Eye features in three Danish patients with multisystemic smooth muscle dysfunction syndrome

Møller, Hans Ulrik; Fledelius, Hans C.; Milewicz, Dianna M.; Regalado, Ellen S.; Østergaard, John R.

doi:10.1136/bjophthalmol-2011-301462

Cited by 34 publications

(40 citation statements)

References 15 publications

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“…Indeed, neurosurgical revascularization for moyamoya disease demonstrates a significant protective effect in preventing the recurrence of stroke; however, a similar reduction in the incidence of future stroke with revascularization is not observed in ACTA2 cerebral arteriopathy patients [4,31]. Moller et al [3] described a 6-year-old who underwent a 2-step bilateral bypass revascularization procedure, which was complicated by significant right hemispheric ischemic infarction. A second patient reported by Moller et al [3] was a 4-year-old who underwent bilateral bypass for a previous right hemispheric infarction.…”

Section: Neurosurgical Managementmentioning

confidence: 99%

“…Moller et al [3] described a 6-year-old who underwent a 2-step bilateral bypass revascularization procedure, which was complicated by significant right hemispheric ischemic infarction. A second patient reported by Moller et al [3] was a 4-year-old who underwent bilateral bypass for a previous right hemispheric infarction. The patient made a full recovery.…”

Section: Neurosurgical Managementmentioning

confidence: 99%

“…Until recently, cerebral arteriopathy associated with MSMDS was considered to be a variant of moyamoya disease [2][3][4]. However, ACTA2 cerebral arteriopathy is now classified as a novel cerebrovascular disease with unique genetic loci, histopathologic findings, and cerebrovascular features.…”

Section: Introductionmentioning

confidence: 99%

“…However, ACTA2 cerebral arteriopathy is now classified as a novel cerebrovascular disease with unique genetic loci, histopathologic findings, and cerebrovascular features. To date, only 58 cases of MSMDS with ACTA2 cerebral arteriopathy have been reported and confirmed via genotyping [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16]. Here, we provide a literature review of ACTA2 cerebral arteriopathy encompassing the history of the disease from first observation to new classification, clinical significance and neurosurgical management strategies.…”

Section: Introductionmentioning

confidence: 99%

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ACTA2 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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Section: Neurosurgical Managementmentioning

confidence: 99%

Section: Neurosurgical Managementmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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ACTA2 Cerebral Arteriopathy: Not Just a Puff of Smoke

et al. 2018

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“…Recently a multisystemic smooth muscle dysfunction syndrome resulting from a mutation in ACTA2 (p.R179H) characterised by congenital fixed dilated pupils with loss of accommodation, persistent ductus arteriosus, pulmonary hypertension, aortic and cerebrovascular disease and hypotonic bladder and bowel was reported. 9 In conclusion, iris flocculi and congenital mydrasis should alert ophthalmologists to the possibility of ACTA2 mutations and should prompt further investigation for life-threatening cardiovascular associations.…”

mentioning

confidence: 99%

Iris Flocculi as an Ocular Marker ofACTA2Mutation in Familial Thoracic Aortic Aneurysms and Dissections

Chamney

McGimpsey

McConnell

et al. 2013

Ophthalmic Genetics

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ACTA2 mutation with childhood cardiovascular, autonomic and brain anomalies and severe outcome

Meuwissen

Lequin

Heus

et al. 2013

American J of Med Genetics Pt A

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Thoracic aortic aneurysm and dissection (TAAD) are associated with connective tissue disorders like Marfan syndrome and Loeys-Dietz syndrome, caused by mutations in the fibrillin-1, the TGFβ-receptor 1- and -2 genes, the SMAD3 and TGFβ2 genes, but have also been ascribed to ACTA2 gene mutations in adults, spread throughout the gene. We report on a novel de novo c.535C>T in exon 6 leading to p.R179C aminoacid substitution in ACTA2 in a toddler girl with primary pulmonary hypertension, persistent ductus arteriosus, extensive cerebral white matter lesions, fixed dilated pupils, intestinal malrotation, and hypotonic bladder. Recently, de novo ACTA2 R179H substitutions have been associated with a similar phenotype and additional cerebral developmental defects including underdeveloped corpus callosum and vermis hypoplasia in a single patient. The patient here shows previously undescribed abnormal lobulation of the frontal lobes and position of the gyrus cinguli and rostral dysplasis of the corpus callosum; she died at the age of 3 years during surgery due to vascular fragility and rupture of the ductus arteriosus. Altogether these observations support a role of ACTA2 in brain development, especially related to the arginine at position 179. Although all previously reported patients with R179H substitution successfully underwent the same surgery at younger ages, the severe outcome of our patient warns against the devastating effects of the R179C substitution on vasculature.

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Eye features in three Danish patients with multisystemic smooth muscle dysfunction syndrome

Cited by 34 publications

References 15 publications

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

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

Iris Flocculi as an Ocular Marker ofACTA2Mutation in Familial Thoracic Aortic Aneurysms and Dissections

ACTA2 mutation with childhood cardiovascular, autonomic and brain anomalies and severe outcome

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