Association of multiple endocrine neoplasia type 2 and Hirschsprung disease

G. Romeo, I. Ceccherini, J. Celli, M. Priolo, N. Betsos, G. Bonardi, M. Seri, L. Yin, M. Lerone, V. Jasonni, G. Martucciello

Research output: Contribution to journalArticlepeer-review


In a few patients with Hirschsprung disease (HSCR) and no clinical symptoms of multiple endocrine neoplasia type 2 (MEN-2A) or medullary thyroid carcinoma (MTC), missense mutations in the cysteine residues 609 and 620 of the Ret gene have been identified. In several pedigrees with either MEN-2A or familial MTC (FMTC) a documented germline mutation in cysteine 618 or 620 follows the segregation of the disease phenotype. The appearance of the HSCR phenotype in such patients and pedigrees cannot be easily reconciled with the gain of function which is associated with the dominant oncogenic effect of MEN-2A mutations. Gastrointestinal manifestations are known to occur also in association with MEN-2B but, to the best of our knowledge, in only very few cases the intestinal phenotype of MEN-2B has been investigated by enzymo- histochemical techniques, as in the present work. We report an extensive molecular study of patients, two with HSCR and FMTC carrying a Cys620Arg or Ser mutation and two with MEN-2B and gastrointestinal symptoms carrying a Met918Thr mutation. One of the latter two patients showed aganglionosis of the last 5 cm of rectum which caused a congenital megacolon leading to the diagnosis and operation for HSCR. The mutation screening of all the exons of Ret in 3 of these patients did not reveal any additional mutation. Therefore these results do not support the hypothesis of additional constitutional Ret mutations in patients showing association of MEN-2 and HSCR, whilst the histochemical and clinical data in one of these patients indicate that MEN- 2B can be associated with a true form of short segment HSCR.

Original languageEnglish
Pages (from-to)515-520
Number of pages6
JournalJournal of Internal Medicine
Issue number6
Publication statusPublished - 1998


  • Associated phenotypes
  • Hirschsprung disease (HSCR)
  • Multiple endocrine neoplasia type 2 (MEN-2)
  • Ret mutations

ASJC Scopus subject areas

  • Internal Medicine


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