Variants of Hirschsprung Disease
Variants of Hirschsprung disease (HD) are a group of conditions that clinically resemble HD despite the presence of ganglion cells in rectal suction biopsies. The characterization and differentiation of various entities is mainly based on histological and immunohistochemical findings of biopsies from patients with functional intestinal obstruction.
Over the last decades, several groups have focused on the investigation and definition of variant HD such as intestinal neuronal dysplasia, isolated hyperganglionosis, internal anal sphincter achalasia, immature ganglia, and smooth muscle cell disorders such as megacystis microcolon intestinal hypoperistalsis syndrome. However, definition of the above-mentioned entities remains a controversial issue and research is ongoing to standardize diagnostic criteria, specific therapy, and outcome criteria.
This chapter summarizes the current knowledge of the above-mentioned entities of variant HD.
KeywordsHirschsprung’s disease Intestinal neuronal dysplasia Hypoganglionosis Internal sphincter achalasia Megacystis microcolon intestinal hypoperistalsis syndrome
- Friedmacher F, Puri P. Comparison of posterior internal anal sphincter myectomy and intrasphincteric botulinum toxin injection for treatment of internal anal sphincter achalasia: a meta-analysis. Pediatr Surg Int. 2012;28:765–71. https://doi.org/10.1007/s00383-012-3123-5.CrossRefPubMedGoogle Scholar
- Garel C, Dreux S, Philippe-Chomette P, et al. Contribution of fetal magnetic resonance imaging and amniotic fluid digestive enzyme assays to the evaluation of gastrointestinal tract abnormalities. Ultrasound Obstet Gynecol. 2006;28:282–91. https://doi.org/10.1002/uog.2799.CrossRefPubMedGoogle Scholar
- Halim D, Wilson MP, Oliver D, Brosens E, Verheij JB, Han Y, et al. Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice. Proc Natl Acad Sci U S A. 2017b;114(13):E2739–47.PubMedPubMedCentralCrossRefGoogle Scholar
- Martucciello G, Pini Prato A, Puri P, et al. Controversies concerning diagnostic guidelines for anomalies of the enteric nervous system: a report from the fourth international symposium on Hirschsprung’s disease and related neurocristopathies. In: 2005 edn. 2005. p 1527–31.Google Scholar
- Piotrowska AP, Solari V, Puri P. Distribution of interstitial cells of Cajal in the internal anal sphincter of patients with internal anal sphincter achalasia and Hirschsprung disease. Arch Pathol Lab Med. 2003;127:1192–5. https://doi.org/10.1043/1543-2165(2003)127<1192:DOICOC>2.0.CO;2.CrossRefPubMedGoogle Scholar
- Tuzovic L, Tang S, Miller RS, Rohena L, Shahmirzadi L, Gonzalez K, et al. New insights into the genetics of fetal megacystis: ACTG2 mutations, encoding gamma-2 smooth muscle actin in megacystis microcolon intestinal hypoperistalsis syndrome (Berdon Syndrome). Fetal Diagn Ther. 2015;38(4):296–306.PubMedCrossRefGoogle Scholar
- Wangler MF, Gonzaga-Jauregui C, Gambin T, Penney S, Moss T, Chopra A, et al. Heterozygous de novo and inherited mutations in the smooth muscle actin (ACTG2) gene underlie megacystis-microcolon-intestinal hypoperistalsis syndrome. PLoS Genet. 2014;10(3):e1004258.PubMedPubMedCentralCrossRefGoogle Scholar