RET Lys666Asn has low MEN2-related tumours penetrance but may be associated with pheochromocytoma

#4465

Introduction: Multiple Endocrine Neoplasia type 2 (MEN2) is caused by germline pathogenic variants (PVs) in the RET proto-oncogene, leading to medullary thyroid carcinoma (MTC), pheochromocytoma, and primary hyperparathyroidism (PHPT). RET c.1998G>C, p.Lys666Asn is a rare PV, with 33 cases described thus far, and is associated with low penetrance of MEN2-related tumours, but its clinical significance remains incompletely understood.

Aim(s): To expand the clinical understanding of the RET Lys666Asn variant.

Materials and methods: Index patients carrying the RET Lys666Asn variant were identified through clinical genetic testing in two referral medical centres. Comprehensive clinical evaluation, biochemical screening, and imaging studies were performed to assess the presence of MTC, pheochromocytoma, and PHPT of the index patients and family members carrying the Lys666Asn variant. We conducted a literature search on additional Lys666Asn carriers and their clinical manifestations.

Conference:

Presenting Author: Halperin R

Authors: Halperin R, Peshes-Yaloz N, Tirosh A, Twito O,

Keywords: MEN2, pheochromocytoma, hyperparathyroidism, medullary thyroid carcinoma,