Cerebral arteriopathy associated with ACTA2 mutations
General description
Cerebral arteriopathy associated with ACTA2 mutations represents a distinct form of non-atherosclerotic cerebrovascular disease that differs significantly from classical moyamoya disease. ACTA2 mutations cause multisystemic smooth muscle dysfunction syndrome (MSMDS), which affects various organ systems dependent on smooth muscle function. The cerebrovascular manifestations of ACTA2 mutations have only recently been characterized as a separate entity, distinct from Moyamoya disease despite initial similarities.
Clinical manifestations
ACTA2 mutations cause a constellation of clinical features affecting multiple organ systems. The three hallmark signs include patent ductus arteriosus (PDA) or aortopulmonary window, congenital mydriasis, and white matter changes on brain imaging.
Thoracic aortic disease is fully penetrant by age 25 years, with 36% of patients experiencing aortic events (aneurysm repair or dissection) at a median age of 14 years. Type B dissections occur at significantly younger ages than type A dissections (median age 27 versus 36 years). Peripheral arterial dilation affects 54% of patients, commonly involving the proximal internal carotid, common carotid, brachiocephalic, and subclavian arteries.
Cerebrovascular disease is characterized by small vessel disease with hyperintense periventricular white matter lesions in 95% of patients, intracranial artery stenosis in 77%, ischemic strokes in 27%, and seizures in 18%.
Pulmonary complications include pulmonary arterial hypertension in 48% of patients and chronic lung disease in 33%. Gastrointestinal problems encompass gut malrotation (30%), gastroesophageal reflux (30%), and chronic constipation (37%). Urogenital complications include hypotonic bladder (47%), hydronephrosis (31%), and recurrent urinary tract infections (36%). All patients have pupillary abnormalities, and 35% have retinal vessel tortuosity.
References
- Regalado, Ellen S., et al. "Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations." Genetics in Medicine 20.10 (2018): 1206-1215.
- D'Arco, F., et al. "Expanding the distinctive neuroimaging phenotype of ACTA2 mutations." American Journal of Neuroradiology 39.11 (2018): 2126-2131.
- Meuwissen, Marije EC, et al. "ACTA2 mutation with childhood cardiovascular, autonomic and brain anomalies and severe outcome." American Journal of Medical Genetics Part A 161.6 (2013): 1376-1380.
ICA dilation
The characteristic angiographic features include dilatation of the proximal internal carotid arteries.
Stenosis of terminal ICA
The characteristic angiographic features include occlusion of the terminal internal carotid arteries and basilar artery.
Abnormally straight arteries
The characteristic angiographic features include an abnormally straight course of intracranial arteries, and notably, the absence of basal moyamoya collaterals.
White matter abnormalities
Hyperintense periventricular white matter lesions are present in 95% of patients on T2-weighted or FLAIR sequences.
Corpus callosum deformity
MRI demonstrates atrophy of the anterior corpus callosum and characteristic V-shaped deformity.
Absence of rostrum of the corpus callosum
MRI demonstrates aplasia of the rostrum of the corpus callosum.
Pontine deformity
Multiple indentations in the lateral surface of the pons were demonstrated by imaging studies.