Two Cases of Hereditary Paraganglioma-Pheochromocytoma Syndrome in Siblings, Caused by a Novel Succinate Dehydrogenase Complex Subunit D Variant

两例由新型琥珀酸脱氢酶复合物亚基D变异引起的遗传性副神经节瘤-嗜铬细胞瘤综合征(同胞发生)

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Abstract

INTRODUCTION: Pheochromocytomas and paragangliomas are increasingly recognized as hereditary malignancies, with ~30%-40% of cases involving germline variants. We report a familial case of hereditary pheochromocytoma-paraganglioma syndrome caused by a novel variant in the SDHD gene. CASE PRESENTATION: An 11-year-old boy was diagnosed with retroperitoneal paraganglioma. Pathological analysis confirmed the resected tumor as a pheochromocytoma and paraganglioma. SDHD sequencing from blood and tumor tissues revealed a c.74dupT single-nucleotide insertion variant, which was absent from all public databases. Another surgery was performed eight years later because of enlargement of the retroperitoneal mass and elevated plasma norepinephrine levels. His 17-year-old sister was later diagnosed with bilateral adrenal pheochromocytomas. Pathological analysis confirmed the resected tumors as pheochromocytoma and paraganglioma. She harbored the same genetic variant inherited from the children's asymptomatic father. CONCLUSION: Early identification of hereditary risks associated with pheochromocytomas and paragangliomas facilitates appropriate lifelong surveillance, timely treatment decisions, and informed genetic counseling.

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