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Paraganglioma, neuroblastoma, and a SDHB mutation: Resolution of a 30‐year‐old mystery
Author(s) -
Schimke R. Neil,
Collins Debra L.,
Stolle Catherine A.
Publication year - 2010
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.33384
Subject(s) - sdhb , paraganglioma , pheochromocytoma , neuroblastoma , renal cell carcinoma , mutation , gene , biology , population , cancer research , genetics , medicine , germline mutation , pathology , endocrinology , environmental health , cell culture
Familial paraganglioma/pheochromocytoma (PGL/PCC) is genetically heterogenous with mutations in three of the four subunits of the heterotetrameric mitochondrial complex II enzyme succinate dehydrogenase (SDH) being causally responsible for the majority of cases. In addition to PGL/PCC an array of non‐paraganglial tumors have been described in affected individuals. We present a 30‐year follow‐up on the family of a deceased patient who synchronously developed malignant neuroblastoma (NBL), PCC, and renal cell carcinoma (RCC). Other family members with late onset disease have come to our attention, and molecular study revealed a mutation in the SDHB gene. Despite the embryologic relationship, NBL has been seen in only two previous patients with familial PGL/PCC, both with deletions of the SDHB gene. Review of the literature suggests the lack of a reported association between NBL and familial PGL/PCC may be an ascertainment bias. We further suggest that study of the SDH genes in NBL survivors who develop secondary solid tumors, particularly RCC, may correct this bias, and provide for more effective and comprehensive tumor screening in this patient population. © 2010 Wiley‐Liss, Inc.