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

Background/Purpose: Germline mutations of the RET-mediated or SOX10-mediate d 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 w ere studied, DNA sequences of all the RET/GDNF/NTN and SOX10 coding regions were determined by the direct DyeDeoxy Terminator Cycle method. Data on th e patients' clinical courses were obtained retrospectively from their medic al charts and surgical records. Results: RET or SOX10 germline mutations were identified in 11 of the 16 pa tients (68.8%). In children with aganglionosis up to the jejunum or ileum, most grew up within normal ranges, and the frequency of bowel movements dec reased to 2 to 4 times per day within 5 years. However, in 5 infants with t otal intestinal aganglionosis, only 2 survived beyond 2 years of age, both of whom underwent Ziegler's myectomy-myotomy. A SOX10 mutation was identifi ed 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 su rgical results in this series of TCA patients, whereas the mutational analy sis suggested 2 disease categories of TCA showing different postoperative c ourses, which may reflect the disparate pathogenesis in the enteric nervous system development induced by impaired RET or SOX10 signaling pathway. J P ediatr Surg 36:1685-1688. Copyright (C) 2001 by W.B Saunders Company.