High penetrance of pheochromocytoma in multiple endocrine neoplasia 2 caused by germ line RET codon 634 mutation in Japanese patients.

OBJECTIVE

The precise penetrance of pheochromocytoma (PHEO) in multiple endocrine neoplasia type 2 (MEN2) has not been reported in a large cohort. In this study, we aimed to clarify the codon-specific penetrance of PHEO in MEN2.

DESIGN

We established a study group designated the 'MEN Consortium of Japan' in 2008 and asked physicians and surgeons to provide clinical and genetic information on patients they had treated up to 2011.

METHODS

Data were collected on patients identified as carriers of the RET mutation or diagnosed with medullary thyroid carcinoma (MTC) and/or PHEO with family history from 52 institutions all over Japan.

RESULTS

Of 493 registered MEN2 patients, RET mutation data were available for 390. Of these, 144 developed PHEOs, while 246 did not. The penetrance of PHEO was 25% by age 30 years, 52% by age 50 years, and 88% by age 77 years in RET mutation carriers with a codon 634 mutation. All patients with a codon 918 mutation (MEN2B) developed PHEO by age 56 years. Less than 32%penetrance of PHEO was seen in patients with mutations at codons other than 634 and 918.

CONCLUSIONS

Most patients with a codon 634 mutation develop PHEOs as well as MTC during their lifetime.