RET (C620R) Mutation in a Hirschsprung Disease Family: A Case Report Unveiling Asymptomatic Pheochromocytoma and Unmanifested Medullary Thyroid Carcinoma.

gene variants have been reported in a proportion of patients with familial Hirschsprung disease (F-HSCR), and certain variants are also associated with hereditary medullary thyroid carcinoma (MTC). Clinical guidelines have been developed to support decision-making regarding the timing of prophylactic surgery based on individual risk stratification. These recommendations emphasize the importance of tailoring the timing of thyroidectomy to the specific risk category assigned to each genetic variant, with the goal of preventing disease progression while minimizing unnecessary intervention. We encountered a case of F-HSCR associated with the germline c.1858T>C (p.C620R) activating variant in exon 10, which is known to confer moderate risk for MTC. Although only a limited number of MTC cases have been reported in the context of Hirschsprung disease (HD), and it remains unclear whether the management should align with that of MEN2A, we initiated surveillance for MTC in this family. No elevation of key markers, including carcinoembryonic antigen (CEA) or calcitonin, was observed, and no cases of MTC were detected across generations. However, a pheochromocytoma (PHEO) was diagnosed in one family member through screening for plasma-free metanephrines (fMNs). We present our findings in this family and provide a review of relevant literature.