To assess the spectrum of genetic anomalies in a cohort of children presenting at least one cerebral or spinal pial arteriovenous fistula (AVF), and to describe their clinical characteristics.
From 1988 to 2016, all consecutive patients with at least one cerebral or spinal pial AVF were screened for genetic disease. All patients aged <18 years were included. Symptoms associated with AVF were recorded: heart failure, neurological deficit/seizure, and hemorrhage. The outcome was assessed using the modified Rankin Scale and school performance in children with cerebral AVF and the American Spinal Injury Association impairment scale in children with spinal AVF.
Forty-three children were included. Twenty-five children were male and 18 were female. A germline mutation was identified in 23 probands (53.5 ± 14.9%): 8 in ENG (34.8 ± 14.2%), 1 in ACVRL1 (4.3 ± 6%) leading to a diagnosis of HHT, and 14 in RASA1 (60.9 ± 14.4%) leading to a diagnosis of capillary malformation/arteriovenous malformation type 1. No EphB4 gene mutation was identified. HHT patients presented a significantly lower rate of heart failure at diagnosis (p = 0.047). A trend toward an increased bleeding rate at presentation was observed in HHT (p = 0.069) and an increased rate of giant venous pouch in children in whom no mutation was identified (p = 0.097). Finally, an association with RASA1 mutation was observed in children with associated skin capillary hemangioma (p <  0001).
These results highlight the importance of genetic testing in this setting in view of the high frequency of gene mutations in pediatric cerebrospinal AVFs, and show the predominance of RASA1 over HHT mutations. Ann Neurol 2017;82:972-980.