Cerebral arteriopathy in ACTA2 mutations: a spectrum of disease highlighted by a case of variable penetrance in two siblings

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  • Department of Neurological Surgery, Wake Forest University School of Medicine, Winston-Salem, North Carolina
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Until recently, cerebral arteriopathy due to heterozygous mutations of the ACTA2 gene was considered a variant of moyamoya disease. However, radiographic analysis of patients with these mutations reveals a distinctive angiographic appearance from that seen in moyamoya disease. Several heterozygous missense ACTA2 mutations have been implicated in the development of this distinct cerebrovascular entity; however, the penetrance and systemic manifestations of these mutations vary based on the location of the amino acid replacement within the α–smooth muscle actin protein. The severity of the phenotype may also differ among patients within a single mutation type. There is limited literature on the safety and efficacy of revascularization procedures for ACTA2 arteriopathy, which have been limited to those patients with known Arg179His mutations. The authors provide a review of the breadth of mutations within the ACTA2 literature and report a case of two siblings with de novo ACTA2 Arg258Cys mutations with differing clinical courses, highlighting the utility of indirect revascularization with 8-year follow-up data. This case highlights the importance of early recognition of the angiographic appearance of ACTA2 cerebral arteriopathy and performance of genetic testing, as the location of the mutation impacts clinical presentation and outcomes.

ABBREVIATIONS DSA = digital subtraction angiography; EC-IC = extracranial-intracranial; EDAS = encephalodural synangiosis; ICA = internal carotid artery; MCA = middle cerebral artery; MSDMS = multisystemic smooth muscle dysfunction syndrome; PASL = pulse arterial spin labeling; PDA = persistent ductus arteriosus; TAAD = thoracic aortic aneurysm/dissection; TCD = transcranial Doppler; TIA = transient ischemic attack.

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Contributor Notes

Correspondence Christine Tschoe: Wake Forest Baptist Health, Winston-Salem, NC. ctschoe@gmail.com.

INCLUDE WHEN CITING Published online January 29, 2021; DOI: 10.3171/2020.8.PEDS20391.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

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