RESUMO
BACKGROUND: Disorders involving the musculoskeletal system are often identified with short stature and a range of orthopedic problems. The clinical and genetic heterogeneity of these diseases along with several characteristic overlaps makes definitive diagnosis difficult for clinicians. Hence, using molecular testing in addition to conventional tests becomes essential for appropriate diagnosis and management. METHODS: Comprehensive clinical examination, detailed pretest and posttest counseling, molecular diagnosis with next-generation sequencing (NGS), genotype-phenotype correlation and Sanger sequencing for targeted variant analysis. RESULTS: This manuscript reports a molecular spectrum of variants in 34 orthopedic cases referred to a single genetic unit attached to a tertiary care hospital. The diagnostic yield of NGS-based tests coupled with genetic counseling and segregation analysis was 79% which included 7 novel variants. In about 53% (i.e. 18/34 cases), molecular testing outcome was actionable since 8 of the 18 underwent prenatal diagnosis, as they were either in their early gestation or had planned a pregnancy subsequent to molecular testing, while ten cases were premaritally/prenatally counseled for the families to take informed decisions as they were in the reproductive age. CONCLUSIONS: The report highlights the importance of NGS-based tests even in a low resource setting as it helps patients, families and healthcare providers in reducing the economic, social and emotional burden of these disorders.
