Hirschsprung’s Disease: Pathogenesis and Overview

  • Hisayoshi Kawahara


Surgical options using various techniques of pull-through surgery have been performed in clinical practice as a consensus therapy for years, whereas the pathogenesis of Hirschsprung’s disease (HD) remains unclear. Among all of patients with HD, only 20% of cases were familial, and the majority of cases were sporadic with the normal genes associated with the enteric nervous system (ENS). The remaining 80% of sporadic cases highlights the need to understand the etiology and pathogenic mechanism of HD. There are two major theories that explain the pathogenesis of HD in children. One is nongenetic pathogeneses and the other is genetic. The nongenetic factors include the abnormalities in migration of neural crest cells (NCCs), microenvironment surrounding the NCCs, cell adhesion molecules, neurotrophic factors, immunologic response in utero, epithelial-derived signal, and autophagy. These abnormalities may be responsible for the innervation deficiency due to incomplete colonization of enteric NCCs in the gut. The other theory responsible for the pathogenesis of HD is the variety of gene mutations including ret. proto-oncogene (RET), glial cell-derived neurotrophic factor (GDNF), endothelin receptor B (EDNRB), sex-determining region Y-box 10 (SOX10), and so on. In this chapter, the pathogeneses of HD are overviewed based on literatures.


Enteric nervous system Neural crest cell Migration Microenvironment Gene Ret proto-oncogene (RET


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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Hisayoshi Kawahara
    • 1
  1. 1.Department of Pediatric SurgeryHamamatsu University School of MedicineHamamatsuJapan

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