#48 – Hirschsprung Disease



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Pathophysiology

  • Motor gut disorder characterized by failure of the neural crest cells (which are precursors to the enteric ganglion cells) to fully migrate to the distal portions of the colon.
    • Most accepted theory is there is a defect in the craniocaudal migration of neuroblasts that occurs between 4-7 weeks gestation
      • 12 genetic mutations currently identified predominantly affecting the RET proto-oncogene
        • Produces a tyrosine kinase protein that transduces growth and differentiation signals in developing tissues
  • The absence of these cells in the mucosal and muscular layer of the colon results in the failure of the colonic muscles to relax.

Epidemiology

  • Occurs in 1:5000 live births
  • Male:Female ratio of 3-4:1
  • 80% of cases affect the rectosigmoid junction (termed short-segment disease)
  • 15-20% of cases extend to the proximal sigmoid colon (termed long-segment disease)
  • <5% of cases affect the entire colon

Associated Syndromes

  • Trisomy 21(up to 16% of cases)
  • Bardet-Biedi
  • Cartilage-hair hypoplasia
  • Congenital central hypoventilation syndrome
  • Familial dysautonomia
  • Multiple endocrine neoplasia type 2
  • Mowat-Wilson
  • Smith-Lemli-Opitz
  • Waardenburg

Associated Congenital Anomalies

Up to 25% of Hirschsprung patients have other congenital anomalies including:

  • Genitourinary (20-40%)
    • Hydronephrosis, renal agenesis
  • Visual/Hearing Impairment (5-40%)
    • Most are refractive errors
  • Congenital Heart Disease (50%)
    • Almost exclusively in syndromic Hirschsprung
  • Anorectal Malformations

Signs and Symptoms

  • Failure to pass meconium in first 48 hours
    • 100% of normal full-term infants pass meconium in first 48 hours in contrast to only 10-40% of infants with Hirschsprung
  • Abdominal distention
    • Squirt/Blast Sign
      • Explosive expulsion of gas and stool after digital rectal examination
  • Bilious emesis
  • Enterocolitis and volvulus are rare, life-threatening complications or presentations
  • Most are diagnosed in the neonatal period, but less-severe short-segment disease can present as late as 3 years old

Diagnostic Work-Up

  • Indications for testing include:
    • Symptoms of obstruction
    • Failure to pass meconium after 48 hours
    • Constipation and Trisomy 21 (or other associated syndrome)
    • Constipation and physical examination suggestive of Hirschsprung
  • If fever, lethargy, and/or obstipation are present, emergent evaluate for enterocolitis is needed
  • Studies
    • “Unprepped” contrast enema
      • Identification of transition zone
        • Change from normal caliber/narrowed rectum to dilated proximal colon
  • Anorectal manometry
    • Useful in ultrashort segment disease
    • Can approach 100% NPV is performed properly
    • Suction rectal biopsy
      • GOLD STANDARD for diagnosis
      • Location should be 2cm above the level of the dentate line
  • Histology findings
    • Presence of hypertrophic nerve fibers
    • Increased acetylcholinesterase activity or staining in the muscularis mucosae
    • Decreased or absent calretinin-immunoreactive fibers in the lamina propria
Abnormal acetylcholine esterase (AchE)-positive nerve fibers (brown) in the mucosa


Treatment

  • Surgery is the mainstay of treatment
    • Resect the affected segment
    • Bring the normal ganglionic bowel down to anus
    • Preserve internal sphincter function
  • Originally, this was an open, two-stage procedure with a diverting colostomy
    • To allow the dilated segement to decompress back to normal size
  • Now, it can be performed as a single-stage operation either laparoscopically or transanally
  • 3 types of Pull-Through Procedures
  • Complications
    • Anastomotic stricture, constipation, incontinence, or enterocolitis

The Cottage Physician (1893)

Chapter – Children and Their Diseases


References

  1. Hoffenberg EJ, Furuta GT, Kobak G, Walker T, Soden J, Kramer RE, Brumbaugh D. Gastrointestinal Tract. In: Hay, Jr. WW, Levin MJ, Deterding RR, Abzug MJ. eds. Current Diagnosis & Treatment: Pediatrics, 24e New York, NY: McGraw-Hill
  2. Badner JA, Sieber WK, Garver KL, Chakravarti A. A genetic study of Hirschsprung disease. American journal of human genetics. 1990; 46(3):568-80. [pubmed]
  3. Fu M, Tam PK, Sham MH, Lui VC. Embryonic development of the ganglion plexuses and the concentric layer structure of human gut: a topographical study. Anatomy and embryology. 2004; 208(1):33-41. [pubmed]
  4. Goldstein AM, Hofstra RM, Burns AJ. Building a brain in the gut: development of the enteric nervous system. Clinical genetics. 2013; 83(4):307-16. [pubmed]
  5. Amiel J, Sproat-Emison E, Garcia-Barcelo M, et al. Hirschsprung disease, associated syndromes and genetics: a review. Journal of medical genetics. 2008; 45(1):1-14. [pubmed]
  6. Pini Prato A, Rossi V, Mosconi M, et al. A prospective observational study of associated anomalies in Hirschsprung’s disease. Orphanet journal of rare diseases. 2013; 8:184. [pubmed]
  7. Sarioglu A, Tanyel FC, Büyükpamukçu N, Hiçsönmez A. Hirschsprung-associated congenital anomalies. European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery … [et al] = Zeitschrift fur Kinderchirurgie. 1997; 7(6):331-7. [pubmed]
  8. Khan AR, Vujanic GM, Huddart S. The constipated child: how likely is Hirschsprung’s disease? Pediatric surgery international. 2003; 19(6):439-42. [pubmed]
  9. Arshad A, Powell C, Tighe MP. Hirschsprung’s disease. BMJ (Clinical research ed.). 2012; 345:e5521. [pubmed]
  10. Evaluation and treatment of constipation in infants and children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Journal of pediatric gastroenterology and nutrition. 2006; 43(3):e1-13. [pubmed]
  11. Putnam LR, John SD, Greenfield SA, et al. The utility of the contrast enema in neonates with suspected Hirschsprung disease. Journal of pediatric surgery. 2015; 50(6):963-6. [pubmed]
  12. Meinds RJ, Trzpis M, Broens PMA. Anorectal Manometry May Reduce the Number of Rectal Suction Biopsy Procedures Needed to Diagnose Hirschsprung Disease. Journal of pediatric gastroenterology and nutrition. 2018; 67(3):322-327. [pubmed]
  13. Alizai NK, Batcup G, Dixon MF, Stringer MD. Rectal biopsy for Hirschsprung’s disease: what is the optimum method? Pediatric surgery international. 1998; 13(2-3):121-4. [pubmed]
  14. Hackam DJ, Grikscheit T, Wang K, Upperman JS, Ford HR. Pediatric Surgery. In: Brunicardi F, Andersen DK, Billiar TR, Dunn DL, Hunter JG, Matthews JB, Pollock RE. eds. Schwartz’s Principles of Surgery, 10e New York, NY: McGraw-Hill; 2015

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