Type 1 collagenopathy presenting with a Russell-Silver phenotype

Area of Science:

• Genetics and Molecular Biology
• Pediatrics
• Endocrinology

Background:

• Osteogenesis imperfecta (OI) is a group of inherited bone disorders characterized by low bone mass and fracture susceptibility.
• OI exhibits a wide clinical spectrum and can involve extra-skeletal features like blue sclera and dentinogenesis imperfecta.
• Mutations in COL1A1 and COL1A2 genes, encoding type I collagen, cause most OI cases (approx. 90%) with autosomal dominant inheritance.

Observation:

• Russell-Silver syndrome (RSS) is a heterogeneous condition presenting with short stature and a triangular facial shape, often linked to imprinting defects at 11p15.
• This report details two cases exhibiting phenotypic overlap between OI and RSS.
• Both reported cases were found to have COL1A1 mutations.

Findings:

• The study identified COL1A1 mutations in two patients with overlapping OI and RSS phenotypes.
• These findings suggest a connection between type 1 collagen defects and syndromic short stature presentations previously attributed to RSS.
• The genetic basis for some RSS cases remains unknown, indicating potential for other underlying genetic factors.

Implications:

• Type 1 collagenopathies should be considered in the differential diagnosis of syndromic short stature, particularly when OI features are present.
• This expands the diagnostic considerations for short stature beyond typical RSS or other known genetic syndromes.
• Further research is warranted to explore the genetic overlap between collagen disorders and imprinting-related syndromes.