Beckwith–Wiedemann Syndrome Diagnosed in the Early Second Trimester in Two Fetuses with Isolated Omphalocele

Abstract

Beckwith–Wiedemann syndrome (BWS) is an imprinting disorder caused by various genetic or epigenetic alterations involving growth regulatory genes located on chromosome 11p15.5 region. Conventionally, most cases of BWS are diagnosed during the neonatal period or early childhood. Early prenatal diagnosis is very important because it provides information regarding the prognosis, guidance of delivery preparation, and postnatal care plan. We report two cases of BWS diagnosed in utero using exome sequencing (ES) after the early identification of fetal omphalocele and normal findings of microarray and methylation analyses. Case 1 carried a de novo CDKN1C c.694C>T (p.Gln232*) variant. Case 2 carried a familial CDKN1C c.827_828delinsAA (p.Phe276*) variant; another member in the family presented with features of BWS. In both cases, no macrosomia and visceromegaly were demonstrated. Although fetal omphalocele was identified in the first trimester, invasive testing was delayed to the early second trimester for methylation in the two cases. Fetal omphalocele should not be regarded as just an abdominal wall defect. When a fetal omphalocele was identified, a detailed family history, especially with searching for the signs of BWS in familial members, should be undertaken. For an omphalocele, ES is an option for patients after normal microarray and methylation analyses.