{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:02:49Z","timestamp":1790618569056,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":105,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt C"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Myhre Syndrome (MYHRS, MIM #139210) is a rare, multisystem connective tissue disorder caused by recurrent heterozygous gain\u2010of\u2010function pathogenic variants in the\n                    <jats:italic>SMAD4<\/jats:italic>\n                    gene, a key player in TGF\u2010\u03b2 signaling and a regulator of extracellular matrix homeostasis. MYHRS is characterized by a progressive fibrotic phenotype affecting multiple organ systems, including the skeletal, cardiovascular, respiratory, and integumentary systems. MYHRS individuals often present with short stature, joint contractures, cardiac valve defects, subglottic stenosis, and skin thickening. Neurodevelopmental disorders, including autism spectrum disorder, may also occur. Despite the recurrent mutations, MYHRS individuals have significant phenotypic variability. Treatment for MYHRS is symptomatic, and no disease\u2010modifying therapies are currently available. In this article, we discuss potential future therapies in MYHRS, such as TGF\u2010\u03b2 inhibitors, anti\u2010fibrotic drugs, and gene editing approaches. Furthermore, we discuss unmet needs on clinical and biochemical endpoints that are critical for the investigation of new therapies.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.c.70008","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T08:36:29Z","timestamp":1773650189000},"page":"386-391","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Therapy for Myhre Syndrome: Goals, Misconceptions, and Current Agents"],"prefix":"10.1002","volume":"199","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1569-1556","authenticated-orcid":false,"given":"Alessandro","family":"De Falco","sequence":"first","affiliation":[{"name":"Department of Translational Medical Sciences University of Naples Federico II  Naples Italy"},{"name":"Telethon Institute of Genetics and Medicine (TIGEM)  Pozzuoli Italy"},{"name":"Scuola Superiore Meridionale (SSM, School of Advanced Studies), Genomics and 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