Current HHT genetic overview in Spain and its phenotypic correlation: data from RiHHTa registry

Area of Science:

• Genetics
• Vascular Biology
• Rare Diseases

Background:

• Hereditary Hemorrhagic Telangiectasia (HHT) is a rare, autosomal dominant vascular disorder.
• Disease-causing variants in endoglin (ENG) and ACVRL1 genes account for over 90% of diagnosed HHT cases.

Purpose of the Study:

• To describe genetic variants in HHT patients within Spain.
• To assess genotype-phenotype correlations in Spanish HHT patients using the RiHHTa registry.

Main Methods:

• Utilized data from the Computerized Registry of Hereditary Hemorrhagic Telangiectasia (RiHHTa) in Spain.
• Analyzed genetic variants in endoglin (ENG) and ACVRL1 genes.
• Correlated genetic findings with clinical phenotypes based on Curaçao criteria.

Main Results:

• ACVRL1 variants (68.1%) were more frequent than ENG variants (31.8%) in the studied Spanish HHT cohort.
• ENG variant patients were younger at diagnosis (36.9 vs 45.7 years) and had higher rates of pulmonary (71.4%) and cerebral (17.6%) AVMs.
• ACVRL1 variant patients more frequently presented with anemia (56.7%) and showed higher cardiac index and hepatic functional blood test levels.

Conclusions:

• ACVRL1 gene variants are more prevalent than ENG variants in Spanish HHT patients.
• ENG variants are associated with earlier diagnosis and a higher incidence of arteriovenous malformations (AVMs) in the lungs and brain.
• ACVRL1 variants correlate with increased prevalence of symptomatic liver disease and anemia.