Hereditary Bilateral Synchronous Pheochromocytomas in a Tibetan Pedigree With a Germline Adenomatous Polyposis Coli (APC) Mutation

Abstract

Background: Germline pathogenic mutations associated with pheochromocytoma (PHEO) are present in most patients with hereditary bilateral PHEOs. Adenomatous polyposis coli (APC) gene has previously been identified as a tumor suppressor gene in familial adenomatous polyposis and colorectal cancers, but not PHEO. Methods: A father and a son from Tibet were clinically diagnosed with bilateral synchronous PHEOs. The son underwent staged retroperitoneal laparoscopic bilateral total adrenalectomy, and the father underwent retroperitoneal laparoscopic left adrenalectomy. A pedigree investigation was performed with a follow-up of 4 years. Whole-exome sequencing was performed to reveal the susceptibility genes in the pedigree. Results: The adrenal masses in the father and son were pathologically diagnosed as hereditary bilateral synchronous PHEOs. A pedigree investigation of 26 family members spanning 3 generations was performed. Multiple endocrine gland–related tumors, including PHEO, pancreatic neuroendocrine tumor, and pituitary adenoma, were diagnosed in the family. DNA sequencing identified a novel heterozygous germline missense mutation (c.896C>G) of the APC gene in the proband. The same heterozygous germline mutation of the APC gene was also present in the pedigree. Conclusions: We reported a pedigree from Tibet with hereditary bilateral synchronous PHEOs, which revealed a novel heterozygous germline missense mutation of the APC gene that may predispose to PHEO.