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Genetic testing for multiple endocrine neoplasia type 2 (MEN2) / familial medullary thyroid cancer (FMTC) (R218)

Background information

Multiple endocrine neoplasia (MEN) describes a dominant familial predisposition to tumours of endocrine organs.

MEN2 and MEN3 (or MEN2A and MEN2B) (OMIM 171400 and 162300) are characterised by medullary thyroid carcinoma (MTC), pheochromocytoma (PCC) and hyperparathyroidism, with MEN3 (MEN2B) also associated with ganglioneuromas of the lips, tongue and colon, and a marfanoid habitus.

Penetrance is age-related but 95% MEN2A and 100% MEN2B (MEN3) patients will develop MTC in their lifetime.

FMTC (OMIM 155240) is the autosomal dominant inheritance of predisposition to MTC with no extra-thyroid manifestations of multiple endocrine neoplasia.

About 75% of medullary thyroid carcinoma is sporadic; these cases are unilateral. Bilateral multifocal medullary carcinoma is a key feature of MEN2A.

Testing strategy

Clinically affected probands:

R218.1 - targeted analysis for small variants in exons 5, 8, 10, 11, 13, 14, 15 and 16 of the RET gene

Targeted analysis for known / previously reported familial variants:

Diagnostic confirmation in individuals at risk of inheriting a previously reported familial pathogenic variant and clinically suspected of having the familial condition (R240)
Testing in clinically unaffected family members at risk of inheriting a previously reported familial pathogenic variant (R242)
Segregation studies in affected family members to aid variant interpretation (R375)
Prenatal diagnosis is not typically requested