Clinical Updates on Hereditary Hemorrhagic Telangiectasia (HHT) and Other Vascular Diseases

Dear Colleagues,

Hereditary hemorrhagic telangiectasia (HHT) is listed in both the capillary (telangiectasia subgroup) and the arteriovenous malformation (AVM) groups in the 2018 classification from the International Society for the Study of Vascular Anomalies (ISSVA). In 2024, thirty years after the identification of the first causative gene, endoglin (ENG), the diagnosis of HHT remains a challenge, as it is a rare disease (with a prevalence of 1:5000–1:10,000) with age-related penetrance of its multisystemic symptoms, and in addition, congenital pulmonary and cerebral AVMs are most often asymptomatic until emerging as severe, acute complications in a subset of patients. The involved disciplines might address the symptoms one by one, often without the chance to assemble the underlying syndrome. All variant types (missense, nonsense, splice-site, frameshift, in-frame deletions and insertions, and finally, large deletions and insertions in 10% of cases) have been described throughout the causative ENG, ACVRL1, and SMAD4 genes. In 2021, 510 ENG and 572 ACVRL1 variants were known.

Despite the unequivocal diagnostic criteria published in 2000 and the international guidelines for the diagnosis and management of HHT issued in 2011 and revised in 2020, the average diagnostic time lag (the interval between the first symptoms and the diagnosis of HHT) is still almost three decades for probands and only somewhat shorter for at-risk family members. Other vascular diseases resembling more or less HHT, especially the capillary malformation-arteriovenous malformation (CM-AVM) syndromes 1 and 2 (caused by RASA1 and EPHB4 mutations, respectively), are even less prevalent (approx. 1:100,000). Considering the above clinical and genetic peculiarities of the above conditions, their diagnosis and therapy is the subject of extensive research. Groups from all clinical specialties and genetic institutions are encouraged to submit their original research and review manuscripts to this Special Issue of the Journal of Clinical Medicine.

Dr. Tamás Major
Guest Editor

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• hereditary hemorrhagic telangiectasia (HHT)
• arteriovenous malformations
• embolization
• VEGF
• capillary malformation-arteriovenous malformation