Gene Mutations Related to Pathogenesis and Development of Cerebral Arteriovenous Malformations in Pediatric Populations

Abstract

Abstract INTRODUCTION Cerebral arteriovenous malformations (AVMs) are the most common cause of spontaneous intracranial hemorrhage in pediatric patients. Recurrence after complete surgical resection is a recognized risk that occurs primarily in children. While Pediatric Neurosurgery practices traditionally focus on clinical management, recent advances have found gene mutations to play a role in pathogenesis and development of AVMs It is not known how many pediatric AVMs are sporadic versus arising from familial inheritance patterns. We aimed to see how identified genetic mutations are represented in our AVM patient population in Texas and the southern United States. METHODS We developed a multidiscipinary pediatric neurovascular program at our institution. Patients and families were screened in their first-time and/or follow-up outpatient clinic encounters by our hematologist-oncologist and genetics counsellor from the Pediatric Vascular Anomalies program. Genetic testing recommendations and results were recorded in our IRB-approved ongoing prospective neurovascular database. RESULTS 50 patients were screened in Vascular Anomalies program. Diagnoses ranged from AVMs (n = 20), cerebral cavernous malformations (n = 13), non-NF/non-sickle-cell moyamoya (n = 7), and other lesions such as cerebral proliferative angiopathy and megelencephaly-capillary malformation. Of the 50 patients, 30 underwent genetic testing. 7 had identified mutations. 3 patients with cavernous angiomas had Krit1 mutations. 2 patients with AVMs had Rasa1 mutations, and 2 patients with megenecephaly-capillary malformations had PIK3CA mutations. CONCLUSION These preliminary findings highlight the importance of thinking beyond neurosurgical intervention for pediatric neurovascular diseases. Genetic mutations have been found in 23% of patients screened thus far. Such findings provide insight into disease biology and may likely have clinical implications for risk assessment, family screening, and follow-up surveillance. Further work needs to be done to capture all our AVM population for genetic screening over time, while expanding our neurovascular program's study focus to encompass all neurovascular pathologies.