies

Contrast Enema

• Initial imaging study of choice
• Shows transition zone in 80% of cases
• Narrow aganglionic segment
• Dilated proximal bowel
• Delayed films show retention
• May be normal in newborns

Plain Abdominal X-rays

• Dilated bowel loops
• Air-fluid levels
• Absence of rectal gas
• Monitor for complications
• Not diagnostic alone

Definitive Diagnostic Tests

Rectal Suction Biopsy

• Gold standard for diagnosis
• Can be done bedside
• Samples taken 2-3 cm above dentate line
• Minimal risk and discomfort
• Adequate tissue in 90% of cases
• Requires experienced pathologist

Full-Thickness Biopsy

• If suction biopsy inconclusive
• Requires general anesthesia
• Provides definitive diagnosis
• Shows all bowel wall layers
• Can assess extent of disease

Histological Findings

• Absence of ganglion cells
• Hypertrophied nerve trunks
• Increased acetylcholinesterase staining
• Abnormal calretinin immunostaining
• Special stains may be needed
• Frozen section during surgery

Anorectal Manometry

• Measures internal sphincter relaxation
• Absent relaxation in Hirschsprung
• Useful screening in older children
• High negative predictive value
• Technical challenges in infants
• Not definitive diagnosis

Differential Diagnosis

• Meconium plug syndrome: Resolves with enema
• Small left colon syndrome: In diabetic mothers
• Intestinal neuronal dysplasia: Different histology
• Chronic constipation: Functional, not from birth
• Hypothyroidism: Check thyroid function
• Cystic fibrosis: Meconium ileus

Prenatal Diagnosis

• Not reliably detected prenatally
• Dilated bowel loops sometimes seen
• Polyhydramnios possible
• Genetic testing if family history
• Associated anomalies may be detected

Treatment Options

Treatment of Hirschsprung disease is surgical, involving removal of the aganglionic bowel segment and reconnecting healthy bowel to preserve normal function.

Initial Medical Management

Preoperative Stabilization

• Nasogastric decompression
• Intravenous fluid resuscitation
• Correction of electrolyte imbalances
• Antibiotics if enterocolitis present
• Nutritional support
• Rectal irrigations to decompress

Bowel Preparation

• Serial rectal irrigations
• Saline washouts
• Antibiotic bowel preparation
• Clear liquid diet if tolerated
• Monitor for enterocolitis

Surgical Treatment

Single-Stage Pull-Through Procedures

• Transanal approach: No abdominal incision
• Laparoscopic-assisted: Minimal invasive
• Open procedure: Traditional approach
• Performed in stable newborns
• Removes aganglionic bowel
• Anastomosis of normal bowel to anus

Multi-Stage Procedures

• Stage 1: Diverting colostomy
• Stage 2: Pull-through procedure
• Stage 3: Colostomy closure
• For sick infants or total colonic disease
• Allows bowel decompression
• Time for growth and stabilization

Surgical Techniques

Swenson Procedure

• Original pull-through technique
• Full-thickness rectosigmoidectomy
• End-to-end anastomosis
• Preserves internal sphincter

Duhamel Procedure

• Retrorectal pull-through
• Side-to-side anastomosis
• Creates rectal pouch
• Less sphincter manipulation

Soave Procedure

• Endorectal pull-through
• Mucosal stripping technique
• Preserves rectal muscular cuff
• Can be done transanally

Postoperative Care

• Pain management
• Gradual diet advancement
• Monitor bowel function
• Anal dilations if needed
• Watch for complications
• Stool softeners initially

Long-Term Management

Bowel Management Program

• Toilet training strategies
• Regular bowel habits
• Dietary modifications
• Fiber supplementation
• Adequate hydration
• Laxatives if needed

Follow-up Care

• Regular surgical follow-up
• Monitor growth and development
• Assess continence
• Manage constipation
• Screen for enterocolitis
• Psychological support

Treatment of Complications

Enterocolitis Management

• Hospital admission
• IV antibiotics (metronidazole)
• Rectal irrigations
• Fluid resuscitation
• Consider probiotics
• Prevention strategies

Managing Incontinence

• Bowel management programs
• Biofeedback therapy
• Enema regimens
• Dietary modifications
• Medication adjustments
• Surgical revision if severe

Special Considerations

• Total colonic aganglionosis: Complex management
• Associated syndromes: Multidisciplinary care
• Failed pull-through: Redo surgery options
• Transition to adult care: Ongoing needs

Prevention

As Hirschsprung disease is a congenital condition occurring during fetal development, primary prevention is not currently possible. Focus is on genetic counseling and preventing complications.

Genetic Counseling

For Affected Families

• Risk assessment for future pregnancies
• Sibling risk approximately 3-7%
• Higher risk with long-segment disease
• Genetic testing for known mutations
• Prenatal counseling options
• Family planning discussions

Genetic Testing Considerations

• RET gene mutation screening
• Testing in familial cases
• Associated syndrome evaluation
• Implications for family members
• Cost-benefit analysis

Preventing Complications

Enterocolitis Prevention

• Early diagnosis and treatment
• Regular bowel evacuations
• Prompt treatment of constipation
• Recognition of warning signs
• Prophylactic antibiotics (selected cases)
• Probiotics (under investigation)

Post-Surgical Complications

• Meticulous surgical technique
• Appropriate patient selection
• Proper bowel preparation
• Early mobilization
• Infection prevention protocols
• Regular follow-up care

Optimizing Outcomes

• Early recognition and referral
• Experienced surgical centers
• Multidisciplinary team approach
• Family education and support
• Long-term management plans
• Transition care planning

Quality of Life Measures

• Bowel management programs
• Dietary optimization
• Physical activity encouragement
• Psychological support
• Peer support groups
• School accommodations

Research and Future Directions

• Gene therapy investigations
• Stem cell research
• Improved diagnostic methods
• Novel surgical techniques
• Better understanding of genetics
• Prevention strategies development

When to See a Doctor

Early recognition of Hirschsprung disease is crucial. Parents should seek immediate medical attention for concerning symptoms in newborns and children.

Newborn Warning Signs

• No meconium passage within 48 hours
• Vomiting, especially green (bile)
• Abdominal distension
• Refusing to feed
• Failure to pass gas
• Signs of pain or distress

Emergency Symptoms

• Fever with abdominal distension
• Explosive diarrhea with fever
• Lethargy or listlessness
• Signs of dehydration
• Bloody diarrhea
• Severe abdominal pain
• Shock symptoms

Chronic Symptoms Requiring Evaluation

• Chronic constipation from birth
• Failure to thrive
• Dependency on enemas or suppositories
• Persistent abdominal distension
• Ribbon-like stools
• Poor weight gain despite good appetite

Post-Surgical Concerns

• Fever after surgery
• Increasing abdominal distension
• Persistent vomiting
• No bowel movements
• Signs of wound infection
• Severe diarrhea

Long-Term Follow-Up Needs

• Regular surgical check-ups
• Growth monitoring
• Bowel function assessment
• Continence issues
• Nutritional evaluation
• Developmental screening

When to Contact Surgeon

• Signs of enterocolitis
• Bowel obstruction symptoms
• Failure of bowel management
• Need for anal dilations
• Questions about activities
• Concerns about outcomes

Related Conditions

Frequently Asked Questions