Background and purpose: Pathogenic variants in the ACTA2 gene cause a distinctive arterial phenotype that has recently been described to be associated with brain malformation. Our objective was to further characterize gyral abnormalities in patients with ACTA2 pathogenic variants as per the 2020 consensus recommendations for the definition and classification of malformations of cortical development.
Materials and methods: We performed a retrospective, multicentric review of patients with proved ACTA2 pathogenic variants, searching for the presence of malformations of cortical development. A consensus read was performed for all patients, and the type and location of cortical malformation were noted in each. The presence of the typical ACTA2 arterial phenotype as well as demographic and relevant clinical data was obtained.
Results: We included 13 patients with ACTA2 pathogenic variants (Arg179His mutation, n = 11, and Arg179Cys mutation, n = 2). Ninety-two percent (12/13) of patients had peri-Sylvian dysgyria, 77% (10/13) had frontal dysgyria, and 15% (2/13) had generalized dysgyria. The peri-Sylvian location was involved in all patients with dysgyria (12/12). All patients with dysgyria had a characteristic arterial phenotype described in ACTA2 pathogenic variants. One patient did not have dysgyria or the characteristic arterial phenotype.
Conclusions: Dysgyria is common in patients with ACTA2 pathogenic variants, with a peri-Sylvian and frontal predominance, and was seen in all our patients who also had the typical ACTA2 arterial phenotype.
© 2022 by American Journal of Neuroradiology.