The VASCERN HHT working group established a clear definition of Hereditary Haemorrhagic Telangiectasia (HHT) for ORPHANET in 2019 (see here). HHT is a single, relatively common “Rare” Vascular Disease with distinct screening and management recommendations. It is marked by the presence of non-randomly occurring abnormal vascular structures that give rise to various complications. Currently available treatments focus on managing symptoms rather than addressing the underlying pathophysiology.
Unlike the other ERN components, HHT’s clinical phenotype is primarily defined by chronic bleeding from abnormal vascular structures, as well as the occurrence of paradoxical emboli through pulmonary arteriovenous malformations (AVMs) and wider circulatory consequences resulting from systemic AVMs. These complications are often exacerbated by anemia and low oxygen levels.
Given the diverse range of manifestations, HHT may require the involvement of specialists from various medical fields. Small telangiectasia can lead to nosebleeds (epistaxis), gastrointestinal bleeding and iron deficiency anaemia. Larger AVMs in the pulmonary, hepatic, and cerebral circulations may hemorrhage. Pulmonary AVMs cause preventable ischemic strokes, cerebral abscesses, and hypoxaemia, and systemic AVMs demand higher cardiac outputs aggravated by iron deficiency and/or hypoxaemia. Approximately 1 in 100 women die during pregnancy, and the SMAD4 subgroup (~2%) faces additional risks of aortic rupture, juvenile polyposis and gastrointestinal cancers. Paradoxically, when appropriately managed, individuals with HHT can have a good life expectancy with likely explanations, including apparent protection from certain cancers and myocardial infarctions.
The clinical diagnosis of HHT is based on the Curaçao criteria established by Shovlin et al, 2000. Molecular diagnosis is available for the ACVRL1 (ALK1), ENG, and SMAD4 pathogenic variants (also known as “mutations”), which are found in over 90% of patients with a definite clinical diagnosis of HHT.
Bases for the estimated incidence and prevalence numbers: 500 Million inhabitants within European union with about 6 million newborns annually.