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Association of multiple endocrine neoplasia type 2 and Hirschsprung disease
Author(s) -
Giovanni Romeo,
Isabella Ceccherini,
J. Celli,
Manuela Priolo,
Nicola Betsos,
Giulia Bonardi,
Marco Seri,
Ling Yin,
Margherita Lerone,
Vincenzo Jasonni,
G. Martucciello
Publication year - 1998
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1046/j.1365-2796.1998.00332.x
Subject(s) - medicine , missense mutation , multiple endocrine neoplasia type 2 , mutation , germline mutation , gastroenterology , phenotype , ret proto oncogene , medullary carcinoma , disease , multiple endocrine neoplasia , pathology , thyroid , genetics , thyroid carcinoma , gene , biology
Romeo G, Ceccherini I, Celli J, Priolo M, Betsos N, Bonardi G, Seri M, Yin L, Lerone M, Jasonni V, Martucciello G (University of Genoa Medical School, Genoa, Italy; International Agency for Research on Cancer, Lyon, France). Association of multiple endocrine neoplasia type 2 and Hirschsprung disease (Minisymposium: MEN & VHL). J Intern Med 1998; 243 : 515–20. 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.