To screen the RET gene mutation in a pedigree of multiple endocrine neoplasia type 2A (MEN2A).

Clinical data of 21 members in a MEN2A family were collected from June 1976 to February 2013. Systemic clinical investigations including biochemical testing, imaging examinations and germline RET screening were performed.

RET screening showed heterozygous missense mutations of cysteine to tyrosine at codon 634 on exon 11 in 10 MEN2A patients (p.C634Y, 10/21) including 8 males and 2 females, which were completely consistent with the clinical manifestations. There were 7 patients with medullary thyroid carcinoma (MTC), including one with concurrent papillary thyroid carcinoma. The mean age at onset was 34.3 years (range: 21-55), and the mean maximum diameter of MTC was 2.8 cm (range: 0.8-3.7). Five patients underwent non-normative thyroidectomy, 2 patients underwent total thyroidectomy with modified bilateral neck dissection. The mean follow-up period for MTC was 172.4 months (range: 10-440), elevating calcitonin level was found in 4 patients, normal calcitonin level in 3 of the 7 patients, 3 were combined with bilateral pheochromocytoma (2 synchronous and 1 metachronous), the mean age at onset was 48.3 years (range: 42-58), the maximum diameter of pheochromocytoma was 7.0 cm (range: 4.4-8.5). All 3 patients underwent bilateral (2 synchronous, 1 metachronous) cortical-sparing adrenalectomy, none of whom needed long-term steroid replacement and developed Addisonian crisis during the observation period (followed for 15, 17 and 120 months, respectively). Three asymptomatic carriers with a mean age of 11.7 (range: 8-15), rejected surgery and were closely monitored (followed for up to 17 months). The carries had a slightly elevated calcitonin and 1 presented bilateral thyroid minimal lesions (0.2 cm).

Screening of RET-mutation in MEN2A pedigree is helpful for early diagnosis, normative treatment, reducing complications and improve the long-term outcome of MEN2A.

Multiple endocrine neoplasia type 2a; Carcinoma, medullary; Thyroid gland; Pheochromocytoma, adrenal glands; Proto-oncogene, RET