Genetic causes of the skeletal system abnormalities diagnosed by prenatal sonography with the use of exome sequencing: single institution experience.

Objectives Skeletal system abnormalities are a heterogenous group of disorders caused by teratogens, environmental factors, chromosomal abnormalities or monogenic disorders. Monogenic causes of the skeletal disorders in postnatal patients are periodically revised by the International Skeletal Dysplasia Society (ISDS) and published as Nosology and Classification of Genetic Skeletal Disorders. The aim of this study was to analyze genetic causes of the skeletal system abnormalities diagnosed by prenatal sonography and to establish diagnostic protocol with regard to extended genetic testing in this group of patients. Methods The study included all consecutive patients with sonographic abnormalities of the skeletal system in singleton pregnancies evaluated in a single ultrasound department during one year. Results The study group consisted of 55 fetuses. Chromosomal abnormalities were detected in 24 fetuses. Single gene pathogenic or likely pathogenic variants in 14 different genes were detected in 18 fetuses. Seven genes have already been listed in the ISDS Nosology. The remaining seven genes were out of this list. Conclusions In fetuses with localized abnormality of the skeletal system accompanied by additional structural anomalies chromosomal abnormality is the most common diagnosis. Exome sequencing increases the diagnostic yield in fetuses with skeletal system abnormalities especially in case of multiple abnormalities. This article is protected by copyright. All rights reserved.