A Complex Case of Langer-Giedion Syndrome, Cornelia de Lange Syndrome Type 4, and Hereditary Multiple Osteochondromas with Mosaic 8q23.1-q24.12 Deletion.
AI interpretation is pending for this paper.
Open original publication →What the AI sees
Not AI summarized yet.
Research significance
Pending deeper interpretation.
Source abstract
Langer-Giedion 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-Giedion 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-q24.12, flanked by two large duplications (21.5 Mb at 8q11.23-q23.1 and 25.78 Mb at 8q24.12-q24.3). (2) Rare Mosaicism: This represents only the second reported case of mosaicism affecting this contiguous gene region. Notably, the patient demonstrates a "mosaic rescue" 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 "double hit" 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.