Clinical and Genetic Characteristics of Children with Hereditary Hemorrhagic Telangiectasia (HHT) in Israel

Introduction: Hereditary Hemorrhagic Telangiectasia (HHT, Osler-Weber-Rendu) is an autosomal dominant vascular dysplasia with a prevalence of 1:5,000-8,000, characterized by mucocutaneus telangiectases and arteriovenous malformations (AVMs) in visceral organs. Clinical criteria were established for HHT diagnosis; however, symptoms and signs can develop in late childhood, making the clinical diagnosis of HHT in children challenging. Objective: To describe the clinical and genetic features of children with HHT and to assess the sensitivity of the diagnostic criteria in children. Methods: All children (aged 0-20 years) referred to the National HHT center during 2003-2019 were included. Screening protocol includes: clinical assessment, genetic testing and screen for pulmonary and cerebral AVMs. Clinical and genetic information was collected and analyzed.

Results: 178 children were screened. 76 (42.7%) had a clinical or genetic diagnosis of HHT. Mean age at referral was 11±5.4 years. Epistaxis was present in 69 (92%). Mean age of epistaxis onset was 5.8±4.3 years. Pulmonary AVMs were detected in 24 (40%) children, 17 of them requiring catheterization. Cerebral AVMs were detected in 20%. Three children with cerebral AVMs presented with neurological sequelae prior to screening. Sensitivity of the clinical criteria in all children with genetically proven HHT was 64.5%.

Conclusions: Visceral AVMs are common in children with HHT and can result in significant sequelae. The sensitivity of clinical criteria-based diagnosis is low and can result in underdiagnosis and life-threatening complications. Our study emphasizes the importance of screening for visceral AVMs and the role of genetic testing for every child with suspected HHT.