High-resolution iris and retinal imaging in multisystemic smooth muscle dysfunction syndrome due to a novel Asn117Lys substitution in ACTA2: a case report

Autor: Kyle S. Yau, Aisling B. Mc Glacken-Byrne, Philip Tuch, Mark R. Davis, Fred K. Chen, Nigel G. Laing, Padma Sivadorai, Danial Roshandel, David Prentice, Michael R. Brown
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Pathology
Vascular smooth muscle
Choreiform movement
Iris
Case Report
Muscle
Smooth
Vascular
chemistry.chemical_compound
0302 clinical medicine
lcsh:Ophthalmology
Fluorescein Angiography
Ductus Arteriosus
Patent
biology
Mydriasis
Eye Diseases
Hereditary
General Medicine
Magnetic Resonance Imaging
medicine.anatomical_structure
Congenital mydriasis
Female
ACTA2
OCTA
Tomography
Optical Coherence
Adult
medicine.medical_specialty
Retinal Artery
Iris sphincter muscle
Mutation
Missense
03 medical and health sciences
Muscular Diseases
Retinal Diseases
medicine
Retinal arteriolar tortuosity
Humans
MSMDS
Aged
business.industry
Retinal
Muscle
Smooth
medicine.disease
Actins
Retinal artery tortuosity
Ophthalmology
Stenosis
Cerebrovascular Disorders
chemistry
Amino Acid Substitution
lcsh:RE1-994
030221 ophthalmology & optometry
biology.protein
Sphincter
business
Adaptive optics
030217 neurology & neurosurgery
Zdroj: BMC Ophthalmology
BMC Ophthalmology, Vol 20, Iss 1, Pp 1-8 (2020)
ISSN: 1471-2415
Popis: Background Congenital mydriasis and retinal arteriolar tortuosity are associated with the life-threatening multisystemic smooth muscle dysfunction syndrome (MSMDS) due to mutations in the gene, ACTA2, which encodes alpha-smooth muscle actin (α-SMA). Previous reports attributed MSMDS-related congenital mydriasis to the absence of iris sphincter muscle. Similarly, it has been hypothesized that abnormal proliferation of the vascular smooth muscle cells causes the marked tortuosity of retinal arterioles in MSMDS. In this report, high-resolution ocular imaging reveals unexpected findings that reject previous hypotheses. Case presentation The proband is a 37-year-old female with a history of neonatal patent ductus arteriosus (PDA) ligation, left-sided choreiform movements at the age of 11 and a transient aphasia with right-sided weakness at the age of 30. Her older sister also had PDA ligation and congenital mydriasis but no neurological deficit up to age 41. Magnetic resonance angiogram demonstrated cerebrovascular lesions resembling but distinct from Moyamoya disease, characterised by internal carotid artery dilatation, terminal segment stenosis and absent basal collaterals. Their mother had poorly reactive pupils with asymptomatic cerebral arteriopathy resembling her daughters. All three had prominent retinal arteriolar tortuosity. The daughters were heterozygous and the mother was a somatic mosaic for a novel c.351C > G (p.Asn117Lys) transversion in ACTA2. Iris optical coherence tomography (OCT) showed a hyporeflective band anterior to the pigment epithelium indicating the presence of dysfunctional sphincter muscle. Adaptive optics retinal imaging showed no thickening of the arteriolar vessel wall whilst OCT angiography showed extreme corkscrew course of arterioles suggesting vessel elongation. Conclusions In addition to the known association between Met46, Arg179 and Arg258 substitutions and ACTA2-related arteriopathy, this case illustrates the possibility that Asn117 also plays an important role in α-SMA function within the cerebrovascular smooth muscle cell. MSMDS-related congenital mydriasis is due to reduced iris sphincter contractility rather than its absence. Retinal arteriolar tortuosity might be due to longitudinal proliferation of arteriolar smooth muscle cells. The described cerebrovascular and ocular signs are consistent with predicted effects of the novel Asn117Lys substitution in ACTA2.
Databáze: OpenAIRE
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