HHT1

Hereditary hemorrhagic telangiectasia type 1 (HHT1) is a genetic vascular disorder characterized by dilated capillaries (telangiectasias) and arteriovenous malformations (AVMs) that can affect the skin, mucous membranes, and internal organs. HHT1 is caused by loss-of-function mutations in the ENG gene (endoglin) located on chromosome 9. Endoglin is a co-receptor in the transforming growth factor-beta (TGF-β) signaling pathway that regulates angiogenesis; reduced endoglin function leads to fragile vessels and abnormal vascular connections. The condition is inherited in an autosomal dominant manner with variable expressivity and penetrance.

Clinical features commonly include spontaneous, recurrent epistaxis (nosebleeds) and mucocutaneous telangiectasias on the lips, tongue, face, fingers, and oral mucosa. Visceral AVMs—most often in the lungs, liver, and brain—can cause serious complications such as hypoxemia, hemorrhage, high-output cardiac failure, stroke, or brain abscess. Iron deficiency anemia from chronic bleeding is frequent. Symptoms typically appear in childhood or adolescence but can emerge at any age.

Diagnosis relies on the Curaçao criteria: spontaneous epistaxis, multiple mucocutaneous telangiectasias in characteristic locations, visceral AVMs, and a family history of HHT. A definite diagnosis requires three criteria; two criteria indicate possible HHT, while one or none makes it less likely. Genetic testing can confirm ENG mutations and facilitate testing of at-risk relatives.

Management is multidisciplinary and aimed at reducing bleeding, treating AVMs, and preventing complications. Epistaxis can be managed with humidification, topical therapies, and laser or cautery; iron supplementation or transfusion may be needed. Pulmonary AVMs are often treated with transcatheter embolization; brain and liver AVMs are evaluated for potential intervention. Regular surveillance and genetic counseling are recommended.