Prenatal Genetic Testing for Beckwith-Wiedemann Syndrome: Considerations, Challenges and Observations (A Real-World Study).

objectivePrenatal genetic testing for imprinting disorders is rarely requested with the exception of Beckwith-Wiedemann syndrome (BWS) which is associated with specific ultrasound findings (e.g., placental mesenchymal dysplasia, omphalocele). However, genetic testing for BWS is challenging as aberrant DNA methylation has to be addressed which often occur as mosaicism. As a growing number of requests for prenatal BWS testing is observed, data from genetic prenatal BWS testing was compiled to delineate its suitability as well as limitations.

methodThree European laboratories compiled the experiences from 646 prenatal samples. The samples were analysed by methylation-specific assays targeting the imprinting centres in 11p15.5, in a sub-cohort CDKN1C was sequenced.

resultsThe overall detection rate for BWS specific molecular disturbances was 9.75%, and the spectrum of alterations reflected that from postnatal BWS cohorts. The rate of failing samples was in total 4.3%, nearly all failures were observed in native samples.

conclusionPrenatal testing for BWS should be considered in pregnancies with ultrasound findings or family history suggestive for BWS. In the majority of tests, evaluable results can be achieved, though mosaicism can never be excluded and therefore false-negative results are possible.