Prenatal presentation in two fetuses with features of Beckwith Wiedemann syndrome—An unexpected diagnosis of androgenetic chimera and its clinical implications

• Published in: American journal of medical genetics. Part A Vol. 188; no. 5; pp. 1562 - 1567
• Main Authors: Yu, Pui‐Tak, Shu, Wendy, Mok, Sau‐Lan, Hui, Pui‐Wah, Chan, Lin‐Wai, Kwok, Ka‐Yin, Chan, Kelvin Y. K., Lo, Tsz‐Kin, Chung, Brian H. Y., Luk, Ho‐Ming, Kan, Anita S. Y.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01-05-2022; Wiley Subscription Services, Inc
• Subjects: androgenetic biparental chimera; Androgens; Beckwith Wiedemann syndrome (BWS); Beckwith-Wiedemann Syndrome - diagnosis; Beckwith-Wiedemann Syndrome - genetics; Chimera; Chromosome 11; DNA Methylation - genetics; Dysplasia; Edema; Female; Fetus; Fetuses; genome wide paternal uniparental disomy (GWpUPD); Genomes; Genomic Imprinting - genetics; Genotyping; Humans; Lethality; Mesenchyme; Phenotypes; Placenta; Pregnancy; Tumors; Uniparental disomy; Uniparental Disomy - genetics; Beckwith Wiedemann syndrome (BWS); chimera; genome wide paternal uniparental disomy (GWpUPD); androgenetic biparental chimera
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.62665

Beckwith Wiedemann Syndrome (BWS, OMIM 130650) is an imprinting disorder that may present antenatally with a constellation of sonographic features namely polyhydramnios, macrosomia, macroglossia, omphalocele, placental mesenchymal dysplasia, cardiomegaly, nephromegaly, fetal hydrops, and other rare anomalies. Paternal uniparental disomy in chromosome 11p15 imprinting region accounts for 20% of all BWS, and 8% among those were due to genome‐wide paternal uniparental disomy (GWpUPD). GWpUPD is a rare condition and usually results in prenatal lethality. The 31 liveborns reported in the literature demonstrate female predominance in surviving GWpUPD. Here, we reported two prenatal cases which initially presented with features suggestive of BWS, which subsequently were confirmed to have GWpUPD. Further trio SNP genotyping analysis using SNP‐based chromosomal microarray revealed androgenetic biparental chimera as the underlying cause. Finally, we highlighted the importance of recognizing GWpUPD as a possible cause in a fetus presenting with BWS phenotype, as it carried a different disease prognosis, tumor predisposition, manifestations of other imprinting disorders, and possibility in unmasking autosomal recessive disorders from the paternal alleles.