Oncological implications of RET gene mutations in Hirschsprung's disease.
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.


OBJECTIVE
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.


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.
Sijmons
R H
RH
Department of Medical Genetics, University of Groningen, The Netherlands.
Hofstra
R M
RM
Wijburg
F A
FA
Links
T P
TP
Zwierstra
R P
RP
Vermey
A
A
Aronson
D C
DC
Tan-Sindhunata
G
G
Brouwers-Smalbraak
G J
GJ
Maas
S M
SM
Buys
C H
CH
D000328:Adult; D002675:Child, Preschool; D029721:Drosophila Proteins; D005260:Female; D018095:Germ-Line Mutation; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D010375:Pedigree; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila