Ultrasound and molecular prenatal diagnosis of Beckwith-Wiedemann syndrome: Two case reports

Beckwith-Wiedemann syndrome (BWS) is a rare genetic disease, characterized by macrosomia, congenital malformations and tumor predisposition, associated with genetic and epigenetic alterations in the 11p15 region. Most cases are diagnosed after birth, with prenatal diagnosis being difficult and depending on the identification of specific ultrasound anomalies, namely macrosomia, macroglossia, omphalocele and renal dysplasia. Case 1: Ultrasound diagnosis at 13 weeks of isolated omphalocele with normal array. At 20 weeks, there were shortened fetal long bones, foot deformity, macroglossia, corpus callosum hypoplasia and bilateral nephromegaly. Due to the polymalformative syndrome, a termination of pregnancy (TOP) was performed. The anatomopathological study of the placenta identified mesenchymal dysplasia. The search for the methylation pattern of the 11p15 region by MS-MLPA was normal and the molecular study of the CDKN1C gene identified a likely pathogenic variant, inherited from the mother. Case 2: Morphological ultrasound at 21 weeks revealed macrosomia, macroglossia, omphalocele, bilateral renal dysplasia, and hydramnios. The cytogenetic study, after amniocentesis, was normal (46,XX karyotype). TOP was performed. The anatomopathological study of the fetus confirmed the described malformations and the one concerning the placenta identified placentomegaly. The search for the methylation pattern of the 11p15 region by MS-MLPA revealed abnormal methylation. These results confirmed the diagnosis of BWS in both cases. Prenatal ultrasound suspicion of this pathology is extremely important to guide the conduct in pregnancy and/or the prevention of perinatal complications. Shortened fetal long bones and foot deformity complement the broad spectrum of this syndrome. Positive molecular tests allow confirming the diagnosis, assessing the risk of recurrence and guiding the surveillance of future pregnancy.