# Doença de von Hippel-Lindau

> Página oficial: https://raras.org/doenca/doenca-de-von-hippel-lindau
> Fonte: Raras.org — Banco de Dados de Doenças Raras em Português (CC BY-NC-SA 4.0)
> Última atualização: 2026-05-07

## Identificadores

- **ORPHA**: 892 — https://www.orpha.net/en/disease/detail/892
- **CID-10**: Q85.8
- **OMIM**: OMIM:193300 — https://omim.org/entry/193300

## Descrição clínica

Síndrome de predisposição familiar para cancro associada a uma variedade de neoplasias malignas e benignas, mais frequentemente hemangioblastoma retiniano, cerebeloso e espinal, carcinoma de células renais (CCR) e feocromocitoma/paraganglioma.

## Epidemiologia e herança

- **Prevalência**: 1-9 / 100 000
- **Padrão de herança**: Autosomal dominant

## Sinais e sintomas (49 fenótipos HPO)

- **Anomalia do desenvolvimento do giro frontal inferior** — HPO: HP:0011462
- **Herança autossômica dominante** — HPO: HP:0000006
- **Carcinoma de células renais** — HPO: HP:0005584 (Frequente (79-30%))
- **Perda visual** — HPO: HP:0000572 (Ocasional (29-5%))
- **Arritmia** — HPO: HP:0011675 (Ocasional (29-5%))
- **Vertigem** — HPO: HP:0002321 (Ocasional (29-5%))
- **Paraganglioma** — HPO: HP:0002668 (Raro (<5%))
- **Retinopatia hipertensiva** — HPO: HP:0001095 (Ocasional (29-5%))
- **Hemangioblastoma cerebelar** — HPO: HP:0006880 (Frequente (79-30%))
- **Adenoma de células das ilhotas pancreáticas** — HPO: HP:0008261 (Ocasional (29-5%))
- **Descolamento de retina** — HPO: HP:0000541 (Raro (<5%))
- **Neoplasia do pâncreas** — HPO: HP:0002894 (Raro (<5%))
- **Anormalidade do olho** — HPO: HP:0000478 (Muito frequente (99-80%))
- **Hipertensão** — HPO: HP:0000822 (Frequente (79-30%))
- **Cistos pancreáticos** — HPO: HP:0001737 (Ocasional (29-5%))
- **Papiledema** — HPO: HP:0001085 (Ocasional (29-5%))
- **Nível elevado de catecolamina circulante** — HPO: HP:0003334 (Ocasional (29-5%))
- **Catecolaminas urinárias elevadas** — HPO: HP:0011976 (Frequente (79-30%))
- **Fraqueza muscular de membro superior** — HPO: HP:0003484 (Ocasional (29-5%))
- **Infarto do miocárdio** — HPO: HP:0001658 (Raro (<5%))
- **Aumento da pressão intracraniana** — HPO: HP:0002516 (Raro (<5%))
- **Tumor endócrino pancreático** — HPO: HP:0030405 (Ocasional (29-5%))
- **Feocromocitoma adrenal** — HPO: HP:0006748 (Frequente (79-30%))
- **Dor nas costas** — HPO: HP:0003418 (Ocasional (29-5%))
- **Policitemia** — HPO: HP:0001901 (Raro (<5%))
- **Hemangioma capilar retiniano** — HPO: HP:0009711 (Frequente (79-30%))
- **Fraqueza muscular distal do membro inferior** — HPO: HP:0009053 (Ocasional (29-5%))
- **Ansiedade** — HPO: HP:0000739 (Ocasional (29-5%))
- **Função ventricular esquerda anormal** — HPO: HP:0005162 (Ocasional (29-5%))
- **Múltiplos cistos renais** — HPO: HP:0005562 (Ocasional (29-5%))
- **Hiperidrose** — HPO: HP:0000975 (Ocasional (29-5%))
- **Edema macular** — HPO: HP:0040049 (Ocasional (29-5%))
- **Miocardite** — HPO: HP:0012819 (Raro (<5%))
- **Palidez** — HPO: HP:0000980 (Ocasional (29-5%))
- **Acidente vascular cerebral** — HPO: HP:0001297 (Ocasional (29-5%))
- **Cefaleia** — HPO: HP:0002315 (Ocasional (29-5%))
- **Cisto epididimário** — HPO: HP:0030424 (Raro (<5%))
- **Dor abdominal** — HPO: HP:0002027 (Ocasional (29-5%))
- **Cistadenoma papilar do epidídimo** — HPO: HP:0009715 (Ocasional (29-5%))
- **Cardiomiopatia** — HPO: HP:0001638 (Ocasional (29-5%))
- _...e mais 9 sintomas. Ver https://raras.org/doenca/doenca-de-von-hippel-lindau._

## Genes associados (2)

- **VHL** — von Hippel-Lindau disease tumor suppressor [Disease-causing germline mutation(s) in]
  - Função: Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex (PubMed:10944113, PubMed:17981124, PubMed:19584355). Seems to act as a target rec
- **CCND1** — G1/S-specific cyclin-D1 [Modifying germline mutation in]
  - Função: Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S tran

## Medicamentos em desenvolvimento (6)

- BELZUTIFAN — Fase Phase 4 (Endothelial PAS domain-containing protein 1 inhibitor)
- VATALANIB — Fase Phase 2 (Vascular endothelial growth factor receptor inhibitor)
- PAZOPANIB HYDROCHLORIDE — Fase Phase 2 (Vascular endothelial growth factor receptor inhibitor)
- PAZOPANIB — Fase Phase 2 (Vascular endothelial growth factor receptor inhibitor)
- DOVITINIB — Fase Phase 2 (Fibroblast growth factor receptor 3 inhibitor)
- SUNITINIB — Fase Phase 2 (Vascular endothelial growth factor receptor inhibitor)
- Fonte: https://platform.opentargets.org/disease/MONDO_0008667

## Ensaios clínicos ativos (21)

- **NCT04074135** [RECRUITING]: Natural History and Management of Von Hippel-Lindau (VHL) Associated Pancreatic Neuroendocrine Tumors — https://clinicaltrials.gov/study/NCT04074135
- **NCT07405164** [RECRUITING]: Extension Study for Participants in Studies That Include Belzutifan (MK-6482-043/LITESPARK-043) — https://clinicaltrials.gov/study/NCT07405164
- **NCT04924075** [RECRUITING]: Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Solid Tumors With HIF-2α Related Genetic Alterations (MK-6482-015) — https://clinicaltrials.gov/study/NCT04924075
- **NCT01496625** [RECRUITING]: National Eye Institute Biorepository for Retinal Diseases — https://clinicaltrials.gov/study/NCT01496625
- **NCT07171905** [RECRUITING]: CAT-VHL Exploring the Role of Carbonic Anhydrase IX as Diagnostic and Theranostic Target in Von-Hippel Lindau Disease — https://clinicaltrials.gov/study/NCT07171905
- **NCT03050268** [RECRUITING]: Familial Investigations of Childhood Cancer Predisposition — https://clinicaltrials.gov/study/NCT03050268
- **NCT06573723** [RECRUITING]: Institutional Registry of Rare Diseases — https://clinicaltrials.gov/study/NCT06573723
- **NCT05955014** [RECRUITING]: Data Collection Protocol for Patients With Von Hippel Lindau Disease — https://clinicaltrials.gov/study/NCT05955014
- **NCT07167329** [RECRUITING]: Real-World Effectiveness and Pharmacogenetics of Belzutifan in VHL Syndrome: The BELIEVE-VHL Trial — https://clinicaltrials.gov/study/NCT07167329
- **NCT06553339** [RECRUITING]: A Study of HS-10516 in Patients With VHL Syndrome Associated Tumors — https://clinicaltrials.gov/study/NCT06553339

## Doenças relacionadas (por similaridade fenotípica)

- [Neoplasias endócrinas múltiplas](https://raras.org/doenca/neoplasias-endocrinas-multiplas) — ORPHA:100094 — 15 sintomas em comum
- [Neoplasia endócrina múltipla](https://raras.org/doenca/neoplasia-endocrina-multipla) — ORPHA:276161 — 12 sintomas em comum
- [Feocromocitomas-paraganglioma hereditário](https://raras.org/doenca/29072) — ORPHA:29072 — 12 sintomas em comum
- [Encefalite infecciosa](https://raras.org/doenca/encefalite-infecciosa) — ORPHA:98252 — 11 sintomas em comum
- [Hemopatia mieloide](https://raras.org/doenca/hemopatia-mieloide) — ORPHA:171895 — 10 sintomas em comum
- [Doença Fabry](https://raras.org/doenca/doenca-fabry) — ORPHA:324 — 10 sintomas em comum
- [Policitemia](https://raras.org/doenca/policitemia) — ORPHA:98427 — 9 sintomas em comum
- [Miopatia e fasciite inflamatórias adquiridas](https://raras.org/doenca/miopatia-e-fasciite-inflamatorias-adquiridas) — ORPHA:98482 — 9 sintomas em comum
- [Doença mieloproliferativa crônica](https://raras.org/doenca/doenca-mieloproliferativa-cronica) — ORPHA:98274 — 9 sintomas em comum
- [Tumor endócrino enteropancreático](https://raras.org/doenca/tumor-endocrino-enteropancreatico) — ORPHA:100092 — 8 sintomas em comum

## Importante

O Raras **não diagnostica e não prescreve**. Esta página é educativa e informativa.
Pacientes devem consultar profissionais de saúde qualificados para decisões clínicas.

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**Citação sugerida**: Raras.org — Doença de von Hippel-Lindau. Disponível em: https://raras.org/doenca/doenca-de-von-hippel-lindau
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