Maternal Cell-Free DNA Analysis in a Fetus Affected by Beckwith-Wiedemann Syndrome: Potential for Prenatal Diagnosis

Beckwith-Wiedemann syndrome (BWS) is a condition present from birth that involves excessive growth and is linked to changes in specific genes located on chromosome 11p15.5. Prenatal diagnosis is mainly based on imaging findings such as macrosomia, macroglossia, and omphalocele, but detection remains difficult. We report a case of a fetus suspected of having BWS based on prenatal ultrasound and MRI. A female infant was delivered via cesarean section at 37 weeks and one day of gestation, showing macrosomia, macroglossia, and other clinical features consistent with BWS. To explore potential biomarkers for prenatal diagnosis of BWS, maternal blood was collected at 36 and 37 weeks of gestation and postpartum days 1 and 5. Cell-free DNA (cfDNA) analysis revealed a bimodal fragment size distribution with peaks at 144 and 166 bp during pregnancy. After delivery, the 144 bp peak disappeared, resulting in a unimodal pattern. The fetal fraction was elevated during pregnancy (33.9-34.5%) and decreased rapidly postpartum (to 3.4%). These findings suggest an increased release of fetal-derived cfDNA with BWS-affected fetuses. This case highlights the potential utility of cfDNA analysis as a noninvasive biomarker for BWS.