Background-Germline mutations of the RET proto-oncogene identical to t
hose found in the tumour predisposition syndrome multiple endocrine ne
oplasia type 2A (MEN2A), were detected in 2.5-5% of sporadic and famil
ial cases of Hirschsprung's disease. Some patients with Hirschsprung's
disease may therefore be exposed to a highly increased risk of tumour
s. Aims-To define clinical use of RET gene testing in Hirschsprung's d
isease and related patient management from an oncological paint of vie
w. Methods-Sixty patients with Hirschsprung's disease were screened fo
r RET mutations. In three, MEN2A type RET mutations were detected. Cas
e reports for these three patients are presented. Results and conclusi
ons-Only 22 families or sporadic patients with Hirschsprung's disease
and MEN2A type RET mutations have been reported. Therefore, it is diff
icult to predict tumour risk for patients with familial or sporadic Hi
rschsprung's disease, and their relatives, wine carry these mutations,
For these mutation carriers, periodic screening for tumours as in MEN
2A is advised, but prophylactic thyroidectomy is offered hesitantly. R
ET gene testing in familial or sporadic Hirschsprung's disease is not
recommended at present outside a complete clinical research setting. I
n combined MEN2A/Hirschsprung's disease families RET genre testing, tu
mour screening, and prophylactic thyroidectomy are indicated as in MEN
2A.