{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T17:08:43Z","timestamp":1770916123390,"version":"3.50.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T00:00:00Z","timestamp":1736380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Multisystemic smooth muscle dysfunction syndrome (MSMDS) is an autosomal dominant disorder caused by mutations in the <jats:italic>ACTA2<\/jats:italic> gene, resulting in variable clinical manifestation and multi-organ dysfunction. Interstitial lung disease (ILD) is a rare phenotype of this condition. We describe a rare infant case of an 8-month-old boy who presented with progressively worsening dyspnea, along with intermittent episodes of respiratory distress and cyanosis since birth. A chest CT scan revealed typical signs of ILD. Additionally, the patient exhibited congenital mydriasis, aortic coarctation, PDA, and pulmonary hypertension. Whole-exome sequencing identified a <jats:italic>de novo<\/jats:italic> variant c.536G &amp;gt; A (p.Arg179His) in the <jats:italic>ACTA2<\/jats:italic> gene. These findings confirmed the diagnosis of MSMDS. Despite intensive hospital-based pulmonary care and optimized therapy, the child passed away due to sudden cardiac and respiratory arrest on the 12th day of hospitalization. This case underscores the importance of considering MSMDS in the differential diagnosis of infantile ILD.<\/jats:p>","DOI":"10.3389\/fphar.2024.1510969","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T06:11:35Z","timestamp":1736403095000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Case report: Multisystemic smooth muscle dysfunction syndrome: a rare genetic cause of infantile interstitial lung disease"],"prefix":"10.3389","volume":"15","author":[{"given":"Qianying","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidan","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuelin","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"bcr2013010997","DOI":"10.1136\/bcr-2013-010997","article-title":"Cerebral arteriopathy associated with Arg179His ACTA2 mutation","volume":"2013","author":"Amans","year":"2013","journal-title":"BMJ Case Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e46","DOI":"10.1136\/neurintsurg-2013-010997.rep","article-title":"Cerebral arteriopathy associated with Arg179His ACTA2 mutation","volume":"6","author":"Amans","year":"2014","journal-title":"J. Neurointerv Surg."},{"key":"B3","doi-asserted-by":"publisher","first-page":"NP498","DOI":"10.1177\/2150135120902120","article-title":"Aneurysmal dilatation of ductus arteriosus and pulmonary artery in association with ACTA2 mutation","volume":"11","author":"Ardhanari","year":"2020","journal-title":"World J. Pediatr. Congenit. Heart Surg."},{"key":"B4","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.jaapos.2014.02.010","article-title":"Congenital mydriasis and prune belly syndrome in a child with an ACTA2 mutation","volume":"18","author":"Brodsky","year":"2014","journal-title":"J. AAPOS"},{"key":"B5","doi-asserted-by":"publisher","first-page":"4355","DOI":"10.12998\/wjcc.v7.i24.4355","article-title":"Multisystem smooth muscle dysfunction syndrome in a Chinese girl: a case report and review of the literature","volume":"7","author":"Chen","year":"2019","journal-title":"World J. Clin. Cases"},{"key":"B6","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.braindev.2016.08.003","article-title":"Cerebral arteriopathy associated with heterozygous Arg179Cys mutation in the ACTA2 gene: report in 2 newborn siblings associated with heterozygous Arg179Cys mutation in the ACTA2 gene: report in 2 newborn siblings","volume":"39","author":"de Grazia","year":"2017","journal-title":"Brain Dev."},{"key":"B7","doi-asserted-by":"publisher","first-page":"3205","DOI":"10.1053\/j.jvca.2022.04.019","article-title":"Anesthetic considerations for children with multisystem smooth muscle dysfunction syndrome and review of the literature","volume":"36","author":"Houska","year":"2022","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"B8","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1016\/j.braindev.2020.12.001","article-title":"Refractory cerebral infarction in a child with an ACTA2 mutation","volume":"43","author":"Kanamori","year":"2021","journal-title":"Brain Dev."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2389","DOI":"10.1002\/ajmg.a.62775","article-title":"Expanding ACTA2 genotypes with corresponding phenotypes overlapping with smooth muscle dysfunction syndrome","volume":"188","author":"Kaw","year":"2022","journal-title":"Am. J. Med. Genet. A"},{"key":"B10","doi-asserted-by":"publisher","first-page":"57","DOI":"10.4137\/CCRPM.S23282","article-title":"Interstitial lung disease in childhood: clinical and genetic aspects","volume":"9","author":"Kitazawa","year":"2015","journal-title":"Clin. Med. Insights Circ. Respir. Pulm. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e166497","DOI":"10.1172\/JCI166497","article-title":"A seed sequence variant in miR-145-5p causes multisystem smooth muscle dysfunction syndrome","volume":"133","author":"Lino Cardenas","year":"2023","journal-title":"J. Clin. Invest"},{"key":"B12","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1002\/ajmg.a.38102","article-title":"Two patients with the heterozygous R189H mutation in ACTA2 and Complex congenital heart defects expands the cardiac phenotype of multisystemic smooth muscle dysfunction syndrome","volume":"173","author":"Logeswaran","year":"2017","journal-title":"Am. J. Med. Genet. A"},{"key":"B13","doi-asserted-by":"publisher","first-page":"21729","DOI":"10.1074\/jbc.M116.744011","article-title":"Severe molecular defects exhibited by the R179H mutation in human vascular smooth muscle \u03b1-actin by the R179H mutation in human vascular smooth muscle \u03b1-actin","volume":"291","author":"Lu","year":"2016","journal-title":"J. Biol. Chem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1002\/ajmg.a.63118","article-title":"Neonatal diagnosis of ACTA2-related disease: a case report and review of literature","volume":"191","author":"Lupo","year":"2023","journal-title":"Am. J. Med. Genet. A"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1001\/jama.2024.3669","article-title":"Interstitial lung disease: a review","volume":"331","author":"Maher","year":"2024","journal-title":"JAMA"},{"key":"B16","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s12886-020-01344-w","article-title":"High-resolution iris and retinal imaging in multisystemic smooth muscle dysfunction syndrome due to a novel Asn117Lys substitution in ACTA2: a case report","volume":"20","author":"Mc Glacken-Byrne","year":"2020","journal-title":"BMC Ophthalmol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1376","DOI":"10.1002\/ajmg.a.35858","article-title":"ACTA2 mutation with childhood cardiovascular, autonomic and brain anomalies and severe outcome","author":"Meuwissen","year":"2013","journal-title":"Am. J. Med. Genet. A"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e17","DOI":"10.1016\/j.urology.2022.11.031","article-title":"Megacystis associated with an underlying ACTA2 variant and diagnosis of multisystemic smooth muscle dysfunction syndrome: a case report","volume":"173","author":"Micke","year":"2023","journal-title":"Urology"},{"key":"B19","doi-asserted-by":"publisher","first-page":"2437","DOI":"10.1002\/ajmg.a.33657","article-title":"De novo ACTA2 mutation causes a novel syndrome of multisystemic smooth muscle dysfunction","author":"Milewicz","year":"2010","journal-title":"Am. J. Med. Genet. A"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1136\/bjophthalmol-2011-301462","article-title":"Eye features in three Danish patients with multisystemic smooth muscle dysfunction syndrome patients with multisystemic smooth muscle dysfunction syndrome","volume":"96","author":"Moller","year":"2012","journal-title":"Br. J. Ophthalmol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1177\/0883073812446631","article-title":"Neonatal stroke and progressive leukoencephalopathy in a child with an ACTA2 mutation","volume":"28","author":"Moosa","year":"2013","journal-title":"J. Child. Neurol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"2965","DOI":"10.1002\/ajmg.a.37857","article-title":"Visceral myopathy: clinical and molecular survey of a cohort of seven new patients and state of the art of overlapping phenotypes","volume":"170","author":"Moreno","year":"2016","journal-title":"Am. J. Med. Genet. A"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2506","DOI":"10.1093\/brain\/aws172","article-title":"A novel distinctive cerebrovascular phenotype is associated with heterozygous Arg179 ACTA2 mutations","volume":"135","author":"Munot","year":"2012","journal-title":"Brain"},{"key":"B24","doi-asserted-by":"publisher","first-page":"63","DOI":"10.12809\/hkmj2210382","article-title":"Multisystemic smooth muscle dysfunction syndrome: the first local case report syndrome: the first local case report","volume":"30","author":"Ng","year":"2024","journal-title":"Hong Kong Med. J."},{"key":"B25","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1177\/2150135116658457","article-title":"Extracorporeal life support in multisystem smooth muscle dysfunction syndrome","volume":"8","author":"Prabhu","year":"2017","journal-title":"World J. Pediatr. Congenit. Heart Surg."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1038\/gim.2017.245","article-title":"Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations","volume":"20","author":"Regalado","year":"2018","journal-title":"Genet. Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1002\/ajmg.a.35206","article-title":"R179H mutation in ACTA2 expanding the phenotype to include prune-belly sequence and skin manifestations","author":"Richer","year":"2012","journal-title":"Am. J. Med. Genet. A"},{"key":"B28","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1097\/WNO.0000000000000090","article-title":"Congenital fixed dilated pupils due to ACTA2-multisystemic smooth muscle dysfunction syndrome","volume":"34","author":"Roulez","year":"2014","journal-title":"J. Neuroophthalmol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1007\/s00381-022-05703-4","article-title":"Communicating hydrocephalus and raised intracranial pressure in association with multi-systemic smooth muscle dysfunction syndrome (MSMDS)","volume":"39","author":"Roylance","year":"2023","journal-title":"Childs Nerv. Syst."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e26094","DOI":"10.1097\/MD.0000000000026094","article-title":"Persistent anterior tunica vasculosa lentis in multisystemic smooth muscle dysfunction syndrome: a case report","volume":"100","author":"She","year":"2021","journal-title":"Med. Baltim."},{"key":"B31","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1136\/bjophthalmol-2018-312306","article-title":"Iris anomalies and the incidence of ACTA2 mutation","volume":"103","author":"Taubenslag","year":"2019","journal-title":"Br. J. Ophthalmol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"8789","DOI":"10.12998\/wjcc.v9.i29.8789","article-title":"ACTA2 mutation is responsible for multisystemic smooth muscle dysfunction syndrome with seizures: a case report and review of literature multisystemic smooth muscle dysfunction syndrome with seizures: a case report and review of literature","volume":"9","author":"Yang","year":"2021","journal-title":"World J. Clin. Cases"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e262","DOI":"10.1542\/peds.2014-3032","article-title":"Progressive aortic dilation associated with ACTA2 mutations presenting in infancy","volume":"136","author":"Yetman","year":"2015","journal-title":"Pediatrics"},{"key":"B34","doi-asserted-by":"publisher","first-page":"e23480","DOI":"10.1002\/jcla.23480","article-title":"Molecular diagnostic in fetuses with isolated congenital anomalies of the kidney and urinary tract by whole-exome sequencing","volume":"34","author":"Zhou","year":"2020","journal-title":"J. Clin. Lab. Anal."},{"key":"B35","doi-asserted-by":"publisher","first-page":"619","DOI":"10.3760\/cma.j.issn.0578-1310.2017.08.014","article-title":"Multisystemic smooth muscle dysfunction syndrome in children: a case report and literature review","volume":"55","author":"Zhou","year":"2017","journal-title":"Zhonghua Er Ke Za Zhi"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1510969\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T13:40:18Z","timestamp":1736516418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1510969\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,9]]},"references-count":35,"alternative-id":["10.3389\/fphar.2024.1510969"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1510969","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,9]]},"article-number":"1510969"}}