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. 1998 Oct;43(4):542–547. doi: 10.1136/gut.43.4.542

Oncological implications of RET gene mutations in Hirschsprung's disease

R Sijmons 1, R Hofstra 1, F Wijburg 1, T Links 1, R Zwierstra 1, A Vermey 1, D Aronson 1, G Tan-Sindhunata 1, G Brouwers-Smalbraa 1, S Maas 1, C Buys 1
PMCID: PMC1727297  PMID: 9824583

Abstract

Background—Germline mutations of the RET proto-oncogene identical to those found in the tumour predisposition syndrome multiple endocrine neoplasia type 2A (MEN2A), were detected in 2.5-5% of sporadic and familial cases of Hirschsprung's disease. Some patients with Hirschsprung's disease may therefore be exposed to a highly increased risk of tumours. 
Aims—To define clinical use of RET gene testing in Hirschsprung's disease and related patient management from an oncological point of view. 
Methods—Sixty patients with Hirschsprung's disease were screened for RET mutations. In three, MEN2A type RET mutations were detected. Case reports for these three patients are presented. 
Results and conclusions—Only 22 families or sporadic patients with Hirschsprung's disease and MEN2A type RET mutations have been reported. Therefore, it is difficult to predict tumour risk for patients with familial or sporadic Hirschsprung's disease, and their relatives, who carry these mutations. For these mutation carriers, periodic screening for tumours as in MEN2A is advised, but prophylactic thyroidectomy is offered hesitantly. RET gene testing in familial or sporadic Hirschsprung's disease is not recommended at present outside a complete clinical research setting. In combined MEN2A/Hirschsprung's disease families RET gene testing, tumour screening, and prophylactic thyroidectomy are indicated as in MEN2A. 



Keywords: DNA analysis; Hirschsprung's disease; multiple endocrine neoplasia type 2A; RET

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Figure 1 .

Figure 1

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Pedigrees of the families of the index patients. In (A) patient 1 is indicated with an arrow. In (B) patient 2 is indicated with an arrow; she probably has combined MEN2A/HD. Her relatives could not be tested for the RET mutation or screened for MEN 2 tumours. Numbers within squares represent the additional number of asymptomatic males in that generation. In (C) patient 3 is indicated with an arrow; the mutation was not shown in his parents. HD, Hirschsprung's disease. 


Selected References

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