Genotype-Phenotype Correlation Insights in a Rare Case Presenting with Multiple Osteodysplastic Syndromes

Area of Science:

• Genetics and Molecular Biology
• Skeletal Dysplasias
• Medical Case Reports

Background:

• Osteodysplastic syndromes are diverse genetic disorders affecting bone and connective tissue development.
• Characterized by heterogeneous clinical and genetic presentations impacting bone density and structure.
• This report details a complex case in a 48-year-old female with bone dysplasia, hyperostosis, and partial tooth agenesis.

Observation:

• A 48-year-old female presented with a complex medical history involving bone dysplasia, hyperostosis, and partial tooth agenesis.
• Whole Exome Sequencing (WES) and Sanger sequencing were employed for comprehensive genetic analysis.
• Molecular modeling and dynamics simulations were utilized to investigate the functional impact of identified genetic variants.

Findings:

• Multiple pathogenic variants were identified in genes including CREB3L1, SLCO2A1, SFRP4, LRP5, and LRP6.
• The patient exhibited homozygosity for rare alleles linked to osteogenesis imperfecta type XVI, primary hypertrophic osteoarthropathy, and metaphyseal dysplasia Pyle type.
• Additional variants associated with autosomal dominant endosteal hyperostosis and increased fracture risk were detected, with two predicted to cause abnormal splicing.

Implications:

• This case underscores the diagnostic challenges posed by the rare coexistence of multiple osteodysplastic syndromes in a single individual.
• Highlights the critical need for early genetic investigation and counseling in complex cases with overlapping phenotypic traits.
• Facilitates timely clinical interventions, prevention, and management of manifestations associated with these rare bone disorders.