A single-centre study of genetic mutations, audiology, echocardiogram and pulmonary function in Saudi children with...

Area of Science:

• Genetics
• Pediatrics
• Connective Tissue Disorders

Background:

• Osteogenesis imperfecta (OI) is a group of inherited disorders characterized by bone fragility.
• Patients with OI often present with extra-skeletal manifestations including hearing loss, cardiac abnormalities, and pulmonary dysfunction.
• Understanding these extra-skeletal features is crucial for comprehensive patient management.

Purpose of the Study:

• To investigate the genetic mutations in children with OI.
• To determine the prevalence of hearing issues, cardiac complications, and impaired pulmonary function in pediatric OI patients.
• To describe the spectrum of extra-skeletal features in a cohort of Saudi children with OI.

Main Methods:

• A cross-sectional study involving 23 Saudi children diagnosed with OI (aged 6 months to 18 years).
• OI types were classified using the revised Sillence classification.
• Genetic analysis was performed using whole exome sequencing.
• Hearing was assessed via audiometry and/or otoacoustic emissions.
• Cardiac defects were screened using echocardiograms.
• Pulmonary function was evaluated through spirometry.

Main Results:

• The study identified OI types I, III, and IV, with a majority having type III (16 patients).
• Genetic sequencing revealed autosomal dominant mutations in 66.6% and autosomal recessive mutations in 33.3% of cases.
• Screening indicated a high prevalence of hearing loss (53%), congenital cardiac malformations (26%), and restrictive lung disease (70%).

Conclusions:

• Significant extra-skeletal features are prevalent in children with OI.
• A high yield of genetic mutations was associated with OI in this cohort.
• Further research is recommended to establish screening protocols for extra-skeletal manifestations in pediatric OI patients.