[Rendu-Osler disease: clinical and molecular update]

Area of Science:

• Vascular Biology
• Genetics
• Epidemiology

Background:

• Hereditary Hemorrhagic Telangiectasia (HHT), or Rendu-Osler disease, affects 1 in 5,000-8,000 people.
• Characterized by frequent nosebleeds, mucocutaneous and visceral telangiectasias, and an autosomal-dominant inheritance pattern.
• A French epidemiological study noted a higher prevalence in the Haut-Jura mountains.

Purpose of the Study:

• To review the genetic basis and pathogenesis of HHT.
• To explore the role of TGFβ superfamily signaling in HHT.
• To discuss current and future therapeutic strategies for HHT.

Main Methods:

• Review of scientific literature on HHT genetics and molecular pathways.
• Analysis of epidemiological data regarding HHT prevalence.
• Discussion of animal models and their relevance to HHT pathogenesis.

Main Results:

• HHT is linked to mutations in genes (ENG, ACVRL1, MADH4) affecting TGFβ signaling in vascular endothelial cells.
• The BMP9/ALK1/endoglin pathway is crucial for angiogenesis maturation.
• Defects in endoglin or ALK1 in mice replicate HHT phenotypes, supporting endothelial hyperproliferation.

Conclusions:

• HHT pathogenesis involves endothelial hyperproliferation, particularly in the angiogenesis maturation phase.
• Current HHT management is primarily symptomatic.
• The angiogenic nature of HHT suggests potential future therapies using anti-angiogenic drugs.