Hirschsprung disease (HD)

Epidemiology

• Most Common lower intestinal obstruction in neonates
• 1 in 5000 live births
• M > F  (2-4x)
  

Pathology

• Rectal Biopsies show:
• Decreased or absent calretinin-immunoreactive fibers in the lamina propria
• Absence of ganglion cells in the rectal mucosa and submucosa (absence of Meissners and Auerbachs plexuses)
• Hypertrophic nerve fibers/bundles with high concentration of acetylcholinesterase activity or staining between the muscular layers and within the submucosa
  

Genetics

• Usually sporadic, but both dominant and recessive inheritance seen in family groups
• Assoc w/ multiple congenital anomalies (hydronephrosis, astigmatism)
• 16% of HD patients have Down syndrome ( but <1% of Down syndrome pts have HD)
• RET proto-oncogene in the predominant gene affected. Mutations of this gene leads to a loss of function of the RET receptor tyrosine kinase, which causes impaired migration and differentiation of the neural crest cells that give rise to the enteric nervous system. Genes affected include:
  
• RET signaling pathway (RET, GDNF, and NTN)
• Endothelin (EDN) Type B receptor pathway (EDNRB, EDN3, and EVE-1)
• Syndromic forms assoc w/ L1CAM, SOX10 and ZFHX1B
  

Clinical Manifestations

• HD should be suspected in:
• Any full-term neonate with delayed passage of stool x 48hrs (rare in preterm infants)
• Infants with constipation despite normal passage of meconium w/i 48hrs
• Note: only 45-90% of infants with HD fail to pass mec in the first 48hrs (10-55% do pass mec)
  
• Classic progression
• Failure to pass stool -->Abdominal Distension-->Bilious Vomiting
• If not recognized can progress to Toxic megacolon, enterocolitis (HAEC), Diarrhea, sepsis, perforation
• Breastfed infants can present less severe
• Red Flags
• Delayed passage of meconium
• Abdominal distension relieved by digital rectal stimulation/enema
  
• Neonatal intestinal obstruction (bilious vomiting)
  
• Chronic severe constipation not responding well to medical therapy
  
• Enterocolitis
  
• Bowel perforation
• Physical Exam
• Abdominal distention (tympanic with palpable stool in LLQ)
  
• Tight/snug anal sphincter with narrow rectum
• Squirt sign, withdrawal of the finger during rectal exam produces explosive expulsion of foul smelling gas/stool
• Stool can be described as pellets, ribbons, or liquid (unlike large stool of functional constipation)
  

Diagnosis

• Anorectal manometry (ARM) - Eliciting a rectoanal inhibitory reflex (RAIR) excludes HD
• Diagnosis can only be made by Rectal Biopsy (suction Bx or full thickness Bx)
• biopsies need to be obtained >2cm proximal to the dentate line (normal area of hypoganlionosis occurs within 3-17mm of the dentate line)
• Contrast Enema can support the diagnosis if an abrupt transition zone is seen between the narrow aganglionic segment and the proximal dilated colon. If no transition zone is seen, a rectal diameter the same size or smaller than the sigmoid colon suggests HD
  
• Best results occur when patient is unprepped and older then 1mo (dilation is less likely in the 1st few wks of life)
• 10% of HD pts have a "normal" contrast enema (false neg, prepped, post-rectal exam, long segment)
  
• For "normal" studies, a 24hr delayed plain film can showed retained contrast
  
• 10% patients Dx >3yo (Typically with constipation or FTT)

Ultra-short segment HD - also called anal achalasia. Normal rectal biopsies but failure to relax anal sphincter (RAIR) on ARM. Treat with Anal Botox

Differential Diagnosis (neonates)

• Meconium plug syndrome
• Meconium ileus
• Intestinal Atresia
• Currino Triad
• Anorectal Malformations (ectopic anus, anal stenosis, imperforate anus)
• Sacral Bone Anomalies (Hypoplasia, poor segmentation)
• Presacral anomly (anterior meningoceles, teratoma, cyst)
  

• Surgery
• Diversion followed by correction
• Primary pull through (now Standard of Care unless there is enterocolitis)
  
• Swenson (technically difficult)
• Duhamel pouch
• Soave cuff
  

• NPO
• IVF
• IV ABX
• Rectal Irrigation
• Surgical Consult - consider colostomy