陆军军医大学学报 (Feb 2024)
Hereditary pheochromocytoma/paraganglioma and associated syndromes: a clinical and genetic study
Abstract
Objective To summarize and analyze the clinical phenotypes, hereditary features and treatment and follow-up strategies of different hereditary pheochromocytoma/paragangliomas (PCC/PGL) and related syndromes. Methods Forty-four clinically diagnosed PCC/PGL patients admitted in our hospital from January 2000 to August 2022 were enrolled, and the clinical data of them and their family members were collected.Second-generation sequencing was performed on 43 patients for genetic detection, and Sanger sequencing was applied to verify the mutation of the probands and family members. Results There were 15 patients diagnosed with hereditary PCC/PGL, including 7 cases of von Hippel-Lindau (VHL) syndrome, 3 cases of multiple endocrine neoplasia type 2(MEN2), and 5 cases of familial paraganglioma syndrome.Seven VHL syndrome families were diagnosed as VHL2A (c.500G>A), VHL2B (c.239G>T and c.444_457del), and VHL2C (c.293A>G) according to their clinical manifestations.All probands received surgical treatment, and 2 cases of recurrent PCC and the patients with multiple renal cancer also received targeted therapy with sunitinib.Three MEN2 families carried c.1901G>C, c.1832G>A, and c.1901G>A missense mutations, respectively, and were diagnosed with MEN2A clinically.All of them underwent adrenalectomy and thyroidectomy, including one for preventive thyroidectomy.Among the 5 familial paraganglioma syndrome families, 4 patients carried SDHB mutations (SDHB: c.343C>T, c.541-2A>G, c.575G>A, c.268C>T) and 1 patient carried an SDHD mutation (SDHD: c.337_340del).Sporadic retroperitoneal PGL were most common. Conclusion More than 1/3 of PCC/PGL patients carry germline gene mutations, showing obvious genotype-phenotype correlation.Genetic diagnosis technology plays an important guidance role for clinical precision treatment and follow-up, and genetic counseling.
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