{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T12:44:58Z","timestamp":1768481098575,"version":"3.49.0"},"reference-count":20,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T00:00:00Z","timestamp":1702857600000},"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 Genetics"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly (MDMHB) is an ultra\u2010rare skeletal dysplasia caused by heterozygous intragenic <jats:italic>RUNX2<\/jats:italic> duplications, comprising either exons 3 to 5 or exons 3 to 6 of <jats:italic>RUNX2<\/jats:italic>. In this study, we describe a 14\u2010year\u2010old Belgian boy with metaphyseal dysplasia with maxillary hypoplasia but without brachydactyly. Clinical and radiographic examination revealed mild facial dysmorphism, dental anomalies, enlarged clavicles, genua valga and metaphyseal flaring and thin cortices with an osteoporotic skeletal appearance. Exome sequencing led to the identification of a de novo heterozygous tandem duplication within <jats:italic>RUNX2<\/jats:italic>, encompassing exons 3 to 7. This duplication is larger than the ones previously reported in MDMHB cases since it extends into the C\u2010terminal activation domain of RUNX2. We review previously reported cases with MDMHB and highlight the resemblance of this disorder with Pyle disease, which may be explained by intersecting molecular pathways between RUNX2 and sFRP4. This study expands our knowledge on the genotypic and phenotypic characteristics of MDMHB and the role of RUNX2 in rare bone disorders.<\/jats:p>","DOI":"10.1111\/cge.14474","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T09:40:28Z","timestamp":1702892428000},"page":"434-439","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp><i>RUNX2<\/i><\/scp>\u2010related metaphyseal dysplasia with maxillary hypoplasia: A rare skeletal disorder resembling <scp><i>SFRP4<\/i><\/scp>\u2010related Pyle disease"],"prefix":"10.1111","volume":"105","author":[{"given":"Ewa","family":"Hordyjewska\u2010Kowalczyk","sequence":"first","affiliation":[{"name":"Laboratory for Skeletal Dysplasia Research, Department of Human Genetics KU Leuven  Leuven Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wim","family":"Wuyts","sequence":"additional","affiliation":[{"name":"Department 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