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.
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Epidemiology
Most cases are diagnosed in childhood 1.
Clinical presentation
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
- patent ductus arteriosus (91%) or aortopulmonary window (9%) in infancy
- ascending aortic aneurysm (92%) or aortic dissection (15%) in childhood and young adulthood
- cerebrovascular disease
- ischemic strokes (27%)
- seizures (18%)
- lung disease
- pulmonary arterial hypertension (48%)
- chronic lung disease (33%)
- peripheral arterial aneurysm (54%)
- gastrointestinal abnormalities
- hypoperistalsis/constipation (37%)
- intestinal malrotation (30%)
- gastroesophageal reflux (30%)
- cholelithiasis or gallbladder sludge (30%)
- genitourinary abnormalities
- hypotonic bladder (47%)
- recurrent urinary tract infection (36%)
- hydronephrosis (31%)
- prune belly sequence (17%)
- vesicoureteral reflux (16%)
- undescended testes (50% of males)
- hydrocele (33%)
Pathology
The syndrome is characterized by smooth muscle dysfunction in multiple organs, resulting in various manifestations 1, as aforementioned.
Genetics
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.
Radiographic features
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.
MRI
Brain MRI shows characteristic malformations in affected individuals 2:
- cerebrum:
- 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