EXPLANATION


Smooth muscle is located throughout the body and has numerous physiologic functions. Contraction depends on the interaction of myosin thick filaments and actin thin filaments, which are encoded on the ACTA2 gene on chromosome 10. Mutations in ACTA2 have been associated with various smooth muscle disease phenotypes, with a specific de novo mutation of arginine residue 179 (R179) resulting in Multi System Smooth Muscle Dysfunction Syndrome (MSMDS). This disease was first described in 2010, and it is rare with less than 100 known cases worldwide. However, an increasing incidence can be attributed to improved recognition of the clinical manifestations and enhanced genetic testing.


The clinical manifestations of MSMDS are heterogeneous, but include congenital mydriasis, presence of a patent ductus arteriosus (PDA), pulmonary arterial hypertension, vascular aneurysms, Moyamoya-type cerebrovascular disease, internal carotid artery ectasia, intestinal hypoperistalsis and malrotation, cholelithiasis, prune belly syndrome, and hypotonic bladder. Signs and symptoms typically manifest at birth or in early childhood. The diagnosis is based on clinical suspicion, often triggered by conspicuously dilated pupils or other clinical characteristics and is confirmed by genetic testing. Current treatment is based on clinical manifestations, and requires a multi-disciplinary approach usually involving neurology, cardiology, ophthalmology, and urology. Research is currently being conducted into gene therapy as a curative measure.


These patients often require frequent hospitalization, procedures, and surveillance imaging including echocardiography and magnetic resonance imaging (MRI). Common procedures in these patients include PDA ligation, gastrointestinal and urological surgery, and bronchoscopy. This makes it pertinent for pediatric anesthesiologists to be aware of the anesthetic implications of this disease to mitigate periprocedural risk. Patients with MSMDS have dysfunctional autoregulation in blood pressure and are prone to hypotension, which can be profound when exposed to anesthetic agents with negative effects on systemic vascular resistance. Baseline diastolic hypotension is common and non-invasive blood pressure measurements are often inaccurate. A recent case series by Houska et al. showed that 40% of anesthetics in children with MSMDS required vasopressor administration to maintain a safe blood pressure. Given that these patients also have cerebrovascular disease that is like Moyamoya and carotid artery ectasia, the most serious complication of MSMDS is stroke. Most of these patients demonstrate white matter and chronic ischemic changes on MRI of the brain at an early age. The combination of a cerebrovascular disease and the inability to autoregulate blood pressure makes these children at high risk for anesthetic complications with large changes in blood pressure. Maintenance of blood pressure and cerebral perfusion should be the primary goal for the provider caring for these children.


The correct answer is A. Patients with MSMDS are at elevated risk for cerebrovascular accidents, particularly when exposed to drugs that reduce systemic vascular resistance. There has been no published literature suggesting an increased incidence of malignant hyperthermia or difficult intubation in patients MSMDS.


REFERENCES


Houska N, Schafer M, Chatfield KC, Bernard TJ, Ing RJ. Anesthetic considerations for children with multisystem smooth muscle dysfunction syndrome and review of the literature. J Cardiothorac Vasc Anesth. 2022;36(8 Pt B):3205-3211.


Milewicz DM, Østergaard JR, Ala-Kokko LM, et al. De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction. Am J Med Genet A. 2010;152A(10): 2437-2443.


Regalado ES, 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):1206-1215.