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Betegségjelentés · Cancer

Von Hippel-Lindau Disease

Whole genome sequencing identifies VHL variants and enables the surveillance protocols that catch tumors early, when treatment options are broadest.

A betegségjelentés olyan ritka variánsokat keres, amelyekről ismert, hogy okozzák az általa lefedett betegségeket.

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A(z) condition ismertetése

An inherited condition caused by variants in the VHL gene, which leads to tumours and cysts in several organs. These include haemangioblastomas of the brain, spine and retina, clear cell kidney cancer, phaeochromocytoma and pancreatic tumours.

Von Hippel-Lindau (VHL) syndrome is caused by germline pathogenic variants in VHL, a gene encoding a protein component of an E3 ubiquitin ligase complex. Under normal oxygen, pVHL targets hypoxia-inducible factor (HIF) for degradation. When pVHL is dysfunctional, HIF accumulates constitutively, activating genes involved in angiogenesis, cell proliferation, and glucose metabolism, even in the presence of adequate oxygen. This pseudo-hypoxic state drives tumor formation specifically in highly vascularized organs. VHL follows Knudson's two-hit tumor suppressor model: the inherited germline variant inactivates one allele; somatic loss of the remaining allele initiates tumorigenesis.

Von Hippel-Lindau syndrome affects approximately 1 in 30,000-50,000 individuals, with penetrance exceeding 90% by age 65. The syndrome is characterized by multiple tumor types: hemangioblastomas of the brain, spinal cord, and retina (present in 60 to 80% of carriers), renal cysts and clear cell renal cell carcinoma (occurring in ~70%, the leading cause of mortality), pheochromocytoma/paraganglioma (10 to 20%), pancreatic neuroendocrine tumors and cysts, endolymphatic sac tumors, and epididymal/broad ligament cystadenomas. Approximately 10% of cases are de novo variants. Average age of VHL diagnosis is 26 years, with range from infancy to the seventh decade.

Identifying a VHL pathogenic variant dramatically changes clinical management. It triggers comprehensive lifelong surveillance beginning in childhood: annual retinal examination from age 1, annual blood pressure monitoring from age 5, annual abdominal MRI from age 15, and biennial brain/spine MRI. This surveillance approach catches renal cell carcinomas and pheochromocytomas at early stages when kidney-sparing surgery is possible, preserving renal function through multiple interventions over a lifetime. Belzutifan, an FDA-approved HIF-2α inhibitor, offers targeted therapy for VHL-associated renal cell carcinoma. Cascade testing identifies relatives at risk before tumors develop.

VHL genotype-phenotype correlations are clinically important: Type 1 variants (no pheochromocytoma risk) have different surveillance protocols than Type 2A/2B/2C variants (pheochromocytoma risk, requiring additional screening).

A vizsgált betegség

Autoszomális domináns

A VHL-related tumour predisposition syndrome with haemangioblastomas, renal cell carcinoma, phaeochromocytoma and pancreatic neuroendocrine tumours.

Mit változtat a diagnózis

Lifelong multiorgan surveillance, kidney-sparing surgery, belzutifan (HIF-2α inhibitor), cascade testing, prenatal counseling

Vizsgált gének

Más néven

cerebroretinal angiomatosis; familial cerebelloretinal angiomatosis; Lindau disease; VHL; VHL syndrome; VHL-related von Hippel-Lindau disease; Von Hippel-Lindau syndrome; Von Hippel-Lindau syndrome (VHL); von Hippel-Lindau syndrome, modifier of

MONDO:0008667OMIM 193300Orphanet 892MedGen 42458

Miért a teljes genom szekvenálás

The VHL gene is small, but approximately 20% of pathogenic variants are large deletions, requiring specialized analysis standard sequencing does not provide.

VHL deletions require deletion-duplication analysis standard panels lack

VHL is a relatively small gene (3 exons), which typically allows high detection rates with standard sequencing. However, approximately 20% of VHL pathogenic variants are partial or complete gene deletions. Standard short-read sequencing excels at detecting point mutations and small insertions/deletions but struggles with large structural rearrangements. Many commercial panels do not include deletion/duplication analysis for VHL, requiring separate, often cumbersome testing. Mosaic VHL variants at low allelic fractions may be missed by standard sequencing depth. Whole genome sequencing detects both point mutations and structural variants in a single analysis.

A VHL finding opens a surveillance protocol that saves lives

Confirmation of VHL triggers the most comprehensive single-gene surveillance protocol in medical genetics. Annual retinal exams from age 1 catch optic pathway complications early. Annual abdominal MRI from age 15 detects kidney cancers and pheochromocytomas at early stages, when kidney-sparing surgery preserves renal function across multiple operations spanning a lifetime. Belzutifan (Welireg), an FDA-approved HIF-2α inhibitor, offers targeted therapy specifically for VHL-associated renal cell carcinoma, representing a genotype-matched treatment option.

További cancer conditions

Minden feltétel →

Egy teszt. Egy életen át tartó válaszok.

Egy csomag, házhoz szállítva. Az egész genomját a diagnosztikai döntésekhez használt klinikai színvonalon szekvenáljuk. Orvos számára is használható jelentéseit 6–8 héten belül küldjük el a Genome Manager-be. Ezek tartósan érvényesek, és a tudomány fejlődésével frissülnek.

449 $-tól

Ingyenes szállítás · Eredmények 6–8 hét alatt

Kérem a Genome Testemet