hht

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a genetic vascular disorder characterized by abnormal blood vessel formation. It leads to mucocutaneous telangiectasias and arteriovenous malformations (AVMs) that can involve multiple organs. The condition is lifelong and can vary widely in severity between individuals.

HHT is typically inherited in an autosomal dominant pattern. It most commonly involves mutations in ENG (HHT1) or ACVRL1 (HHT2), with SMAD4 mutations associated with combined juvenile polyposis/HHT in some cases. The disorder affects about 1 in 5,000 to 8,000 people. Penetrance is high, but clinical features vary in expression.

Clinical features often begin with recurrent nosebleeds (epistaxis) and mucocutaneous telangiectasias on the lips, tongue, face, and fingertips. Visceral AVMs can occur in the lungs, liver, brain, and spine. Pulmonary AVMs may cause shortness of breath and hypoxemia and can permit paradoxical emboli; brain AVMs raise the risk of hemorrhagic stroke or seizures; hepatic AVMs can lead to abdominal symptoms and high-output heart failure.

Diagnosis relies on the Curaçao criteria: spontaneous epistaxis, mucocutaneous telangiectasia, visceral AVMs, and family history. Definite HHT is 3 or more criteria; probable is 2 criteria; possible is 1. Genetic testing can confirm a pathogenic variant in ENG, ACVRL1, or SMAD4.

Management is multidisciplinary and supportive. Epistaxis is treated with humidification, topical therapies, laser or cautery, and iron supplementation for anemia. AVMs may be managed with embolization for pulmonary lesions, neurosurgical or endovascular treatment for brain AVMs, and monitoring or liver-directed therapies for hepatic involvement. People with HHT should receive regular screening and, for those with pulmonary AVMs, antibiotic prophylaxis before dental or procedures that may cause bacteremia.