Relationship between the type of RET/GDNF/NTN or SOX10 gene mutations and long-term results after surgery for total colonic aganglionosis with small bowel involvement

J Pediatr Surg. 2001 Nov;36(11):1685-8. doi: 10.1053/jpsu.2001.27960.


Background/purpose: Germline mutations of the RET-mediated or SOX10-mediated signaling pathway genes have been reported in total colonic aganglionosis (TCA). The authors investigated the possible relationship between the type of such genomic abnormalities and surgical outcomes.

Methods: Sixteen patients with TCA with extensive small bowel involvement were studied. DNA sequences of all the RET/GDNF/NTN and SOX10 coding regions were determined by the direct DyeDeoxy Terminator Cycle method. Data on the patients' clinical courses were obtained retrospectively from their medical charts and surgical records.

Results: RET or SOX10 germline mutations were identified in 11 of the 16 patients (68.8%). In children with aganglionosis up to the jejunum or ileum, most grew up within normal ranges, and the frequency of bowel movements decreased to 2 to 4 times per day within 5 years. However, in 5 infants with total intestinal aganglionosis, only 2 survived beyond 2 years of age, both of whom underwent Ziegler's myectomy-myotomy. A SOX10 mutation was identified in an infant with Shah-Waardenburg's syndrome, and he showed persistent bowel malfunction.

Conclusion: The existence or type of RET mutation usually did not affect surgical results in this series of TCA patients, whereas the mutational analysis suggested 2 disease categories of TCA showing different postoperative courses, which may reflect the disparate pathogenesis in the enteric nervous system development induced by impaired RET or SOX10 signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Body Height
  • Body Weight
  • Child, Preschool
  • DNA-Binding Proteins / genetics*
  • Female
  • Follow-Up Studies
  • Germ-Line Mutation / genetics*
  • Glial Cell Line-Derived Neurotrophic Factor
  • High Mobility Group Proteins / genetics*
  • Hirschsprung Disease / genetics*
  • Hirschsprung Disease / surgery*
  • Humans
  • Infant
  • Male
  • Nerve Growth Factors*
  • Nerve Tissue Proteins / genetics*
  • SOXE Transcription Factors
  • Transcription Factors
  • Treatment Outcome


  • DNA-Binding Proteins
  • GDNF protein, human
  • Glial Cell Line-Derived Neurotrophic Factor
  • High Mobility Group Proteins
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • SOX10 protein, human
  • SOXE Transcription Factors
  • Transcription Factors