Abstract TP503: Screening Algorithm for Hereditary Hemorrhagic Telangiectasia in Pediatric Brain AVM

Abstract

Background: Hereditary Hemorrhagic Telangiectasia (HHT) is a rare cause of familial arteriovenous malformation (AVM) which may present symptomatically in the brain, spine, pulmonary, or hepatic circulation. Symptoms and signs of HHT - including epistaxis, GI bleeding, and cutaneous telangiectasia - may not be manifest at the time of AVM diagnosis. Natural history studies suggesting a more benign course for HHT-associated AVM compared to sporadic AVM may reflect a sampling bias if the true frequency of HHT is under-estimated. In this study, we report our experience with HHT screening in a population with pediatric brain AVM. Methods: Patients followed in the multidisciplinary Cincinnati Children’s Hospital Cerebrovascular Center are interviewed by a genetics counselor after identification of a brain AVM. A comprehensive medical and family history are collected and patients are offered screening for HHT using a 5 gene panel (Ambry Genetics: ACVRL1, ENG, SMAD4, RASA1, GDF2). Further testing with bubble echocardiogram and skin examination is offered to identify clinical criteria for HHT per Curacao criteria. Results: Brain AVM was identified in 12 patients followed in our center with age range 5 weeks to 17 years at AVM diagnosis. Recurrent epistaxis was present in 6 (50%) of our patients. Family history is negative for HHT in all cases although 75% of patients had at least 1 first degree relative with recurrent epistaxis. Additional diagnostics were completed in 10 of 12 patients, including genetic testing in 9 individuals. No pathogenic mutations were identified in this small cohort but 2 patients showed variants of unknown significance in ENG (p.R3C and p.E41K). Of the 10 patients who completed additional screening for HHT, 2 met criteria for definite HHT (ages 3 and 17) and 2 for possible HHT (ages 2 and 10). Conclusions: In our cohort of pediatric brain AVM patients, 33% met criteria for possible or definite HHT. The clinical symptoms and signs of HHT emerge over time. Using a standard diagnostic algorithm for reassessment of Curacao criteria may help facilitate correct and timely diagnosis. For cases confirmed with definite HHT, genetic counseling and gene testing should be considered.