Clinical and neuroimaging features of a familial pathogenic ACTA2 variant as a model of a vascular neurocristopathy

The clinical and neuroimaging findings of a family with a variant ACTA2 gene (c351C > G), presenting with smooth muscle dysfunction in structures of neural crest derivation, are discussed. The combination of aortic abnormalities, patent ductus arteriosus, congenital mydriasis and distinctive cerebrovascular and brain morphological abnormalities characterise this disorder. Two sisters, heterozygous for the variant, and their mother, a mosaic, are presented. Brain parenchymal changes are detailed for the first time in a non-Arg179His variant. Radiological features of the petrous canal and external carotid are highlighted. We explore the potential underlying biological and embryological mechanisms.

Automated summary

This paper discusses the clinical and neuroimaging findings of a family with a variant ACTA2 gene (c351C > G). The disorder is characterized by a combination of aortic abnormalities, patent ductus arteriosus, congenital mydriasis, and distinctive cerebrovascular and brain morphological abnormalities. The report presents two sisters who are heterozygous for the variant and their mother who is a mosaic. It also provides detailed brain parenchymal changes for the first time in a non-Arg179His variant and highlights the radiological features of the petrous canal and external carotid. The potential underlying biological and embryological mechanisms are explored.