Multisystemic smooth muscle dysfunction syndrome
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Multisystemic smooth muscle dysfunction syndrome is a rare genetic disorder caused by mutations in the ACTA2 gene, resulting in intracranial steno-occlusive disease and aortic dissection or aneurysm, among other complications.
Most cases are diagnosed in childhood 1.
There are a large number of potential clinical manifestations:
- ocular abnormalities
- mydriasis (85%)
- hypoplastic or absent iris (aniridia) (21%)
- retinal vessel tortuosity (35%)
- aortic disease
- cerebrovascular disease
- ischemic strokes (27%)
- seizures (18%)
- lung disease
- peripheral arterial aneurysm (54%)
- gastrointestinal abnormalities
- genitourinary abnormalities
The syndrome is characterized by smooth muscle dysfunction in multiple organs, resulting in various manifestations 1, as aforementioned.
Most published cases have de novo mutations, but the inheritance would be autosomal dominant. Heterozygous mutations in the ACTA2 gene on chromosome 10q23 result in the substitution of the arginine-179 codon for another amino acid, most commonly histidine (Arg179His) 1.
Vascular imaging is indicated in patients initially diagnosed with smooth muscle dysfunction syndrome to evaluate the thoracic aorta, upper extremity arteries, and cerebrovascular system. Additionally, brain MRI is indicated to evaluate the brain parenchyma.
Brain MRI shows characteristic malformations in affected individuals 2:
- V-shaped bending (on axial images) of the anterior corpus callosum
- absence of anterior cingulate gyri
- abnormally radially oriented frontal lobe gyration
- dysgyria with a peri-Sylvian and frontal predominance 4
- midbrain: dysmorphic with an appearance of being squeezed in the transverse dimension
- pons: flattened in the midline to create the "twin peaks sign" (on axial images) and indented multiple times on the ventral surface (on sagittal images)
In addition to the above, brain MRI reveals the common sequelae of periventricular white matter T2/FLAIR hyperintensities (in 95%) and infarctions (in 27%).
MRA of the head and neck shows a characteristic arteriopathy 2:
- proximal internal carotid artery dilation
- stenosis or occlusion of the intracranial internal carotid arteries (in 77%), without moyamoya-like collaterals
- "broomstick appearance" (straightened configuration) of the cerebral arteries 3
- 1. Regalado E, Mellor-Crummey L, De Backer J et al. Clinical History and Management Recommendations of the Smooth Muscle Dysfunction Syndrome Due to ACTA2 Arginine 179 Alterations. Genet Med. 2018;20(10):1206-15. doi:10.1038/gim.2017.245 - Pubmed
- 2. D'Arco F, Alves C, Raybaud C et al. Expanding the Distinctive Neuroimaging Phenotype of ACTA2 Mutations. AJNR Am J Neuroradiol. 2018;39(11):2126-31. doi:10.3174/ajnr.a5823 - Pubmed
- 3. Sabo T, Stokes M, Karbhari N, Veltkamp D, Pfeifer C. ACTA2 Leukovasculopathy: A Rare Pediatric White Matter Disorder. Radiology Case Reports. 2020;15(8):1285-8. doi:10.1016/j.radcr.2020.05.031 - Pubmed
- 4. Subramanian S, Biswas A, Alves C et al. ACTA2-Related Dysgyria: An Under-Recognized Malformation of Cortical Development. AJNR Am J Neuroradiol. 2021;43(1):146-50. doi:10.3174/ajnr.a7364 - Pubmed