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Hirschsprung disease

Nature Reviews Disease Primers volume 9, Article number: 54 (2023) Cite this article

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Abstract

Hirschsprung disease (HSCR) is a rare congenital intestinal disease that occurs in 1 in 5,000 live births. HSCR is characterized by the absence of ganglion cells in the myenteric and submucosal plexuses of the intestine. Most patients present during the neonatal period with the first meconium passage delayed beyond 24 h, abdominal distension and vomiting. Syndromes associated with HSCR include trisomy 21, Mowat–Wilson syndrome, congenital central hypoventilation syndrome, Shah–Waardenburg syndrome and cartilage–hair hypoplasia. Multiple putative genes are involved in familial and isolated HSCR, of which the most common are the RET proto-oncogene and EDNRB. Diagnosis consists of visualization of a transition zone on contrast enema and confirmation via rectal biopsy. HSCR is typically managed by surgical removal of the aganglionic bowel and reconstruction of the intestinal tract by connecting the normally innervated bowel down to the anus while preserving normal sphincter function. Several procedures, namely Swenson, Soave and Duhamel procedures, can be undertaken and may include a laparoscopically assisted approach. Short-term and long-term comorbidities include persistent obstructive symptoms, enterocolitis and soiling. Continued research and innovation to better understand disease mechanisms holds promise for developing novel techniques for diagnosis and therapy, and improving outcomes in patients.

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Fig. 1: Clinical and radiological diagnosis of Hirschsprung disease.
Fig. 2: Timeline of key advances in the history of Hirschsprung disease.
Fig. 3: Pathophysiology and signalling pathways in Hirschsprung disease.
Fig. 4: Anorectal anatomy, rectal biopsy and histopathological diagnosis of Hirschsprung disease.
Fig. 5: Different surgical techniques for pull-through.
Fig. 6: Algorithm for the management of persistent obstructive symptoms and soiling.
Fig. 7: Optimizing functional outcomes and quality of life after pull-through in Hirschsprung disease.

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Acknowledgements

L.S.C. is supported by grants from the National Institutes of Health (K08DK133673), the American College of Surgeons, and the American Pediatric Surgical Association. A.G. supported by grants (R01DK125047 and R21AI163503) from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Paediatric Surgery, Robert-Debré Children’s University Hospital, Paris, France

    Louise Montalva & Arnaud Bonnard

  2. Faculty of Health, Paris-Cité University, Paris, France

    Louise Montalva & Arnaud Bonnard

  3. NeuroDiderot, INSERM UMR1141, Paris, France

    Louise Montalva & Arnaud Bonnard

  4. Division of Paediatric Surgery, Texas Children’s Hospital, Houston, TX, USA

    Lily S. Cheng

  5. Division of Paediatric Surgery, University of Virginia, Charlottesville, VA, USA

    Lily S. Cheng

  6. Department of Pathology, Seattle Children’s Hospital, Seattle, WA, USA

    Raj Kapur

  7. Division of Paediatric Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada

    Jacob C. Langer

  8. Department of Pathology, Robert-Debré and Necker Children’s University Hospital, Paris, France

    Dominique Berrebi

  9. Department of Paediatric Surgery, Helsinki University Central Hospital, Helsinki, Finland

    Kristiina Kyrklund & Mikko Pakarinen

  10. Department of Surgery, Division of Paediatric Surgery, Radboudumc-Amalia Children’s Hospital, Nijmegen, Netherlands

    Ivo de Blaauw

  11. Department of Paediatric Surgery, Children’s Hospital Colorado, Aurora, CO, USA

    Ankush Gosain

Authors
  1. Louise Montalva
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  2. Lily S. Cheng
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  3. Raj Kapur
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Contributions

Introduction (L.M. and A.G.); Epidemiology (K.K. and I.de B.); Mechanisms/pathophysiology (L.S.C., L.M. and I.de B.); Diagnosis (R.K., D.B. and L.M.); Management (A.B., L.S.C., J.C.L., L.M. and A.G.); Quality of life (M.P. and K.K.); Outlook (L.S.C. and A.G.); Overview of the Primer (L.M. and A.G.).

Corresponding authors

Correspondence to Louise Montalva or Ankush Gosain.

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Nature Reviews Disease Primers thanks A. Burns, R. Hotta, P. Tam, T. Wester and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Montalva, L., Cheng, L.S., Kapur, R. et al. Hirschsprung disease. Nat Rev Dis Primers 9, 54 (2023). https://doi.org/10.1038/s41572-023-00465-y

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