Pathways to enhancing prenatal diagnosis of skeletal dysplasias

Skeletal dysplasias are a group of Mendelian disorders that variably alter the development of the musculoskeletal system and phenotypically range from mild short stature syndromes to severe perinatal or neonatal morbidity. Prenatal diagnosis of these conditions can be challenging due to the lack of precision with ultrasound imaging compared to postnatal radiographs as well as the known allelic heterogeneity and phenotypic variability underlying these conditions. Historically, the sonographic approach for phenotyping these conditions lacked genotypic specificity and counseling focused on predicting perinatal lethality. However, recent advances in genomic medicine and prenatal ultrasound resolution have enabled more precise diagnosis and individualized counseling. The following review provides a comprehensive overview of best practices for prenatal ultrasonography and molecular work-up for skeletal dysplasias and provides a standardized evidence-based framework for evaluation.