caa a22 4500 44533102X CHVBK 20180317142737.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s10689-011-9465-7 doi (NATIONALLICENCE)springer-10.1007/s10689-011-9465-7 Long-term outcomes, branch-specific expressivity, and disease-related mortality in von Hippel-Lindau type 2A [Elektronische Daten] [Sarah Nielsen, Wendy Rubinstein, Darcy Thull, Michaele Armstrong, Eleanor Feingold, Linwah Yip, Samuel Tisherman, Sally Carty] Although a large kindred with familial pheochromocytoma (Pheo) and paraganglioma (PGL) was discovered in 1962 and later found to represent von Hippel-Lindau (VHL) type 2A (mutation Y112H), the phenotype lacks current characterization. Branch-specific expressivity was suspected based on oral family history. Family pedigree analysis, prospective interviews, and extensive record review were used to extend the pedigree, determine phenotype, examine branch-specific expression, and analyze mortality rates over 5 decades. In its 3 known affected branches the kindred now comprises 107 people with or at-risk for VHL, of whom 49 have been diagnosed and 35/49 (71%) are clinically affected. Phenotypic cumulative lifetime risk was 71% for Pheo/PGL, 15% for hemangioblastoma, 33% for retinal angioma, 3% for renal cell carcinoma, and 3% for pancreatic cysts. The mean ages for VHL and Pheo/PGL diagnosis were younger in successive generations. Branch II-4 predominately expressed RA, while branch II-5 predominantly expressed Pheo/PGL. Disease-specific mortality occurred early and was less frequent in successive generations. This analysis of Y112H VHL confirms a high cumulative risk for pheochromocytoma/paraganglioma. Over time, both age at diagnosis and disease-specific mortality have decreased. The observed branch-specific expressivity prompts further study of genetic and environmental disease modifiers in this large family. Springer Science+Business Media B.V., 2011 Von Hippel-Lindau type 2A nationallicence Branch-specific expressivity nationallicence Pheochromocytoma nationallicence Hemangioblastoma nationallicence Retinal angioma nationallicence Renal cell carcinoma nationallicence Pheo : Pheochromocytoma nationallicence PGL : Paraganglioma nationallicence VHL : von Hippel-Lindau nationallicence RA : Retinal angioma nationallicence HB : Hemangioblastoma nationallicence RCC : Renal cell carcinoma nationallicence C : Pancreatic cyst nationallicence NET : Pancreatice neuroendocrine tumor nationallicence G : Generations nationallicence Nielsen Sarah Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, IL, USA aut Rubinstein Wendy NorthShore University HealthSystem, Evanston, IL, USA aut Thull Darcy Cancer Genetics Program, University of Pittsburgh Medical Center, Pittsburgh, PA, USA aut Armstrong Michaele Department of Surgery, Section of Endocrine Surgery, School of Medicine, University of Pittsburgh, 101 Kaufmann Building, 3471 Fifth Avenue, 15213, Pittsburgh, PA, USA aut Feingold Eleanor Department of Human Genetics, Graduate School of Public Health University of Pittsburgh, Pittsburgh, PA, USA aut Yip Linwah Department of Surgery, Section of Endocrine Surgery, School of Medicine, University of Pittsburgh, 101 Kaufmann Building, 3471 Fifth Avenue, 15213, Pittsburgh, PA, USA aut Tisherman Samuel Department of Surgery, Section of Endocrine Surgery, School of Medicine, University of Pittsburgh, 101 Kaufmann Building, 3471 Fifth Avenue, 15213, Pittsburgh, PA, USA aut Carty Sally Department of Surgery, Section of Endocrine Surgery, School of Medicine, University of Pittsburgh, 101 Kaufmann Building, 3471 Fifth Avenue, 15213, Pittsburgh, PA, USA aut Familial Cancer Springer Netherlands 10/4(2011-12-01), 701-707 1389-9600 10:4<701 2011 10 10689 https://doi.org/10.1007/s10689-011-9465-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10689-011-9465-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nielsen Sarah Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, IL, USA aut NATIONALLICENCE 700 1- Rubinstein Wendy NorthShore University HealthSystem, Evanston, IL, USA aut NATIONALLICENCE 700 1- Thull Darcy Cancer Genetics Program, University of Pittsburgh Medical Center, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Armstrong Michaele Department of Surgery, Section of Endocrine Surgery, School of Medicine, University of Pittsburgh, 101 Kaufmann Building, 3471 Fifth Avenue, 15213, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Feingold Eleanor Department of Human Genetics, Graduate School of Public Health University of Pittsburgh, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Yip Linwah Department of Surgery, Section of Endocrine Surgery, School of Medicine, University of Pittsburgh, 101 Kaufmann Building, 3471 Fifth Avenue, 15213, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Tisherman Samuel Department of Surgery, Section of Endocrine Surgery, School of Medicine, University of Pittsburgh, 101 Kaufmann Building, 3471 Fifth Avenue, 15213, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Carty Sally Department of Surgery, Section of Endocrine Surgery, School of Medicine, University of Pittsburgh, 101 Kaufmann Building, 3471 Fifth Avenue, 15213, Pittsburgh, PA, USA aut NATIONALLICENCE 773 0- Familial Cancer Springer Netherlands 10/4(2011-12-01), 701-707 1389-9600 10:4<701 2011 10 10689 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer