{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T02:51:38Z","timestamp":1775098298803,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>In recent years, numerous heterozygous ACAN variants have been identified in individuals with short stature. The phenotypic spectrum includes mild to moderate short stature, advanced to delayed bone age, mild dysmorphic features, brachydactyly and\/or other mild skeletal defects and joint pathology in early adulthood which often requires surgery. However, only one multiexonic <jats:italic>ACAN<\/jats:italic> deletion has been reported to date, in a family with short stature, advanced bone age in childhood and early osteoarthritis and spine deformity in the father. Here, we describe 15 individuals from 6 families with <jats:italic>ACAN<\/jats:italic> deletions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Patients and Measurements<\/jats:title><jats:p>All probands were referred for short stature to paediatric endocrinology and genetic clinics in different European hospitals. After molecular studies detected the deletion, segregation studies were performed when available. Clinical and radiological features were evaluated in all cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three complete and three intragenic deletions were detected. Patients present with moderate to severe short stature, mildly disproportionate growth and mild dysmorphic features. The majority suffer from joint involvement (osteochondritis dissecans and\/or early onset osteoarthritis) which has required early surgical intervention.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although individuals with heterozygous <jats:italic>ACAN<\/jats:italic> deletions exhibit phenotypic variability, it is noticeable that they present with a quite homogeneous and age\u2010dependent phenotype with a high proportion of severe joint problems.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.15237","type":"journal-article","created":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:36:06Z","timestamp":1743035766000},"page":"177-184","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Moderate to Severe Short Stature and Joint Involvement in Individuals With <i>ACAN<\/i> Deletions"],"prefix":"10.1111","volume":"103","author":[{"given":"Lucia","family":"Sentchordi\u2010Montan\u00e9","sequence":"first","affiliation":[{"name":"Department of Pediatrics Hospital Universitario Infanta Leonor Madrid Spain"},{"name":"Department of Public Maternal and Child Health Department, Faculty of Medicine Universidad Complutense de Madrid Madrid Spain"},{"name":"Institute of Medical and Molecular Genetics (INGEMM), IdiPAZ, UAM, Hospital Universitario la Paz Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisca","family":"D\u00edaz\u2010Gonzalez","sequence":"additional","affiliation":[{"name":"Institute of Medical and Molecular Genetics (INGEMM), IdiPAZ, UAM, Hospital Universitario la Paz Madrid Spain"},{"name":"Skeletal Dysplasia Multidisciplinary Unit (UMDE, ERN\u2010BOND), Hospital Universitario La Paz Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Modamio\u2010H\u00f8ybj\u00f8r","sequence":"additional","affiliation":[{"name":"Institute of Medical and Molecular Genetics (INGEMM), IdiPAZ, UAM, Hospital Universitario la Paz Madrid Spain"},{"name":"Skeletal Dysplasia Multidisciplinary Unit (UMDE, ERN\u2010BOND), Hospital Universitario La Paz Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juli\u00e1n","family":"Nevado","sequence":"additional","affiliation":[{"name":"Institute of Medical and Molecular Genetics (INGEMM), IdiPAZ, UAM, Hospital Universitario la Paz Madrid Spain"},{"name":"CIBERER, ISCIII Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavia","family":"Machado\u2010Fernandes","sequence":"additional","affiliation":[{"name":"Instituto Portugu\u00eas de Oncologia do Porto Porto 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Portugal"},{"name":"University Clinic of Genetics, Faculty of Medicine Universidade de Coimbra Coimbra Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarina G","family":"Kant","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Erasmus Medical Center Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"de Bruin","sequence":"additional","affiliation":[{"name":"Laboratory for Diagnostic Genome analysis (LDGA), Department of Clinical Genetics LUMC Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hermine A.","family":"van Duyvenvoorde","sequence":"additional","affiliation":[{"name":"Laboratory for Diagnostic Genome analysis (LDGA), Department of Clinical Genetics LUMC Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris","family":"Gonz\u00e1lez\u2010Cabaleiro","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hospital Alvaro Cunqueiro Vigo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lourdes","family":"Rey\u2010Cordo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Complejo Hospitalario Universitario de Vigo Vigo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Luis","family":"Chamorro\u2010Mart\u00edn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Complejo Hospitalario Universitario de Vigo Vigo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanesa","family":"Cancela\u2010Mu\u00f1iz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hospital Universitario de Donosti San Sebasti\u00e1n 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