{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T11:42:24Z","timestamp":1776080544951,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T00:00:00Z","timestamp":1775952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Infantile cardiomyopathy is a rare but often life-threatening condition in which monogenic causes are particularly relevant, especially when cardiac disease is preceded by hypotonia or multisystem involvement. Among sarcomeric genes, MYL2, encoding the ventricular regulatory myosin light chain, plays a critical role in myocardial contractility. However, biallelic MYL2-associated disease remains exceptionally rare, and its clinical spectrum is not fully defined. This study aims to describe a novel case and further delineate the phenotype of recessive MYL2-related cardiomyopathy. Methods: We report a male infant with congenital hypotonia and delayed motor development who underwent extensive metabolic, neuromuscular, and neuroimaging evaluation. Trio-based whole-exome sequencing was performed to identify a potential genetic etiology, followed by variant interpretation using standard bioinformatic and ACMG\/AMP criteria. Results: The patient developed acute decompensated heart failure at approximately 10 months of age, with severe left ventricular systolic dysfunction and multiorgan failure, and died at 12 months despite maximal intensive care support. Whole-exome sequencing identified a homozygous MYL2 c.413T&gt;A (p.Met138Lys) missense variant. The variant is absent or extremely rare in population databases, affects a highly conserved residue, is predicted to be deleterious by multiple in silico tools, and is compatible with autosomal recessive inheritance, with both parents confirmed as heterozygous carriers. In the context of a phenotype consistent with recessive MYL2-associated disease, these findings support a likely pathogenic interpretation. Conclusions: This case expands the allelic and phenotypic spectrum of recessive MYL2-associated cardiomyopathy and highlights the value of early genomic testing in infants with unexplained hypotonia and rapidly progressive cardiac dysfunction. Molecular diagnosis may aid in prognosis, clinical decision-making, and genetic counseling.<\/jats:p>","DOI":"10.3390\/genes17040441","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T10:19:14Z","timestamp":1776075554000},"page":"441","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fatal Infantile Cardiomyopathy Associated with a Homozygous MYL2 c.413T&gt;A (p.Met138Lys) Variant: A Case Expanding the Recessive MYL2 Phenotypic Spectrum"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7372-4796","authenticated-orcid":false,"given":"Mohammed Shahab","family":"Uddin","sequence":"first","affiliation":[{"name":"Department of Pediatric, Ministry of National Guard Health Affairs, Dammam 31412, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center, Riyadh 11481, Saudi Arabia"},{"name":"Faculty of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11426, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasmeen","family":"Alnamshan","sequence":"additional","affiliation":[{"name":"Department of Pediatric, Ministry of National Guard Health Affairs, Dammam 31412, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center, Riyadh 11481, Saudi Arabia"},{"name":"Faculty of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11426, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6784-8067","authenticated-orcid":false,"given":"Khaled","family":"Shafeen","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Semmelweis University, 1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syeda Nilofer","family":"Jahan","sequence":"additional","affiliation":[{"name":"Department of Pediatric, Ministry of National Guard Health Affairs, Dammam 31412, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center, Riyadh 11481, Saudi Arabia"},{"name":"Faculty of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11426, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora","family":"AlMadhi","sequence":"additional","affiliation":[{"name":"Department of Pediatric, Ministry of National Guard Health Affairs, Dammam 31412, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center, Riyadh 11481, Saudi Arabia"},{"name":"Faculty of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11426, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karthiga","family":"Gurumurthy","sequence":"additional","affiliation":[{"name":"Department of Pediatric, Ministry of National Guard Health Affairs, Dammam 31412, Saudi Arabia"},{"name":"Saveetha College of Nursing, Seveetha Institute of Medical and Technical Sciences, Chennai 602105, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7140-2449","authenticated-orcid":false,"given":"Abdullah Bin","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Pediatric, Ministry of National Guard Health Affairs, Dammam 31412, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center, Riyadh 11481, Saudi Arabia"},{"name":"Faculty of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11426, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amr","family":"Esmail","sequence":"additional","affiliation":[{"name":"Department of Pediatric, Ministry of National Guard Health Affairs, Dammam 31412, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center, Riyadh 11481, Saudi Arabia"},{"name":"Faculty of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11426, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryam","family":"AlQannas","sequence":"additional","affiliation":[{"name":"Department of Pediatric, Ministry of National Guard Health Affairs, Dammam 31412, Saudi Arabia"},{"name":"King Abdullah International Medical Research Center, Riyadh 11481, Saudi Arabia"},{"name":"Faculty of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11426, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1001\/jama.296.15.1867","article-title":"Incidence, causes, and outcomes of dilated cardiomyopathy in children","volume":"296","author":"Towbin","year":"2006","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1056\/NEJMoa021715","article-title":"The incidence of pediatric cardiomyopathy in two 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