Pediatrics (System-Integrated)

Hirschsprung disease: diagnosis and management

Clinical Overview and When to Suspect Hirschsprung Disease

— Aganglionic segment is always continuous and begins at the internal anal sphincter, extending proximally a variable distance

— Rectosigmoid ("short-segment") disease in ~80%, long-segment in ~15%, total colonic aganglionosis in ~5%

— Newborn who fails to pass meconium within 48 hours of life (passes within 24 hrs in >90% of healthy term infants, 99% by 48 hrs)

— Neonatal bilious emesis, abdominal distention, and refusal of feeds

— Older infant/child with chronic severe constipation since birth, failure to thrive, ribbon-like stools, and an empty rectal vault on exam

— Enterocolitis presentation: explosive foul-smelling diarrhea, fever, distention, sepsis — life-threatening, can be the initial presentation

— Trisomy 21 (Down syndrome) — present in ~10% of Hirschsprung cases; lowers threshold to investigate

— MEN2A/RET proto-oncogene mutations, Waardenburg syndrome, neurofibromatosis, congenital central hypoventilation (Haddad syndrome)

Board pearl: Any term newborn who has not passed meconium by 48 hours gets a Hirschsprung workup, even if otherwise well-appearing — the differential also includes meconium ileus (CF) and anorectal malformation, but Hirschsprung is the most common cause.

Definition: Congenital aganglionosis of the distal bowel — absence of ganglion cells in the Meissner (submucosal) and Auerbach (myenteric) plexuses due to failed craniocaudal migration of neural crest cells between weeks 5–12 of gestation

Epidemiology: ~1 in 5,000 live births; male predominance 4:1 for short-segment disease (ratio narrows in long-segment)

When to suspect:

Key associations:

Why it matters on Step 3: Although typically diagnosed by pediatric surgery in infancy, adolescents and young adults with ultra-short-segment disease may still present to primary care with lifelong constipation refractory to laxatives — recognition prevents years of mismanagement

Presentation Patterns and Key History

— Delayed meconium passage >48 hours — single most sensitive historical clue

— Bilious vomiting, progressive abdominal distention, poor feeding within first days of life

— Transient symptomatic relief after digital rectal exam or rectal stimulation (explosive expulsion of gas/stool — the "squirt sign")

— Chronic constipation dating from birth, not acquired later

— Failure to thrive, poor weight gain, abdominal distention with visible bowel loops

— Stools described as ribbon-like, pellet-like, or explosive after manual disimpaction

— No soiling/encopresis (contrast with functional constipation)

— Lifelong laxative or enema dependence, recurrent fecal impaction, growth delay

— Fever, explosive foul/bloody diarrhea, abdominal distention, lethargy, shock

— Mortality up to 30% if missed; can occur pre- or post-operatively

— Timing of first meconium passage (ask parents directly)

— Stooling pattern since birth — true Hirschsprung never has a "normal infancy" period

— Family history of Hirschsprung, Down syndrome, MEN2, congenital deafness, or cardiac defects

— Prenatal ultrasound findings — dilated bowel loops, polyhydramnios

— Onset <1 month of age, failure to thrive, no stool withholding behavior, no encopresis, empty rectum on DRE, tight anal canal

Key distinction: Functional constipation typically begins after toilet training or dietary transition (toddler age), with stool withholding, encopresis, and a rectum full of stool on DRE. Hirschsprung begins at birth, no encopresis, empty rectum with explosive release on withdrawal of the examining finger.

Neonatal presentation (>90% of cases diagnosed here):

Infant/toddler presentation:

Older child/adolescent presentation (short or ultra-short segment):

Hirschsprung-associated enterocolitis (HAEC) — can be presenting feature:

Key history points to nail down:

Red flags that push toward Hirschsprung over functional constipation:

Physical Exam Findings

— Neonate may appear ill, lethargic, dehydrated, or septic if enterocolitis present

— Older infant: failure to thrive, low weight-for-age, abdominal protuberance disproportionate to thin extremities

— Marked abdominal distention, often tympanitic

— Visible bowel loops in thin-walled infant abdomen

— Palpable stool in left lower quadrant possible but rectum itself is empty

— Tenderness, guarding, or peritoneal signs suggest enterocolitis, perforation, or toxic megacolon — surgical emergency

— Tight, narrow anal canal with normal-appearing perineum (rules out imperforate anus)

— Empty rectal vault (no stool palpable)

— "Squirt sign" / "blast sign": explosive release of gas and liquid stool upon withdrawal of the examining finger — highly suggestive

— Tachycardia, hypotension, fever, or capillary refill >3 sec → suspect HAEC with septic shock

— Hypothermia in neonates is an ominous sign of sepsis

— Down syndrome features: upslanting palpebral fissures, single palmar crease, hypotonia, flat facies, AV canal murmur

— Waardenburg: white forelock, heterochromia iridum, sensorineural deafness, dystopia canthorum

— Neurocristopathy spectrum: café-au-lait macules (NF1), thyroid mass (MEN2)

— Perianal soiling/encopresis (argues against functional constipation)

— Sacral dimple, hairy patch, or absent anal wink → think tethered cord/spinal dysraphism as alternative diagnosis

Step 3 management: A neonate with abdominal distention, fever, and bloody diarrhea on the floor — do not simply give an enema. Obtain abdominal X-ray, blood/stool cultures, broad-spectrum antibiotics (ampicillin/gentamicin/metronidazole), IV fluids, NPO, NG decompression, and urgent pediatric surgery consult for suspected HAEC.

General appearance:

Abdominal exam:

Digital rectal exam — the highest-yield maneuver:

Vital signs / hemodynamic assessment:

Associated syndromic findings to look for:

What you will NOT see:

Diagnostic Workup — Initial Labs and Imaging

— CBC with differential — leukocytosis or leukopenia with bandemia in enterocolitis

— BMP — hyponatremia, hypokalemia, metabolic acidosis from third-spacing and diarrhea

— Lactate, blood cultures, CRP if septic

— Coagulation studies preoperatively

— Type and screen

— Dilated proximal bowel loops with paucity of gas in the rectum/pelvis

— Air-fluid levels suggesting distal obstruction

— Free air → perforation, surgical emergency

— In HAEC: bowel wall thickening, pneumatosis intestinalis, "cutoff sign" at rectosigmoid

— Best initial diagnostic imaging study in stable patients

— Classic finding: "transition zone" — narrow aganglionic distal segment with dilated proximal ganglionic bowel

— Rectosigmoid ratio <1 (rectum smaller than sigmoid) — highly suggestive (normally rectum ≥ sigmoid in caliber)

— 24-hour delayed film: retained contrast in colon supports diagnosis

— Avoid bowel prep or DRE in the 24–48 hours before the study — can dilate the aganglionic segment and mask the transition zone

— Less reliable in neonates <1 month (transition zone may not have developed yet)

— Misses ultra-short-segment and total colonic aganglionosis (no visible transition; whole colon may look small — "microcolon")

— Absence of the rectoanal inhibitory reflex (RAIR) — internal sphincter fails to relax with rectal balloon distention

— High sensitivity; useful screening tool when biopsy logistics are difficult

Board pearl: The rectosigmoid ratio <1 on contrast enema is the radiographic signature of Hirschsprung. But remember: a normal contrast enema does NOT exclude the diagnosis — if clinical suspicion remains, proceed to rectal biopsy, which is the gold standard.

Initial labs (especially if ill-appearing or suspected HAEC):

Abdominal radiograph (first-line imaging):

Contrast enema (unprepped, water-soluble or low-osmolar contrast):

Limitations of contrast enema:

Anorectal manometry (useful in older children/adults):

Diagnostic Workup — Confirmatory Studies

— Suction rectal biopsy in infants <1 year: bedside procedure, no anesthesia, obtains submucosal tissue, low complication rate

— Full-thickness rectal biopsy in older children/adults: requires anesthesia, samples both submucosal and myenteric plexuses

— Biopsy must be taken at least 1–2 cm above the dentate line — the distal 1–2 cm is normally hypoganglionic and would yield a false positive

— Absence of ganglion cells in submucosal (Meissner) and myenteric (Auerbach) plexuses — defining feature

— Hypertrophied, hyperplastic nerve trunks in the submucosa (>40 μm diameter)

— Increased acetylcholinesterase (AChE) staining in the lamina propria and muscularis mucosae from proliferating cholinergic fibers

— Calretinin immunohistochemistry — absent in aganglionic segment; sensitive, easy to interpret, and increasingly preferred over AChE in many centers

— Consider RET proto-oncogene testing in familial cases or those with MEN2 phenotype (pheochromocytoma, medullary thyroid carcinoma) — MEN2A screening recommended in RET-positive Hirschsprung patients

— Other genes: EDNRB, EDN3, SOX10, GDNF

— Echocardiogram and chromosomal microarray/karyotype if Down syndrome features

— Hearing screen (Waardenburg, syndromic forms)

— Urinary metanephrines / calcitonin if RET mutation identified (lifelong MEN2 surveillance)

Key distinction: Anorectal manometry screens (absent RAIR → suggestive), contrast enema localizes (transition zone), but only rectal biopsy with absent ganglion cells + hypertrophied nerves + AChE/calretinin pattern establishes the diagnosis. Step 3 frequently tests this hierarchy.

Rectal biopsy — gold standard for diagnosis:

Histopathologic findings (the diagnostic triad):

Newer ancillary stains:

Genetic testing:

Workup of associated conditions (do not skip):

Risk Stratification and Initial Management Logic

— NPO, place nasogastric tube for decompression

— IV fluid resuscitation (isotonic crystalloid; correct electrolytes, especially Na/K)

— Broad-spectrum antibiotics if any signs of enterocolitis or sepsis: ampicillin + gentamicin + metronidazole (or piperacillin-tazobactam)

— Serial abdominal exams; surgical consult early

— Rectal irrigations with warm saline (10 mL/kg) 2–3 times daily via a soft rectal tube passed above the transition zone

— Goal: evacuate stool/gas, prevent and treat HAEC, allow bowel wall edema to resolve

— Avoid enemas with tap water (hyponatremia risk) or hypertonic phosphate (hyperphosphatemia, hypocalcemia in neonates)

— Timing has shifted: primary single-stage pull-through in the neonatal period (3–6 months of age, weight ~5 kg) is now standard in stable infants

— Staged approach with initial leveling colostomy reserved for:

— Severe enterocolitis or perforation

— Massively dilated proximal bowel that won't decompress

— Long-segment or total colonic disease

— Delayed diagnosis with malnutrition

— Length of aganglionic segment (short < long < total colonic — worsening prognosis)

— Presence of HAEC at diagnosis (recurrence risk post-op)

— Down syndrome — higher HAEC rates, worse continence outcomes

— Nutritional status, age at diagnosis

CCS pearl: On a CCS-style case, the neonate with delayed meconium and a transition zone on contrast enema gets: NPO, IVF, NG decompression, rectal irrigations, surgery consult, suction rectal biopsy, and (if HAEC) IV antibiotics — sequence these orders before jumping to "schedule pull-through."

Step 1 — Stabilize:

Step 2 — Decompress the obstruction:

Step 3 — Confirm diagnosis with rectal biopsy as above

Step 4 — Definitive surgical repair (pull-through procedure):

Risk stratification factors:

Pharmacotherapy and Preoperative Medical Management

— First-line empiric regimen: IV broad-spectrum coverage for gram-negative, gram-positive, and anaerobic enteric flora

— Ampicillin + gentamicin + metronidazole (classic neonatal regimen)

— Or piperacillin-tazobactam monotherapy in stable older children

— Add vancomycin if MRSA risk or critical illness

— Oral metronidazole (15–30 mg/kg/day divided q8h) for mild-to-moderate HAEC or maintenance prophylaxis in high-risk infants

— Oral vancomycin added if recurrent or refractory HAEC, especially if Clostridioides difficile is isolated

— Duration: 7–14 days for acute episode

— Warm normal saline 10–20 mL/kg via soft red rubber catheter, 2–4 times daily

— Taught to parents pre-op and continued post-op as prophylaxis against HAEC for several months

— Aggressive crystalloid resuscitation in sepsis; correct hyponatremia, hypokalemia, metabolic acidosis

— Monitor for third-spacing in distended bowel

— TPN if prolonged NPO or malnutrition before surgery

— Advance enterally once obstruction resolved and bowel function returns

— Some pediatric surgery centers use probiotics (Lactobacillus species) to reduce HAEC recurrence — evidence is mixed, not yet standard of care, but appears on board questions

— Loperamide, codeine, opioids — worsen obstruction and mask perforation

— Hypertonic phosphate enemas in neonates — risk of fatal hyperphosphatemia, hypocalcemic tetany

— Bulk-forming laxatives preoperatively — can worsen obstruction

Board pearl: Recurrent or severe HAEC, especially post-pull-through, raises concern for retained aganglionic segment, anastomotic stricture, or internal sphincter achalasia — escalate evaluation rather than just re-treating with antibiotics.

Antibiotics for Hirschsprung-Associated Enterocolitis (HAEC):

Rectal irrigation regimen (cornerstone of medical management):

Fluid and electrolyte management:

Nutritional support:

Probiotics:

Drugs to AVOID or use cautiously:

Surgical Management — Pull-Through Procedures

— Intraoperative seromuscular biopsies confirm where ganglion cells return — defines the resection margin (the "transition zone" must be fully resected plus a normoganglionic margin)

— Swenson: original procedure — resects aganglionic rectum down to internal sphincter, end-to-end anastomosis. Effective but technically demanding; risk of pelvic nerve injury (urinary/sexual dysfunction)

— Duhamel: retrorectal pull-through, side-to-side anastomosis between normal colon and aganglionic rectum, creating a neorectum. Lower pelvic nerve injury risk; potential fecaloma in residual rectal stump

— Soave (endorectal pull-through): mucosectomy of the aganglionic rectum with pull-through of normal colon inside a muscular cuff. Most commonly performed today, often via transanal approach with or without laparoscopic assist

— Single-stage, no abdominal incision for short-segment disease

— Shorter hospital stay, less adhesion risk, good cosmetic outcome — now preferred where feasible

— Initial leveling colostomy at the most distal point with ganglion cells (confirmed by frozen-section biopsy)

— Definitive pull-through at 3–6 months

— Colostomy closure as third stage (in 3-stage approach)

— May require ileoanal pull-through or modifications (Martin, Kimura procedures)

— Higher rates of stooling difficulty, enterocolitis, and need for permanent ileostomy

— Anastomotic leak, pelvic abscess, wound infection

— Early HAEC — continue rectal irrigations and watch for fever/distention/diarrhea

Step 3 management: A toddler 6 months post-Soave with persistent obstructive symptoms — first evaluate for anastomotic stricture (DRE, contrast study), retained transition zone (repeat biopsy), or internal sphincter achalasia (treat with botulinum toxin injection or anorectal myectomy) before assuming dysmotility.

Definitive treatment is surgical resection of the aganglionic segment with anastomosis of normally innervated bowel to the anus

Preoperative leveling:

Three classic single-stage pull-through procedures:

Transanal endorectal pull-through (TEPT):

Staged approach (when used):

Long-segment / total colonic aganglionosis:

Post-op early issues:

Special Populations — Renal/Hepatic Considerations and Older Patients

— Almost always ultra-short-segment disease missed in infancy

— Lifelong constipation, laxative dependence, recurrent impaction, megacolon on imaging

— Workup: anorectal manometry (absent RAIR), full-thickness rectal biopsy

— Treatment options: posterior internal sphincter myectomy for ultra-short segment, or formal pull-through if longer involvement

— Avoid aminoglycosides (gentamicin) in renal dysfunction — substitute with cefotaxime or piperacillin-tazobactam for HAEC coverage

— Dose-adjust vancomycin, piperacillin-tazobactam by renal function

— Avoid hypertonic phosphate enemas — risk of acute phosphate nephropathy and life-threatening electrolyte derangement in patients with CKD, dehydration, or in young children

— Metronidazole accumulates in severe hepatic dysfunction — reduce dose by 50% in Child-Pugh C

— TPN-associated cholestasis in long-segment disease or prolonged NPO — monitor liver enzymes, conjugated bilirubin; use lipid-minimization or fish-oil-based emulsions

— Total colonic aganglionosis post-pull-through may develop short bowel syndrome with malabsorption, B12 deficiency, fat-soluble vitamin deficiency, oxalate kidney stones

— Monitor electrolytes, vitamins, growth long-term

— Screen for associated genitourinary anomalies (renal agenesis, vesicoureteral reflux) with renal ultrasound when other anomalies are present

Key distinction: A teenager with lifelong constipation and an empty rectum on DRE likely has ultra-short-segment Hirschsprung or internal anal sphincter achalasia, not functional constipation — both lack the RAIR on manometry. Distinction requires biopsy (ganglion cells present in achalasia, absent in Hirschsprung).

Adolescent/adult presentation of Hirschsprung:

Renal impairment considerations:

Hepatic impairment:

Patients with prior bowel surgery / short gut:

Renal anomalies are over-represented:

Special Populations — Syndromic Associations and Pediatrics

— Present in ~10% of Hirschsprung cases; conversely, ~3% of Down patients have Hirschsprung

— Higher rates of HAEC, post-op enterocolitis, and fecal incontinence after pull-through

— Screen any neonate with Down syndrome and delayed stooling or constipation aggressively

— Coordinate with cardiology (AV canal defect), endocrinology (hypothyroidism), and developmental services

— Long-segment Hirschsprung can be the first manifestation of a RET proto-oncogene mutation

— Patients with germline RET mutation need lifelong screening for medullary thyroid carcinoma (calcitonin, prophylactic thyroidectomy in childhood) and pheochromocytoma (plasma/urine metanephrines)

— Genetic counseling is essential — autosomal dominant inheritance with variable penetrance

— Hirschsprung + sensorineural deafness + pigmentary abnormalities (white forelock, heterochromia, leukoderma)

— EDNRB, EDN3, or SOX10 mutations

— PHOX2B mutation; central apnea + Hirschsprung — requires home ventilation, sleep medicine involvement

— Diagnosis is harder — delayed meconium passage is common in preterm infants without Hirschsprung

— Hold definitive surgery until adequate weight/maturity; manage with irrigations

— Adult women with prior pull-through can have successful pregnancies; vaginal delivery generally acceptable, but obstetric consult for those with significant perineal scarring or continence issues — C-section may be preferred for total colonic aganglionosis patients with ileoanal anastomosis

Board pearl: Any patient with long-segment Hirschsprung, family history of Hirschsprung, or a thyroid mass should have RET testing. A missed RET mutation = missed MEN2A = missed medullary thyroid cancer screening — a classic Step 3 cause-and-effect linkage.

Down syndrome (Trisomy 21):

MEN2A and RET mutations:

Waardenburg-Shah syndrome (Type 4):

Congenital central hypoventilation (Haddad syndrome):

Prematurity:

Pregnancy:

Complications and Adverse Outcomes

— Occurs in 20–50% of patients, pre- or post-operatively

— Pathogenesis: stasis → bacterial overgrowth → mucosal invasion → bacterial translocation → sepsis

— Highest risk in first 2 years post-pull-through, in Down syndrome, long-segment disease, and trisomy 21

— Presentation: fever, abdominal distention, foul/bloody explosive diarrhea, lethargy, shock

— Mortality up to 30% if delayed recognition

— Massive dilation, ischemia, perforation — surgical emergency requiring laparotomy and possible diverting ostomy

— Anastomotic leak (early) — sepsis, abscess; may require diverting stoma

— Anastomotic stricture — recurrent obstruction; managed with anal dilations or surgical revision

— Retained aganglionic segment / transition zone — persistent obstructive symptoms; diagnosed by repeat biopsy, treated by redo pull-through

— Internal anal sphincter achalasia — sphincter fails to relax; treated with botulinum toxin injection or posterior anal myectomy

— Pelvic nerve injury (Swenson > Duhamel > Soave) — urinary retention, sexual dysfunction

— Fecal incontinence / soiling — 10–30%, more common in long-segment and Down syndrome

— Chronic constipation post-pull-through — 10–30%

— Dysmotility and bloating

— Need for ongoing bowel management programs (laxatives, enemas, biofeedback)

— Short bowel syndrome after extensive resection; failure to thrive in untreated disease

— School absenteeism, body image issues, anxiety related to soiling — refer to pediatric psychology

Step 3 management: Suspected HAEC = immediate NPO, IVF, NG decompression, broad-spectrum IV antibiotics with metronidazole, rectal irrigations, and surgical reassessment — do not wait for stool studies to start treatment.

Hirschsprung-Associated Enterocolitis (HAEC) — the most feared complication:

Toxic megacolon and perforation:

Postoperative complications:

Long-term functional outcomes:

Nutritional/growth:

Psychosocial:

Escalation of Care — ICU, Consults, and Inpatient Triage

— Septic shock from HAEC — vasopressor requirement, lactic acidosis, multi-organ dysfunction

— Toxic megacolon with hemodynamic instability

— Perforation requiring emergent laparotomy

— Severe electrolyte disturbances (Na <125, K <2.5 or >6.5) needing close monitoring

— Post-operative respiratory compromise, especially in syndromic infants (Down, Haddad)

— Pediatric surgery — primary team; involve at first suspicion, do not wait for biopsy

— Neonatology / pediatric hospitalist — co-management of medical issues

— Pediatric gastroenterology — biopsy interpretation, motility studies, long-term bowel management

— Genetics — RET testing, syndromic evaluation, family counseling

— Cardiology — echo if Down syndrome or other anomalies suspected

— Pediatric anesthesia — preoperative airway evaluation in syndromic patients

— Stoma nurse / WOCN — preoperative teaching for families when staged repair planned

— Social work / care coordination — discharge planning, equipment (irrigation supplies)

— Q2–4h vitals; abdominal exam q4h

— Strict I/Os, daily weights

— NG to low intermittent suction with output monitoring

— Rectal irrigations as ordered, document output

— Glucose checks in neonates

— Free air on imaging

— Peritonitis on exam

— Refractory HAEC failing 24–48 hours of medical therapy

— Rapidly worsening sepsis despite resuscitation

— Community hospitals without pediatric surgery should stabilize and transfer to tertiary center with neonatal/pediatric surgical capability — do not delay for completion of imaging

CCS pearl: On a CCS case of suspected HAEC, simultaneously order IV access, fluids, NG, labs, blood/stool cultures, antibiotics, abdominal X-ray, and the pediatric surgery consult — don't sequence them serially. The clock advances and the patient deteriorates if you wait.

Indications for PICU/NICU admission:

Consults to mobilize:

Inpatient triage on the floor:

When to take to OR emergently:

Transfer considerations:

Key Differentials — Other Causes of Neonatal Bowel Obstruction

— >90% associated with cystic fibrosis

— Thick, inspissated meconium obstructs terminal ileum

— Contrast enema: microcolon (unused distal colon) with inspissated meconium pellets in terminal ileum

— Treatment: gastrografin enema (therapeutic and diagnostic); surgery if fails or perforated

— Always sweat chloride test and CFTR genetic testing

— Transient obstruction by a meconium plug, usually in left colon

— Associated with maternal diabetes, magnesium therapy (preeclampsia treatment), prematurity, hypothyroidism

— Contrast enema is diagnostic and therapeutic — plug passes, symptoms resolve

— Still get rectal biopsy if symptoms persist or recur — meconium plug can be the presenting feature of Hirschsprung

— Absent or abnormally located anal opening on perineal exam — inspect every newborn perineum

— Associated with VACTERL — vertebral, anal, cardiac, tracheoesophageal, renal, limb anomalies — screen accordingly

— Duodenal atresia: "double bubble" sign, associated with Down syndrome (30%), polyhydramnios

— Jejunoileal atresia: vascular accident in utero

— Bilious vomiting in a previously well neonate is malrotation until proven otherwise — surgical emergency

— Upper GI series: corkscrew duodenum, abnormal ligament of Treitz position

— Premature infant, feeding intolerance, bloody stools, pneumatosis intestinalis on X-ray

— Treatment: NPO, IV antibiotics, surgical consult; not surgical unless perforation

Key distinction: Meconium ileus = microcolon + ileal pellets + CF; Meconium plug = left colon plug + maternal diabetes/Mg; Hirschsprung = transition zone + rectosigmoid ratio <1 + absent ganglion cells. Step 3 stems hinge on which clue is emphasized.

Meconium ileus:

Meconium plug syndrome (functional immaturity of colon):

Imperforate anus / anorectal malformations:

Intestinal atresia (duodenal, jejunal, ileal):

Malrotation with midgut volvulus:

Necrotizing enterocolitis (NEC):

Key Differentials — Other-Category Causes of Constipation

— Onset after toilet training, dietary transitions, or stressful events — NOT from birth

— Stool withholding behavior, encopresis, painful defecation

— DRE: rectum full of stool, normal anal tone

— Treatment: disimpaction + maintenance polyethylene glycol (PEG 3350), behavioral interventions, dietary fiber

— Constipation, lethargy, poor feeding, macroglossia, prolonged jaundice, hypothermia

— Newborn screen — TSH, free T4

— Treatment: levothyroxine

— Constipation, polyuria, lethargy

— Causes: Williams syndrome (idiopathic infantile hypercalcemia + elfin facies + supravalvular AS), vitamin D excess, hyperparathyroidism

— Sacral dimple, hair tuft, hemangioma, asymmetric gluteal cleft, absent anal wink, lower extremity weakness

— MRI lumbosacral spine

— Constipation or hematochezia in infants; resolves with hydrolyzed formula

— Constipation, irritability, developmental regression, microcytic anemia with basophilic stippling

— Opioids, anticholinergics, iron supplementation, sucralfate

— Constipation is often the first symptom, followed by descending flaccid paralysis, poor feeding, weak cry; honey exposure history

— Treatment: BabyBIG (human botulism immune globulin IV)

— Distal intestinal obstruction syndrome (DIOS) — recurrent obstruction in known CF patients

Board pearl: A neonate with constipation + hypotonia + weak cry + poor feeding — think infant botulism, not Hirschsprung. Order stool toxin/organism testing and treat empirically with BabyBIG; honey history is suggestive but not always present.

Functional constipation (most common cause of pediatric constipation):

Hypothyroidism (congenital or acquired):

Hypercalcemia:

Spinal cord pathology — tethered cord, sacral agenesis, spina bifida:

Cow's milk protein allergy:

Lead toxicity:

Medication-induced:

Botulism (infant):

Cystic fibrosis (older child):

Secondary Prevention, Discharge Planning, and Long-Term Care

— Tolerating enteral feeds with appropriate weight gain

— Stooling pattern established (often loose/frequent initially)

— Parents demonstrate competency with rectal irrigations and HAEC recognition

— Pain controlled on oral analgesics

— Follow-up appointments arranged

— Routine postoperative rectal irrigations for 6–12 months (often daily, then weaning) — single most evidence-supported intervention to reduce HAEC

— Consider oral metronidazole prophylaxis in high-risk patients (Down syndrome, long-segment disease, recurrent HAEC)

— Probiotics — center-dependent

— Stool softeners (PEG 3350) titrated to soft formed stool

— Fiber supplementation in older children

— Loperamide cautiously in post-op high-output stooling (only after HAEC excluded)

— Scheduled toilet sits, biofeedback for older children with incontinence

— HAEC warning signs: fever, abdominal distention, foul/explosive diarrhea, lethargy, blood in stool → return to ED immediately

— How to perform rectal irrigations

— Skin care for perineal dermatitis (very common post-pull-through)

— Diet advancement plan

— Catch up routine pediatric vaccines on schedule; no contraindication to live vaccines from Hirschsprung itself

— RET-positive patients: lifelong MEN2A screening — annual calcitonin, plasma metanephrines, consideration of prophylactic thyroidectomy in childhood

— Down syndrome — standard health supervision (thyroid, hearing, vision, cardiac, atlantoaxial)

Step 3 management: On discharge after pull-through, schedule pediatric surgery follow-up in 1–2 weeks for wound check and anal exam, pediatrician in 1 week, and arrange anal dilations per surgeon protocol to prevent anastomotic stricture — a frequently missed item.

Discharge criteria after pull-through:

HAEC prophylaxis after surgery:

Bowel management program:

Family education at discharge — must document:

Immunizations:

Genetic and syndromic follow-up:

Follow-Up, Monitoring, and Rehabilitation

— Pediatric surgery: 1–2 weeks post-op, then 1, 3, 6, and 12 months, then annually for at least 5 years

— Anorectal exam at each visit in the first year — assess for stricture, perform calibrated dilations

— Pediatrician: integrate growth monitoring, vaccinations, developmental screening

— Pediatric GI / motility clinic: referral for ongoing constipation, incontinence, or recurrent HAEC

— Growth: height, weight, BMI at every visit — failure to thrive prompts nutrition and re-evaluation for retained aganglionic segment

— Stool diary: frequency, consistency, soiling episodes

— Quality-of-life and continence scoring (e.g., Krickenbeck classification) in school-age children

— Started ~2 weeks post-op, performed by parents at home with Hegar dilators

— Frequency decreases over months; prevents anastomotic stricture

— Daily enema-based regimens for soiling/incontinence

— Antegrade continence enemas (ACE / Malone procedure) in refractory cases — appendicostomy allows flushes from above

— Biofeedback therapy for older children with retentive behavior or pelvic floor dyssynergia

— High-fiber diet, adequate hydration

— Iron, B12, fat-soluble vitamin monitoring in long-segment/total colonic disease

— School accommodations for bathroom access

— Pediatric psychology for body image, anxiety, school refusal related to soiling

— Connection with parent support groups

Board pearl: Recurrent post-pull-through obstructive symptoms warrant a systematic workup: DRE for stricture → contrast study → repeat rectal biopsy to rule out retained aganglionic segment, and anorectal manometry/EUA for internal sphincter achalasia. Don't just keep prescribing laxatives.

Follow-up cadence:

Monitoring parameters:

Anal dilation program:

Bowel management for chronic stooling problems:

Nutrition counseling:

Psychosocial / school support:

Ethical, Legal, and Patient Safety Considerations

— Both parents (or legal guardian) must understand: diagnosis, alternatives (staged vs. single-stage pull-through), risks (incontinence, infertility from pelvic nerve injury, recurrent HAEC, need for permanent stoma), and lifelong implications including future fertility/sexual function

— Use of professional medical interpreters mandatory for non-English-speaking families — never use family members for consent discussions

— Some families (e.g., Jehovah's Witness) decline blood transfusion — preoperative planning with erythropoietin, iron optimization, cell salvage techniques, and clear documentation of refusal; involve ethics committee proactively

— In emergent life-threatening situations involving a minor, court order can authorize transfusion if parents refuse

— Severe failure to thrive due to delayed presentation in a school-age child with classic findings since birth — assess for medical neglect; report to child protective services if there is a pattern of missed appointments and inadequate care

— NICU/PICU to floor: ensure NG output, irrigation orders, and HAEC precautions are transmitted in structured handoff (SBAR/I-PASS)

— Inpatient to outpatient: verify follow-up appointments scheduled before discharge, not just recommended — closed-loop communication

— Pediatric to adult care transition (adolescents): structured transition program by age 18, transfer of MEN2A surveillance if applicable

— Pre-op timeout, surgical site marking, antibiotic prophylaxis within 60 min of incision

— VTE prophylaxis in adolescents/young adults

— Avoid hypertonic phosphate enemas in children <2 years — institutional protocols should prohibit

— RET testing results — handle per GINA (Genetic Information Nondiscrimination Act); counsel family on implications for siblings and reproductive choices

Step 3 management: A 6-week-old with new HAEC discharged 3 days ago without scheduled follow-up represents a transition-of-care failure. Root cause analysis should examine discharge checklist, family teach-back, and appointment confirmation — all preventable system errors.

Informed consent in neonatal surgery:

Cultural and religious considerations:

Mandated reporting:

Transitions of care — high-risk handoffs:

Patient safety bundles:

Genetic information privacy:

High-Yield Associations and Rapid-Fire Clinical Facts

— Down syndrome (Trisomy 21) — 10% of Hirschsprung cases; worse outcomes

— RET proto-oncogene — long-segment disease, MEN2A risk → screen for medullary thyroid cancer, pheochromocytoma

— EDNRB/EDN3 — Waardenburg-Shah syndrome (Type 4): deafness + pigment defects

— PHOX2B — Haddad syndrome (central hypoventilation)

— L1CAM — Hirschsprung with hydrocephalus

— Incidence 1:5,000; male:female 4:1 (narrows in long-segment to 1:1)

— 80% short-segment (rectosigmoid), 15% long-segment, 5% total colonic

— Familial recurrence risk: 4% (varies with sex of proband and length of segment)

— Neural crest cell migration fails in craniocaudal direction — explains why aganglionosis always starts distally and extends proximally, never skip lesions

— Absent ganglion cells + hypertrophied nerve trunks + increased AChE staining (or absent calretinin)

— Contrast enema transition zone, rectosigmoid ratio <1, 24-hour retained contrast

— Plain film: distal bowel gas paucity, proximal dilation

— Absent rectoanal inhibitory reflex (RAIR) — internal sphincter doesn't relax

— Suction rectal biopsy = diagnostic gold standard

— Soave (transanal endorectal pull-through) — most common modern operation

— Rectal irrigations = mainstay medical therapy pre- and post-op

— HAEC = leading cause of morbidity/mortality

— "HIM-A" — Hirschsprung, Imperforate anus, Meconium ileus/plug, Atresia (intestinal), plus malrotation, hypothyroidism, sepsis

Board pearl: "Bilious vomiting in a newborn" + delayed meconium + abdominal distention + Down syndrome features → think Hirschsprung first, duodenal atresia second (double bubble would be on the X-ray for duodenal atresia). Always image before committing.

Genetic and syndromic associations:

Epidemiology pearls:

Embryology:

Histology triad:

Imaging signatures:

Manometry:

Treatment landmarks:

Differential mnemonic for delayed meconium:

Board Question Stem Patterns

— "A term male newborn has not passed meconium at 50 hours of life. He has abdominal distention and bilious emesis. Rectal exam reveals a tight anal canal with explosive release of stool and gas upon withdrawal of the finger." → Diagnosis: Hirschsprung; next step: contrast enema; gold standard: suction rectal biopsy

— Newborn with hypotonia, flat facies, single palmar crease, delayed meconium, and AV canal murmur → screen aggressively for Hirschsprung; karyotype and echocardiogram

— 4-month-old s/p pull-through with fever, abdominal distention, foul explosive diarrhea, lethargy → diagnosis HAEC; first step: IV fluids, NPO, NG decompression, broad-spectrum antibiotics with metronidazole, rectal irrigations

— "Newborn with abdominal distention, no meconium, and family history of recurrent pulmonary infections" → meconium ileus / CF; contrast enema shows microcolon with ileal pellets

— "5-year-old with constipation since birth, ribbon stools, FTT, empty rectum on DRE" → Hirschsprung

— Contrast: "5-year-old with constipation since toilet training, encopresis, rectum full of stool" → functional constipation

— Child with long-segment Hirschsprung and family history of thyroid cancer → RET mutation testing; screen for medullary thyroid carcinoma and pheochromocytoma

— Toddler 8 months post-pull-through with persistent obstructive symptoms → DRE for stricture → contrast study → repeat biopsy for retained aganglionic segment → consider internal sphincter achalasia (botulinum toxin)

— Phosphate enema given to a neonate → hyperphosphatemia, hypocalcemic tetany, AKI — wrong answer; correct: warm saline irrigation

Key distinction: When the stem emphasizes "since birth" + "empty rectum" + "squirt sign", the answer is always Hirschsprung. When the stem emphasizes "after toilet training" + "encopresis" + "stool in rectum", the answer is functional constipation. Step 3 loves this binary.

Classic neonatal stem:

Down syndrome variant:

HAEC stem:

Differential trap — meconium ileus vs. Hirschsprung:

Older child with chronic constipation:

MEN2 linkage:

Post-op complication stem:

Drug safety distractor:

One-Line Recap

Hirschsprung disease is congenital distal-bowel aganglionosis presenting with delayed meconium passage and chronic constipation from birth; it is confirmed by rectal biopsy showing absent ganglion cells with hypertrophied nerve trunks and treated definitively by surgical pull-through, with vigilance for Hirschsprung-associated enterocolitis as the leading cause of morbidity and mortality.

— Clinical: delayed meconium >48 hours, empty rectal vault, squirt sign on DRE

— Imaging: contrast enema with transition zone and rectosigmoid ratio <1

— Pathology: suction rectal biopsy — absent ganglion cells, hypertrophied nerve trunks, increased AChE / absent calretinin

— Stabilize (NPO, IVF, NG decompression) → decompress (rectal irrigations) → diagnose (biopsy) → definitive (Soave/Duhamel/Swenson pull-through, often single-stage transanal endorectal) → prevent HAEC (irrigations ± metronidazole)

— Fever + distention + foul explosive diarrhea = immediate IV antibiotics, irrigations, surgical consult; can occur pre- or post-op, recurrent episodes prompt evaluation for retained segment or sphincter achalasia

— Down syndrome (10%), RET mutations → MEN2A screening, Waardenburg-Shah, Haddad (PHOX2B) — and always distinguish from functional constipation (onset after toilet training, encopresis, rectum full of stool)

Board pearl: If a Step 3 stem mentions delayed first meconium passage, the answer involves Hirschsprung until proven otherwise — work up before discharge, even if the infant looks well, because the next encounter may be septic HAEC.

Diagnosis triad to memorize:

Management cascade:

HAEC = the killer:

Don't-miss associations: