Placental Mesenchymal Dysplasia and Beckwith–Wiedemann Syndrome
1
Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga 849-8501, Japan
2
Department of Obstetrics and Gynecology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan
*
Author to whom correspondence should be addressed.
Cancers 2022, 14(22), 5563; https://doi.org/10.3390/cancers14225563
Submission received: 18 October 2022
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Accepted: 10 November 2022
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Published: 12 November 2022
(This article belongs to the Special Issue Beckwith–Wiedemann Spectrum and Cancer)
Simple Summary
Placental mesenchymal dysplasia (PMD) is a morphological abnormality resembling partial hydatidiform moles without abnormal trophoblastic proliferation. In PMD, approximately 20% of fetuses have Beckwith–Wiedemann syndrome (BWS), and approximately 20% of BWS fetuses are associated with PMD. In addition, PMD is a cardinal feature of BWS, and paternal uniparental diploidy/biparental diploidy mosaicism (also called androgenetic/biparental mosaicism) has been found in both BWS and PMD. This suggests that there is a molecular link between BWS and PMD. In this review, we focus on the etiologies of BWS and PMD and describe the molecular link between them. Both conditions are imprinting disorders that, depending on the case, may share or differ in molecular characteristics. These observations raise questions concerning the timing of the occurrence of the molecularly abnormal cells during the postfertilization period and the effects of these abnormalities on cell fates after implantation.
Abstract
Placental mesenchymal dysplasia (PMD) is characterized by placentomegaly, aneurysmally dilated chorionic plate vessels, thrombosis of the dilated vessels, and large grapelike vesicles, and is often mistaken for partial or complete hydatidiform mole with a coexisting normal fetus. Androgenetic/biparental mosaicism (ABM) has been found in many PMD cases. Beckwith–Wiedemann syndrome (BWS) is an imprinting disorder with complex and diverse phenotypes and an increased risk of developing embryonal tumors. There are five major causative alterations: loss of methylation of imprinting control region 2 (KCNQ1OT1:TSS-DMR) (ICR2-LOM), gain of methylation at ICR1 (H19/IGF2:IG-DMR) (ICR1-GOM), paternal uniparental disomy of 11 (pUPD11), loss-of-function variants of the CDKN1C gene, and paternal duplication of 11p15. Additional minor alterations include genetic variants within ICR1, paternal uniparental diploidy/biparental diploidy mosaicism (PUDM, also called ABM), and genetic variants of KCNQ1. ABM (PUDM) is found in both conditions, and approximately 20% of fetuses from PMD cases are BWS and vice versa, suggesting a molecular link. PMD and BWS share some molecular characteristics in some cases, but not in others. These findings raise questions concerning the timing of the occurrence of the molecularly abnormal cells during the postfertilization period and the effects of these abnormalities on cell fates after implantation.
