Fragile but flexible: A rare case report of <i>COL1</i>-related overlap disorder

Osteogenesis imperfecta (OI) and Ehlers–Danlos syndrome (EDS) are inherited connective tissue disorders with overlapping phenotypic features such as bone fragility, joint hypermobility, and skin laxity. Mutations in COL1A1 or COL1A2 may lead to a combined phenotype now referred to as COL1 -related overlap disorder (C1ROD), a rare clinical entity. We report a 3.5-year-old boy presenting with short stature, developmental delay, and recurrent fractures following trivial trauma. He exhibited blue sclerae, hypotonia, generalized joint laxity, and loose skin folds. Radiographs showed osteopenia and dual-energy X-ray absorptiometry confirmed osteoporosis. Biochemical parameters were normal. There was a similar phenotype in the father, suggesting autosomal dominant inheritance. Whole-exome sequencing identified a heterozygous splice-site mutation in COL1A2 (c.432+1G&gt;A), confirming a diagnosis of C1ROD. The child was started on intravenous zoledronic acid biannually, along with calcium and vitamin D supplementation. Our case highlights the importance of considering C1ROD in patients with overlapping features of OI and EDS, particularly with a positive family history. Genetic confirmation facilitates accurate diagnosis, anticipatory guidance, and targeted treatment such as early bisphosphonate therapy.