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

## TL;DR

A case report describes a rare syndrome involving COL1A1 mutations with features of osteogenesis imperfecta and Ehlers–Danlos syndrome in a patient with childhood-onset hypopituitarism.

## Contribution

The report expands the known phenotypic spectrum of COL1A1 mutations and supports the existence of a COL1-related overlap syndrome.

## Key findings

- A novel COL1A1 exon 14 variant (c.940G > A, p.Gly314Arg) was identified in a patient with multiple clinical features of a COL1-related overlap syndrome.
- The patient exhibited disproportionate short stature, grayish-blue sclerae, fractures, joint hypermobility, and hypopituitarism.
- Imaging revealed bowing of forearm bones and multiple Wormian bones, supporting the diagnosis of a COL1-related overlap disorder.

## Abstract

Background: Type I collagen is the most abundant protein of the extracellular matrix. Pathogenic variants in COL1A1 or COL1A2 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. Methods: 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. Results: Genetic testing confirmed a novel heterozygous COL1A1 exon 14 variant (c.940G > A, p.Gly314Arg), presenting with a phenotype consistent with a COL1-related overlap syndrome. Conclusions: This case expands the phenotypic spectrum of COL1A1 mutations and supports the concept of COL1-related phenotypic overlap.