Genotype-Phenotype Correlations In Children With Hht

Hereditary hemorrhagic telangiectasia (HHT), a rare autosomal dominant disease mostly caused by mutations in three known genes (ENG,ACVRL1, andSMAD4), is characterized by the development of vascular malformations (VMs). Patients with HHT may present with mucocutaneous telangiectasia, as well as organ arteriovenous malformations (AVMs) of the central nervous system, lungs, and liver. Genotype-phenotype correlations have been well described in adults with HHT. We aimed to investigate genotype-phenotype correlations among pediatric HHT patients. Demographic, clinical, and genetic data were collected and analyzed in 205 children enrolled in the multicenter Brain Vascular Malformation Consortium HHT Project. A chi-square test was used to determine the association between phenotypic presentations and genotype. Among 205 patients (age range: 0-18 years; mean: 11 years),ENGmutation was associated with the presence of pulmonary AVMs (p< 0.001) and brain VM (p< 0.001). The presence of a combined phenotype-defined as both pulmonary AVMs and brain VMs-was also associated withENGmutation. Gastrointestinal bleeding was rare (4.4%), but was associated withSMAD4genotype (p< 0.001). We conclude that genotype-phenotype correlations among pediatric HHT patients are similar to those described among adults. Specifically, pediatric patients withENGmutation have a greater prevalence of pulmonary AVMs, brain VMs, and a combined phenotype.