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The risk of medullary thyroid carcinoma in patients with Hirschsprung's disease

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Abstract

Hirschsprung's disease (HD) can be associated with the development of neuroendocrine tumours such as medullary thyroid carcinoma (MTC). The RET proto-oncogene is the major gene responsible for both HD and MTC. Mutations in exon 10 (codons 609, 611, 618, 620) were found in patients with co-occurrence of HD and MTC. The aim of the study was to screen the MTC risk in patients with HD. The prospective and retrospective genetic analyses comprised 56 HD patients (41 males, 15 females, aged 0–47). The prospective subgroup of patients consisted of 34 patients (25 boys, 9 girls) operated on between June 2003 and December 2005. The retrospective subgroup comprised 22 patients (16 boys, 6 girls) of 194 patients who were operated on between December 1979 and May 2003, non-systematically chosen preferably for total colonic aganglionosis (TCA). DNAs were isolated from blood and resected segments of aganglionic bowel. The HD patients and nine available family members (2 HD) were tested for RET mutations in exons 10, 11, 13, 14, 15 and 16. Direct double-stranded fluorescent sequencing revealed typical germline heterozygous MTC risk RET mutations in 3/56 (5.4%) female HD patients: Cys609Tyr, Cys620Arg (both exon 10) and Tyr791Phe (exon 13). Two of these patients had TCA and one patient had classical type of HD. One TCA patient developed clinical stage of MTC and underwent total thyroidectomy (TTE). The other two RET positive HD patients (aged 7 and 25 years) are screened for calcitonin level and they are without TTE till now. Two family members (mothers of TCA patients) with detected RET mutation underwent prophylactic TTE with MTC finding. Results showed the benefit of systematic RET mutation screening in HD patients in order to identify the risk of MTC in preclinical stage of the disease in patients with HD and their family members. We recommend to investigate not only exon 10 but also exon 13.

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Abbreviations

MTC:

Medullary, thyroid carcinoma

HD:

Hirschsprung's disease

RET:

Rearranged during transfection

TCA:

Total colonic aganglionosis

TTE:

Total thyroidectomy

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Acknowledgments

We would like to thank all the subjects who participated in this study. This work was supported by IGA MH CR NR/7806-3 and GACR 301/06/P425. The Family 1 with Cys609Tyr mutation was published previously as a case report in the article of Dvořáková et al. [12].

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Authors and Affiliations

  1. Department of Pediatric Surgery of the 2nd Faculty of Medicine, Charles University and Hospital Prague—Motol, V Úvalu 84, 150 06, Prague, Czech Republic

    Richard Škába

  2. Department of Molecular Endocrinology, Institute of Endocrinology, Prague, Czech Republic

    Šárka Dvořáková, Eliška Václavíková & Běla Bendlová

  3. Department of Nuclear Medicine and Endocrinology of the 2nd Faculty of Medicine, Charles University and Hospital Prague—Motol, Prague, Czech Republic

    Petr Vlček

  4. Department of Pathology and Molecular Medicine of the 2nd Faculty of Medicine, Charles University and Hospital Prague—Motol, Prague, Czech Republic

    Miroslava Frantlová

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  1. Richard Škába
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  2. Šárka Dvořáková
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  3. Eliška Václavíková
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  4. Petr Vlček
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  5. Miroslava Frantlová
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  6. Běla Bendlová
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Correspondence to Richard Škába.

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Škába, R., Dvořáková, Š., Václavíková, E. et al. The risk of medullary thyroid carcinoma in patients with Hirschsprung's disease. Pediatr Surg Int 22, 991–995 (2006). https://doi.org/10.1007/s00383-006-1785-6

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