Intersecting Pathologies: COL1A1-Related Syndrome in the Setting of Childhood-Onset Hypopituitarism: Case Report and Literature Review

<b>Background</b>: Type I collagen is the most abundant protein of the extracellular matrix. Pathogenic variants in <i>COL1A1</i> or <i>COL1A2</i> are classically associated with osteogenesis imperfecta (OI) and Ehlers-Danlos syndrome (EDS). An emerging clinical entity-COL1-related overlap disorder-encompasses individuals exhibiting phenotypic features of both conditions. <b>Methods</b>: We report a 55-year-old male presenting with disproportionate short stature, grayish-blue sclerae, multiple fractures, long bone deformities, joint hypermobility, and atrophic surgical scarring. The patient also had long-standing, untreated childhood-onset hypopituitarism. Imaging studies revealed numerous prior fractures, bowing of forearm bones, and multiple Wormian bones. <b>Results</b>: Genetic testing confirmed a novel heterozygous <i>COL1A1</i> exon 14 variant (c.940G > A, p.Gly314Arg), presenting with a phenotype consistent with a COL1-related overlap syndrome. <b>Conclusions</b>: This case expands the phenotypic spectrum of <i>COL1A1</i> mutations and supports the concept of COL1-related phenotypic overlap.