Cerebral arteriopathy associated with heterozygous Arg179Cys mutation in the ACTA2 gene: Report in 2 newborn siblings

Grazia, José de; Delgado, Ignacio; Sánchez‐Montáñez, Ángel; Boronat, Susana; Campo, Miguel del; Vázquez, Élida

doi:10.1016/j.braindev.2016.08.003

Cited by 14 publications

(12 citation statements)

References 9 publications

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“…Cerebrovascular disease, including stenosis or hypoplasia of arteries and white matter changes, are present as early as the neonatal period in this study and previous reports 3 , 7 , 8 , 21 . Patients have a high risk of vaso-occlusive strokes and seizures, the majority of which were observed in neonates and young children.…”

Section: Discussionsupporting

confidence: 83%

Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations

Regalado

Mellor‐Crummey

Backer

et al. 2018

Genetics in Medicine

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PURPOSESmooth muscle dysfunction syndrome (SMDS) due to heterozygous ACTA2 arginine 179 alterations is characterized by patent ductus arteriosus, vasculopathy (aneurysm and occlusive lesions), pulmonary arterial hypertension, and other complications in smooth muscle-dependent organs. We sought to define the clinical history of SMDS to develop recommendations for evaluation and management.METHODSMedical records of 33 patients with SMDS (median age 12 years) were abstracted and analyzed.RESULTSAll patients had congenital mydriasis and related pupillary abnormalites at birth and presented in infancy with a patent ductus arteriosus or aorto-pulmonary window. Patients had cerebrovascular disease characterized by small vessel disease (hyperintense periventricular white matter lesions; 95%), intracranial artery stenosis (77%), ischemic strokes (27%), and seizures (18%). Twelve (36%) patients had thoracic aortic aneurysm repair or dissection at median age of 14 years and aortic disease was fully penetrant by the age of 25 years. Three (9%) patients had axillary artery aneurysms complicated by thromboembolic episodes. Nine patients died between the ages of 0.5 and 32 years due to aortic, pulmonary or stroke complications, or unknown causes.CONCLUSIONBased on these data, recommendations are provided for the surveillance and management of SMDS to help prevent early onset life-threatening complications.

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Section: Discussionsupporting

confidence: 83%

Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations

Regalado

Mellor‐Crummey

Backer

et al. 2018

Genetics in Medicine

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“…Indeed, 3 of the 4 reported cases with this mutation demonstrated some degree of irregular brain development [7,15]. For example, Meuwissen et al [7] reported a 2-year-old female with ACTA2 Arg179Cys; her MRI revealed a dysplastic corpus callosum with a small genu and an absent rostrum and lamina terminalis.…”

Section: Clinical Significancementioning

confidence: 99%

“…The cingulate gyrus was abnormally positioned and sulcation of the medial cerebral hemispheres was abnormal, resulting in anomalous anatomy of the frontal lobes. de Grazia et al [15] described the first case of newborn siblings with MSMDS who, coincidentally, had the ACTA2 Arg179Cys mutation and significant DOI: 10.1159/000493863 brain anomalies. Of note, both parents' DNA tested negative for ACTA2 mutations indicating mutation genesis was due to germ line mosaicism in both siblings.…”

Section: Clinical Significancementioning

confidence: 99%

<b><i>ACTA2</i></b> Cerebral Arteriopathy: Not Just a Puff of Smoke

et al. 2018

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Background: Missense mutations in the gene that codes for smooth muscle actin, ACTA2, cause diffuse smooth muscle dysfunction and a distinct cerebral arteriopathy collectively known as multisystemic smooth muscle dysfunction syndrome (MSMDS). Until recently, ACTA2 cerebral arteriopathy was considered to be a variant of moyamoya disease. However, recent basic science and clinical data have demonstrated that the cerebral arteriopathy caused by mutant ACTA2 exhibits genetic loci, histopathology, neurological sequelae, and radiographic findings unique from moyamoya disease. We conducted a literature review to provide insight into the history, clinical significance, and neurosurgical management of this recently described novel cerebral arteriopathy. Summary: We performed a literature search using PubMed with the key words “ACTA2 mutation,” “ACTA2 cerebral arteriopathy,” and “multisystemic smooth muscle dysfunction syndrome.” Case reports with confirmed ACTA2 mutations and cerebral arteriopathy were included in our review. Our literature search revealed 15 articles (58 cases) of confirmed ACTA2 cerebral arteriopathy. Distinctive features of this arteriopathy included an aberrant internal carotid circulation with dilatation of the proximal segments, occlusive disease at the distal segments, and dolichoectasia. As such, mutant ACTA2 predisposed patients to ischemic strokes as children. Direct and indirect cerebral revascularization procedures are the mainstay treatment options with varying degrees of success. Key Messages: ACTA2 cerebral arteriopathy is a recently described novel cerebrovascular disease seen in patients with MSMDS. Patients currently diagnosed with moyamoya disease who also have dysfunction of smooth muscle organs may benefit from reevaluation by a medical geneticist and ACTA2 genotyping.

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“…The most severe form is ACTA2 Arg179His. The discovery of this mutation has been invariably associated with a high risk of infant mortality and poor prognosis[6]. Here, we report one Chinese infant with MSMDS with a heterozygous ACTA2 Arg179His substitution who presented with patent foramen ovale, congenital nonreactive mydriasis, dyspnea, development delay, and abnormal signals in magnetic resonance imaging (MRI) of the brain.…”

Section: Introductionmentioning

confidence: 99%

“…Other rare mutations are Arg179Cys and Arg179Leu[2,4-7]. The Arg179His substitution is associated with the neurovascular phenotype, while the Arg179Cys mutation is especially related to brain development[6]. The most severe form is ACTA2 Arg179His.…”

Section: Introductionmentioning

confidence: 99%

Multisystem smooth muscle dysfunction syndrome in a Chinese girl: A case report and review of the literature

Chen¹,

Wang²,

Hao³

et al. 2019

WJCC

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BACKGROUNDMultisystemic smooth muscle dysfunction syndrome (MSMDS) is a rare genetic disease worldwide. The main mutation is the actin alpha 2 (ACTA2) gene p.R179H. In this paper, we report a Chinese MSMDS patient and systematically review the previous literature.CASE SUMMARYHere, we report a 9.6-month-old Chinese girl who was diagnosed with MSMDS based on her history and symptoms, such as recurrent cough, wheezing, and complications with congenital fixed dilated pupils. Chest high-resolution computed tomography revealed inhomogeneous lung transparency, obvious exudative lesions, and some lung fissures that were markedly thickened. Cranial magnetic resonance imaging excluded bleeding and infarction but showed abnormal signals in the centrum ovale majus and bilateral periventricular regions. Echocardiography only showed patent foramen ovale, and no patent ductus arteriosus, pulmonary artery dilatation, or pulmonary hypertension was found. Bronchoscopy indicated moderate bronchial malacia. These examinations in conjunction with the typical eye abnormality suggested a diagnosis of MSMDS, and sequencing of exon 6 of the ACTA2 gene demonstrated the heterozygous mutation c.536G>A, p.R179H. However, her parents’ gene analyses were normal.CONCLUSIONMSMDS is a rare genetic disease mainly caused by the mutation of the ACTA2 gene p.R179H. Early genetic diagnosis should be performed for children presenting with congenital fixed dilated pupils and patent ductus arteriosus. During the process of diagnosis and treatment, clinicians should be on high alert for cerebrovascular, cardiovascular, and pulmonary complications.

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Cerebral arteriopathy associated with heterozygous Arg179Cys mutation in the ACTA2 gene: Report in 2 newborn siblings

Cited by 14 publications

References 9 publications

Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations

Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations

<b><i>ACTA2</i></b> Cerebral Arteriopathy: Not Just a Puff of Smoke

Multisystem smooth muscle dysfunction syndrome in a Chinese girl: A case report and review of the literature

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