Germline genetic mutations in pediatric cerebrovascular anomalies: a multidisciplinary approach to screening, testing, and management

Melissa A. LoPresti, Rebecca Y. Du, Jae Eun Lee, Ionela Iacobas, Katie Bergstrom, Samuel G. McClugage, Sandi K. Lam*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


OBJECTIVE Genetic alterations are increasingly recognized as etiologic factors linked to the pathogenesis and development of cerebrovascular anomalies. Their identification allows for advanced screening and targeted therapeutic approaches. The authors aimed to describe the role of a collaborative approach to care and genetic testing in pediatric patients with neurovascular anomalies, with the objectives of identifying what genetic testing recommendations were made, the yield of genetic testing, and the implications for familial screening and management at present and in the future. METHODS The authors performed a descriptive retrospective cohort study examining pediatric patients genetically screened through the Pediatric Neurovascular Program of a single treatment center. Patients 18 years of age and younger with neurovascular anomalies, diagnosed radiographically or histopathologically, were evaluated for germline genetic testing. Patient demographic data and germline genetic testing and recommendation, clinical, treatment, and outcome data were collected and analyzed. RESULTS Sixty patients were included; 29 (47.5%) were female. The mean age at consultation was 11.0 ± 4.9 years. Diagnoses included cerebral arteriovenous malformations (AVMs) (n = 23), cerebral cavernous malformations (n = 19), non-neurofibromatosis/non–sickle cell moyamoya (n = 8), diffuse cerebral proliferative angiopathy, and megalencephaly–capillary malformation. Of the 56 patients recommended to have genetic testing, 40 completed it. Genetic alterations were found in 13 (23%) patients. Four patients with AVMs had RASA1, GDF2, and ACVRL1 mutations. Four patients with cavernous malformations had Krit1 mutations. One with moyamoya disease had an RNF213 mutation. Three patients with megalencephaly–capillary malformation had PIK3CA mutations, and 1 patient with a cavernous sinus lesion had an MED12 mutation. The majority of AVM patients were treated surgically. Patients with diffuse cerebral proliferative angiopathy were treated medically with sirolimus. At-risk relatives of 3 patients positive for genetic anomalies had also been tested. CONCLUSIONS This study demonstrates a role for exploring genetic alterations in the identification and treatment of pediatric neurovascular disease pathogenesis. Germline genetic mutations were found in almost one-quarter of the patients screened in this study, results that helped to identify medically targeted treatment modalities for some pediatric neurovascular patients. Insight into the genetic etiology of vascular anomalies may provide broader clinical implications for risk assessment, family screening, follow-up surveillance, and medical management.

Original languageEnglish (US)
Pages (from-to)212-220
Number of pages9
JournalJournal of Neurosurgery: Pediatrics
Issue number3
StatePublished - Mar 2023


  • arteriovenous malformation
  • cerebrovascular anomalies
  • genetic mutation
  • genetic screening
  • neurovascular pathology
  • pediatric
  • vascular disorders

ASJC Scopus subject areas

  • Surgery
  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology


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