Anesthetic Considerations for Children With Multisystem Smooth Muscle Dysfunction Syndrome and Review of the Literature

Abstract

EFFECTIVE CONTRACTION OF SMOOTH MUSCLE is dependent on the interaction of myosin thick filaments and actin thin filaments, in particular smooth muscle α-actin, which is encoded by the ACTA2 gene on chromosome 10 (10q23.31). 1 Guo DC Pannu H Tran-Fadulu V et al. Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections. Nat Genet. 2007; 39: 1488-1493 Crossref PubMed Scopus (638) Google Scholar Mutations in ACTA2 are known to be associated with familial aortic aneurysm and dissections, coronary artery disease, moyamoya disease, iris flocculi, and cutaneous levido reticularis. 2 Guo DC Papke CL Tran-Fadulu V et al. Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease. Am J Hum Genet. 2009; 84: 617-627 Abstract Full Text Full Text PDF PubMed Scopus (377) Google Scholar A specific recurrent de novo mutation in ACTA2 can occur in Arginine residue 179 (R179), which results in a more severe multisystem smooth muscle dysfunction syndrome (MSMDS, MIM 613834). 3 Milewicz DM Ostergaard 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: 2437-2443 Crossref PubMed Scopus (189) Google Scholar First reported in 2010, this syndrome usually is clinically diagnosed in children who present with congenital mydriasis, patent ductus arteriosus (PDA) or aortopulmonary window, pulmonary arterial hypertension, aortic and other vascular aneurysms, Moyamoya-type cerebrovascular disease, internal carotid artery ectasia, intestinal hypoperistalsis and malrotation, cholelithiasis, and hypotonic bladder. 3 Milewicz DM Ostergaard 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: 2437-2443 Crossref PubMed Scopus (189) Google Scholar , 4 Ades LC Davies R Haan EA et al. Aortic dissection, patent ductus arteriosus, iris hypoplasia and brachytelephalangy in a male adolescent. Clin Dysmorphol. 1999; 8: 269-276 PubMed Google Scholar , 5 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: 1206-1215 Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar Figure 1 illustrates the typical cerebrovascular findings of magnetic resonance angiography in patients with MSMDS. Table 1 illustrates some of the systemic manifestations of MSMDS. Although the prevalence of MSMDS is still to be determined, given how recently the causal gene has been discovered, a recent review by Chen et al found only 32 cases reported in the literature from 2010 to 2019, indicating that the prevalence is likely well below 1:1,000,000. 6 Chen SN Wang YQ Hao CL et al. Multisystem smooth muscle dysfunction syndrome in a Chinese girl: A case report and review of the literature. World J Clin Cases. 2019; 7: 4355-4365 Crossref PubMed Scopus (6) Google Scholar Although significantly rare, given the identifying constellation of symptoms and increase in genetic testing capability, an increase in the number of children diagnosed with MSMDS is anticipated. 3 Milewicz DM Ostergaard 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: 2437-2443 Crossref PubMed Scopus (189) Google Scholar Table 1Reported Clinical Manifestation MSMDS With Their Anesthetic Implications Systemic Manifestations of MSMDS Anesthetic implications Neurological Cerebral arteriopathy Moyamoya disease, cerebrovascular accident Periventricular/white matter abnormalities Developmental delay Seizure disorder Medications interactions with anesthetic drugs Ophthalmic Congenital mydriasis Fixed, dilated pupils, concerning if not recognized before anesthesia Cardiovascular Vascular smooth muscle dysfunction Hypotension, increased response to vasodilator effects of anesthetics Attenuated response to vasopressors, low baseline diastolic blood pressure Aortic aneurysm Risk for rupture, airway compression, dissection Patent ductus arteriosus Pulmonary Hypertension, aneurysmal, increased bleeding during surgery Coronary artery disease/AP window Risk for myocardial ischemia Pulmonary Obstructive sleep apnea Airway obstruction, hypoventilation, consider decreased opioid use Airway malacia Airway obstruction during induction and emergence, difficult intubation Pulmonary vascular disease Pulmonary hypertension, consider medications and perioperative sue of nitric oxide if severe disease is present. Chronic lung disease Reactive airway, bronchospasm Gastrointestinal Intestinal malrotation Risk for bowel obstruction Hypoperistalsis Risk for aspiration Cholelithiasis prune belly Genitourinary Hypotonic bladder Recurrent urinary tract infections VUR Reproductive Cryptorchidism Testicular torsion Atonic uterus Increased risk for postpartum hemorrhage Modified from Guo et al and Milewicz et al.2,3 Abbreviations: AP, aortopulmonary window; MSMDS, multisystem smooth muscle dysfunction syndrome; VUR, vesicoureteral reflux. Open table in a new tab Modified from Guo et al and Milewicz et al.2,3 Abbreviations: AP, aortopulmonary window; MSMDS, multisystem smooth muscle dysfunction syndrome; VUR, vesicoureteral reflux.