Clinical and genetic findings in children with central nervous system arteriovenous fistulas
HHT is an autosomal‐dominant genetic disorder caused by a mutation of one of two genes: ENG, encoding endoglin, or ACVRL1, encoding activin receptor‐like kinase 1.3 These disrupting mutations lead to dysregulated angiogenesis with mucocutaneous telangiectasia and visceral arteriovenous shunts, especially pulmonary, hepatic, and cerebrospinal. The clinical picture is highly suggestive of HHT when at least three of the five Curaçao criteria are present.5 These criteria are the presence of epistaxis, telangiectasias, visceral arteriovenous malformations (AVMs), cerebral or spinal AVMs, and a first‐degree relative with HHT.
CM‐AVM1 is an autosomal‐dominant disorder caused by heterozygous RASA1 gene mutations. CM‐AVM1 presents with multifocal capillary malformations (CMs) associated with an increased rate of fast‐flow arteriovenous fistulas.2 CMs typically present as pale white halos, 1cm in diameter with a red punctate spot in the middle.2
CM‐AVM2 has been more recently described as an inherited autosomal‐dominant disorder caused by loss‐of‐function mutations in the EPHB4 gene.7 This syndrome is characterized by intracranial and extracranial AVMs, multifocal CMs, and telangiectasia.
These different diseases may be associated with brain or spinal AVFs.2 The purpose of this study is to assess the spectrum of genetic anomalies in a cohort of children with at least one brain or spinal pial AVF, and to describe their baseline clinical characteristics at the time of diagnosis and their respective outcomes.