{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T21:08:17Z","timestamp":1770066497320,"version":"3.49.0"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T00:00:00Z","timestamp":1769817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Loma Linda University School of Medicine","award":["PPM#101276"],"award-info":[{"award-number":["PPM#101276"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Langer\u2013Giedion syndrome (LGS), also known as trichorhinophalangeal syndrome type II (TRPS II; OMIM #150230), is a contiguous-gene deletion disorder caused by haploinsufficiency of TRPS1 and EXT1. Cornelia de Lange syndrome (CdLS) is genetically heterogeneous; heterozygous variants in RAD21 cause the milder CdLS type 4 phenotype (OMIM #614701). Because RAD21 lies between TRPS1 and EXT1, overlapping phenotypes may arise when all three genes are deleted. We report a unique case of a 4-year-old female presenting with a blended phenotype of Langer\u2013Giedion Syndrome (LGS) and Cornelia de Lange Syndrome (CdLS) type 4. This case is distinct from previously reported 8q deletions in three key aspects: (1) Complex Genomic Architecture: Chromosomal microarray revealed a novel complex rearrangement consisting of a 13.01 Mb mosaic interstitial deletion at 8q23.1\u2013q24.12, flanked by two large duplications (21.5 Mb at 8q11.23\u2013q23.1 and 25.78 Mb at 8q24.12\u2013q24.3). (2) Rare Mosaicism: This represents only the second reported case of mosaicism affecting this contiguous gene region. Notably, the patient demonstrates a \u201cmosaic rescue\u201d effect, where the mosaicism appears to have mitigated the neurodevelopmental phenotype (the patient is bilingual and ambulatory) while failing to protect the skeleton. (3) First Bone-Specific Therapy: The patient suffered from severe, recurrent fractures due to a synergistic \u201cdouble hit\u201d of TRPS1-related osteopenia and EXT1-related exostoses. We report the first successful use of bisphosphonate therapy (pamidronate) in this specific mosaic profile, which resulted in a complete cessation of fractures during a 12-month follow-up. This case underscores the utility of detailed microarray analysis in complex phenotypes and suggests bisphosphonates as a viable rescue therapy for refractory syndromic osteoporosis.<\/jats:p>","DOI":"10.3390\/genes17020175","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T09:48:08Z","timestamp":1770025688000},"page":"175","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Complex Case of Langer\u2013Giedion Syndrome, Cornelia de Lange Syndrome Type 4, and Hereditary Multiple Osteochondromas with Mosaic 8q23.1\u2013q24.12 Deletion"],"prefix":"10.3390","volume":"17","author":[{"given":"Samuel David Amio","family":"Valientes","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Stanford Health Care, Stanford, CA 94304, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,31]]},"reference":[{"key":"ref_1","first-page":"1197","article-title":"Molecular Definition of the Shortest Region of Deletion Overlap in the Langer-Giedion Syndrome","volume":"49","author":"Johnson","year":"1991","journal-title":"Am. 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