{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T21:22:49Z","timestamp":1787692969381,"version":"build-2784847793"},"reference-count":83,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background: Short stature is a frequent clinical problem with a broad differential diagnosis. Emerging evidence indicates that pathogenic variants in the ACAN gene represent an underrecognized cause of growth failure and are often misclassified as idiopathic short stature. Case presentation: We report two pediatric patients harboring pathogenic ACAN gene variants, both presenting with short stature and distinctive facial dysmorphism. The first patient, a 15-year-old boy, exhibited short stature, advanced bone age, and a characteristic facial gestalt, including ptosis, hypertelorism, down-slanting palpebral fissures, and fleshy auricles, features not previously described in association with aggrecanopathy. Genetic analysis revealed a novel heterozygous frameshift variant, c.5677_5684del (p.Glu1893TrpfsTer8), in exon 12 of the ACAN gene. The second patient, a 5.5-year-old girl, presented with short stature, mild facial dysmorphism (down-slanting palpebral fissures and retracted mandible), and feeding difficulties. Copy number variation analysis identified a heterozygous deletion encompassing exons 15\u201319 of the ACAN gene. In both patients, the endocrine evaluation was unremarkable, and no chronic systemic disease was identified. The genetic findings were concordant with the clinical phenotype, confirming aggrecanopathy as the underlying cause of growth failure. Conclusions: These cases further delineate the phenotypic spectrum of ACAN-related short stature and underscore the diagnostic value of genetic testing in children with unexplained or idiopathic growth failure. Importantly, we expand the dysmorphological phenotype of aggrecanopathy by describing previously unreported facial features, which may facilitate earlier clinical recognition and diagnosis. The timely identification of pathogenic variants in the ACAN gene may have significant implications for patient management and long-term outcomes.<\/jats:p>","DOI":"10.3390\/diseases14040127","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T14:59:01Z","timestamp":1775055541000},"page":"127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Aggrecanopathy as an Underrecognized Cause of Idiopathic Short Stature: The Importance of Early Genetic Confirmation for Timely Diagnosis and Management\u2014Case Reports and Literature Review"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0440-5431","authenticated-orcid":false,"given":"Aleksandra","family":"Sosin","sequence":"first","affiliation":[{"name":"Students\u2019 Scientific Group of Pediatric Auxology, Faculty of Medicine, University Children\u2019s Hospital, Jagiellonian University Medical College, 31-008 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3915-4688","authenticated-orcid":false,"given":"Tetiana","family":"Tkachuk","sequence":"additional","affiliation":[{"name":"Students\u2019 Scientific Group of Pediatric Auxology, Faculty of Medicine, University Children\u2019s Hospital, Jagiellonian University Medical College, 31-008 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Furtak","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adolescent Endocrinology, University Children\u2019s Hospital, 30-663 Krakow, Poland"},{"name":"Department of Pediatric and Adolescent Endocrinology, Chair of Pediatrics, Institute of Pediatrics, Jagiellonian University Medical College, 31-008 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Janeczko","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, Jagiellonian University Medical College, 31-008 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karol","family":"Sto\u017cek","sequence":"additional","affiliation":[{"name":"Laboratory of Cytogenetics and Molecular Genetics, University Children\u2019s Hospital, 30-663 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teofila","family":"Ksi\u0105\u017cek","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, Jagiellonian University Medical College, 31-008 Krakow, Poland"},{"name":"Laboratory of Cytogenetics and Molecular Genetics, University Children\u2019s Hospital, 30-663 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Po\u0142awska","sequence":"additional","affiliation":[{"name":"MedGen Medical Center, 02-954 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damian","family":"Loska","sequence":"additional","affiliation":[{"name":"MedGen Medical Center, 02-954 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Wardak","sequence":"additional","affiliation":[{"name":"MedGen Medical Center, 02-954 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"Starzyk","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adolescent Endocrinology, University Children\u2019s Hospital, 30-663 Krakow, Poland"},{"name":"Department of Pediatric and Adolescent Endocrinology, Chair of Pediatrics, Institute of Pediatrics, Jagiellonian University Medical College, 31-008 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3870-368X","authenticated-orcid":false,"given":"Dominika","family":"Janu\u015b","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adolescent Endocrinology, University Children\u2019s Hospital, 30-663 Krakow, Poland"},{"name":"Department of Pediatric and Adolescent Endocrinology, Chair of Pediatrics, Institute of Pediatrics, Jagiellonian University Medical College, 31-008 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12225","DOI":"10.1038\/s41598-017-12465-6","article-title":"Genetic screening confirms heterozygous mutations in ACAN as a major cause of idiopathic short stature","volume":"7","author":"Hauer","year":"2017","journal-title":"Sci. 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