Genotype–phenotype correlation in von Hippel‐Lindau disease

• Published in: Acta ophthalmologica (Oxford, England) England), 2021-12, Vol.99 (8), p.e1492-e1500
• Main Authors: Reich, Michael, Jaegle, Sabine, Neumann‐Haefelin, Elke, Klingler, Jan‐Helge, Evers, Charlotte, Daniel, Moritz, Bucher, Felicitas, Ludwig, Franziska, Nuessle, Simone, Kopp, Julia, Boehringer, Daniel, Reinhard, Thomas, Lagrèze, Wolf A., Lange, Clemens, Agostini, Hansjuergen, Lang, Stefan J.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age; Aged; Aged, 80 and over; Central nervous system; Child; Clear cell-type renal cell carcinoma; DNA Mutational Analysis; Enucleation; Female; Fluorescein Angiography - methods; Follow-Up Studies; Fundus Oculi; Genetic Association Studies - methods; Genetic Predisposition to Disease; genotype –phenotype correlation; Genotypes; Germany - epidemiology; haemangioblastoma; Hemangioblastoma - diagnosis; Hemangioblastoma - epidemiology; Hemangioblastoma - etiology; Humans; Kidney cancer; Male; Medical prognosis; Middle Aged; Morbidity - trends; Mutation; Neuroendocrine tumors; Pancreatic carcinoma; Paraganglioma; Patients; Phenotypes; Pheochromocytoma; retina; Retina - diagnostic imaging; Retinal Neoplasms - diagnosis; Retinal Neoplasms - epidemiology; Retinal Neoplasms - etiology; Retrospective Studies; Tomography, Optical Coherence - methods; VHL; VHL protein; von Hippel-Lindau Disease - complications; von Hippel-Lindau Disease - epidemiology; von Hippel-Lindau Disease - genetics; Von Hippel-Lindau Tumor Suppressor Protein - genetics; Von Hippel-Lindau Tumor Suppressor Protein - metabolism; von Hippel‐Lindau disease; Young Adult
• ISSN: 1755-375X; 1755-3768
• DOI: 10.1111/aos.14843

Background/Aims Retinal haemangioblastomas (RH) remain a major cause of visual impairment in patients with von Hippel‐Lindau (VHL) disease. Identification of genotype–phenotype correlation is an important prerequisite for better management, treatment and prognosis. Methods Retrospective, single‐centre cohort study of 200 VHL patients. Genetic data and date of onset of RH, central nervous system haemangioblastomas (CNSH), pheochromocytoma/paraganglioma (PPGL), clear cell renal cell carcinoma (ccRCC) and pancreatic neuroendocrine neoplasm (PNEN) were collected. The number and locations of RH were recorded. Results The first clinical finding occurred at an age of 26 ± 14 years (y) [mean ± SD]. In 91 ± 3% (95% CI 88–94) of the patients, at least one RH occur until the age of 60y. A total of 42 different rare VHL gene variants in 166 patients were detected. A higher age‐related incidence of RH, CNSH, ccRCC and PNEN was detected in patients with a truncating variant (TV) compared to patients with a single amino‐acid substitution/deletion (AASD) (all p