C634Y mutation in RET-induced multiple endocrine neoplasia type 2A: A case report

Abstract

BACKGROUND

Multiple endocrine neoplasia type 2 (MEN2) is a rare, autosomal dominant endocrine disease. Currently, the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis. Once an RET carrier is detected, family members should be screened to enable early detection of medullary thyroid carcinoma, pheochromocytoma, and hyperparatitity. Among these, medullary thyroid carcinoma is the main factor responsible for patient mortality. Accordingly, delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners.

CASE SUMMARY

Herein, we present RET proto-oncogene mutations, clinical characteristics, and treatment strategies in a family with MEN2A. A family study was conducted on patients diagnosed with MEN2A. DNA was extracted from the peripheral blood of family members, and first-generation exon sequencing of the RET proto-oncogene was conducted. The C634Y mutation was identified in three family members spanning three generations. Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas. A 9-year-old child harboring the gene mutation was diagnosed with medullary thyroid carcinoma. Surgical resection of the tumors was performed. All family members were advised to undergo complete genetic testing related to the C634Y mutation, and the corresponding treatments administered based on test results and associated clinical guidelines.

CONCLUSION

Advancements in MEN2A research are important for familial management, assessment of medullary thyroid cancer invasive risk, and deciding surgical timing.

Keywords: Multiple endocrine neoplasia type 2A; Mutation; RET proto-oncogene; Medullary thyroid carcinoma; Pheochromocytoma; Case report

Core Tip: Gene sequencing was performed on an adult Asian female patient with bilateral pheochromocytoma and thyroid carcinoma. A mutation, characterized by a nucleotide (c.T1901A) and amino acid (p.Cys634Tyr) change, was identified, supporting multiple endocrine neoplasia type 2A development. Genetic screening of family members revealed the patient’s father and son are carriers of the mutation. Clinical follow-up direction and treatment plan were guided by genetic testing. The patient and her son were diagnosed with orthotopic medullary thyroid carcinoma, facilitating timely and early detection in the early stage of cancer and potentially improving the survival rate of patients.