Utility of Prenatal Screening and Diagnostic Testing for Skeletal Dysplasias

With over 450 described skeletal dysplasia syndromes, prenatal ultrasound findings suggestive of skeletal dysplasia often have a wide differential diagnosis, and most accurate diagnoses are often made through molecular genetic testing. Previous studies have analyzed diagnostic yield of certain prenatal genetic testing methodologies, but there are limited data comparing relative detection rates in cases of suspected skeletal dysplasia. Our study aimed to compare diagnostic yields of available prenatal genetic testing options in suspected skeletal dysplasia cases.

We conducted a multicenter retrospective chart review of 118 cases with ultrasound findings suggestive of skeletal dysplasia over 10 years. Fetal biometry and genetic testing were analyzed for diagnostic accuracy. Theoretical diagnostic yields for various testing methods were also evaluated.

Among the 99 individuals who underwent genetic testing, 52 received a molecular diagnosis. Skeletal dysplasia panels and exome sequencing could detect 96% of the syndromes, while single-gene noninvasive prenatal testing could detect 51.9%. In 7.69% of molecularly confirmed cases, ultrasonographic suspicion was incorrect compared to molecular diagnoses.

Our findings highlight the crucial role of diagnostic molecular testing in accurately diagnosing suspected skeletal dysplasia, determining recurrence risk, and providing family guidance.