HHT2

HHT2, or hereditary hemorrhagic telangiectasia type 2, is the second genetic subtype of the autosomal dominant vascular disorder hereditary hemorrhagic telangiectasia (HHT). HHT is characterized by mucocutaneous telangiectasias and arteriovenous malformations (AVMs) that can affect the lungs, liver, brain, and gastrointestinal tract. HHT2 is caused by pathogenic variants in the ACVRL1 gene, which encodes activin receptor-like kinase 1, a receptor in the TGF-beta signaling pathway essential for vascular development and remodeling. Loss of ACVRL1 function leads to abnormal vessel formation and fragile vasculature. In some cases, HHT2 features overlap with other HHT types or with juvenile polyposis-HHT when SMAD4 is involved.

Clinical features include recurrent epistaxis beginning in adolescence and mucocutaneous telangiectasias on the lips, tongue, face, and fingertips. Visceral AVMs frequently affect the lungs, liver, and brain. Pulmonary AVMs can cause hypoxemia and carry risks of paradoxical emboli and brain abscess; hepatic AVMs may lead to high-output heart failure or portal hypertension; cerebral AVMs carry a risk of intracranial hemorrhage. Gastrointestinal bleeding from telangiectasias can contribute to iron-deficiency anemia.

Diagnosis relies on Curaçao criteria: spontaneous, recurrent epistaxis; mucocutaneous telangiectasias at typical sites; visceral AVMs; and a first-degree family member with HHT. Two criteria suggest possible HHT; three or more confirm the diagnosis. Genetic testing for ACVRL1 supports the diagnosis, and imaging testing screens for AVMs are recommended.

Management is supportive and multidisciplinary. Epistaxis management includes humidification, topical therapies, and laser ablation; iron supplementation is used for anemia. Antiangiogenic therapy, such as bevacizumab, can reduce epistaxis and GI bleeding in some patients. Interventional procedures or surgery address focal AVMs as indicated, with ongoing follow-up to monitor for new or evolving lesions.