VHL syndrome (von Hippel-Lindau)

Von Hippel-Lindau (VHL) disease is a heritable multisystem cancer syndrome that is associated with a germline mutation of the VHL tumour suppressor gene on the short arm of chromosome 3.

• the von Hippel-Lindau tumour suppressor gene (VHL) is located on the short arm of chromosome 3 (3p25-26)

Von Hippel-Lindau disease is a hereditary cancer syndrome predisposing carriers to the development of a panel of highly vascularized tumours such as central nervous system and retinal hemangioblastomas, endolymphatic sac tumours, clear-cell renal cell carcinomas, pheochromocytomas and pancreatic neuroendocrine tumours. The disease is the foremost cause of inherited renal cell carcinomas, which is induced by germline mutations of the VHL tumour-suppressor gene also inactivated in most sporadic renal cell carcinomas.

This disorder is not rare:

• about one in 36000 livebirths
• inherited as a highly penetrant autosomal dominant trait (ie, with a high individual risk of disease) with a high carriage rate of the causative gene in close relatives

Mean age at diagnosis is the mid-20s, often with retinal angioma as the first manifestation.

Reference:

1. Binderup MLM et al. Von Hippel-Lindau disease: updated guideline for diagnosis and surveillance. Eur J Med Genet. 2022;65:104538

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