Neonatal Stroke and Progressive Leukoencephalopathy in a Child With an ACTA2 Mutation

Abstract

Mutations in the smooth muscle–specific isoform of α-actin (ACTA2) cause vascular smooth muscle dysfunction leading to aortic aneurysm and moyamoya syndrome. A unique R179H mutation in ACTA2 has been reported to result in widespread smooth muscle dysfunction affecting vascular and extravascular smooth muscles. We report a 7-year-old girl with an ACTA2 R179H mutation manifesting with neonatal seizures due to multifocal infarcts, asymmetric motor deficits, global developmental delay, spasticity, congenital bilateral mydriasis, and a large patent ductus arteriosus. Serial magnetic resonance imaging (MRI) of the brain over 7 years showed diffuse supratentorial white matter abnormalities consistent with a progressive leukoencephalopathy. Magnetic resonance angiography of the cerebral vessels showed stenosis in the terminal portion of the bilateral internal carotid arteries with fusiform dilation of the proximal segment. Neonatal onset of neurologic symptoms in ACTA2 mutations has not been previously reported. R179H mutation in ACTA2 represents the severe end of the disease spectrum.

Keywords

moyamoya syndrome congenital mydriasis neonatal leukoencephalopathy stroke

Get full access to this article

View all access options for this article.

References

Guo

Pannu

Tran-Fadulu

. Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections. Nat Genet. 2007;39:1488–1493.

Milewicz

Ostergaard

Ala-Kokko

. De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction. Am J Med Genet A. 2010;152A:2437–2443.

Guo

Papke

Tran-Fadulu

. Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and moyamoya disease, along with thoracic aortic disease. Am J Hum Genet. 2009;84:617–627.

Roder

Peters

Kasuya

. Analysis of ACTA2 in European moyamoya disease patients. Eur J Paediatr Neurol. 2011;15:117–122.

Khan

Schinzel

Shuknecht

. Moyamoya angiopathy with dolichoectatic internal carotid arteries, patent ductus arteriosus and pupillary dysfunction: a new genetic syndrome? Eur Neurol. 2004;51:72–77.

Lemire

Buncic

Kennedy

. Congenital mydriasis, patent ductus arteriosus, and congenital cystic lung disease: new syndromic spectrum? Am J Med Genet. 2004;131:318–319.

Ades

Davies

Haan

. Aortic dissection, patent ductus arteriosus, iris hypoplasia and brachytelephalangy in a male adolescent. Clin Dysmorphol. 1999;8:269–276.

Richer

Milewicz

Gow

. R179H mutation in ACTA2 expanding the phenotype to include prune-belly sequence and skin manifestations. Am J Med Genet A. 2012;158A:664–668.

Scott

Smith

. Moyamoya disease and moyamoya syndrome. N Engl J Med. 2009;360:1226–1237.