Clinical and Molecular Diagnosis of Beckwith-Wiedemann Syndrome with Single- or Multi-Locus Imprinting Disturbance

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Apr 3

PMID 33810554

Citations 18

Authors

Laura Fontana

Silvia Tabano

Silvia Maitz

Patrizia Colapietro

Emanuele Garzia

Alberto Giovanni Gerli

Silvia Maria Sirchia

Monica Miozzo

Affiliations

Soon will be listed here.

Abstract

Beckwith-Wiedemann syndrome (BWS) is a clinically and genetically heterogeneous overgrowth disease. BWS is caused by (epi)genetic defects at the 11p15 chromosomal region, which harbors two clusters of imprinted genes, / and /, regulated by differential methylation of imprinting control regions, :IG DMR and :TSS DMR, respectively. A subset of BWS patients show multi-locus imprinting disturbances (MLID), with methylation defects extended to other imprinted genes in addition to the disease-specific locus. Specific (epi)genotype-phenotype correlations have been defined in order to help clinicians in the classification of patients and referring them to a timely diagnosis and a tailored follow-up. However, specific phenotypic correlations have not been identified among MLID patients, thus causing a debate on the usefulness of multi-locus testing in clinical diagnosis. Finally, the high incidence of BWS monozygotic twins with discordant phenotypes, the high frequency of BWS among babies conceived by assisted reproductive technologies, and the female prevalence among BWS-MLID cases provide new insights into the timing of imprint establishment during embryo development. In this review, we provide an overview on the clinical and molecular diagnosis of single- and multi-locus BWS in pre- and post-natal settings, and a comprehensive analysis of the literature in order to define possible (epi)genotype-phenotype correlations in MLID patients.

Citing Articles

Multi-locus imprinting disturbance (MLID): interim joint statement for clinical and molecular diagnosis.

Mackay D, Gazdagh G, Monk D, Brioude F, Giabicani E, Krzyzewska I Clin Epigenetics. 2024; 16(1):99.

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Unusual Presentation of Beckwith-Wiedemann Syndrome in an Extremely Low Birth Weight Infant.

Alhamdan A, Shajira E Cureus. 2024; 16(6):e63099.

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Joint effects of CD8A and ICOS in Long QT Syndrome (LQTS) and Beckwith-Wiedemann Syndrome (BWS).

Meng L, Li Y, Lv T, Lv C, Liu L, Zhang P J Cardiothorac Surg. 2024; 19(1):321.

PMID: 38845009 PMC: 11155187. DOI: 10.1186/s13019-024-02804-w.

Epigenetics and environmental health.

Zhang M, Hu T, Ma T, Huang W, Wang Y Front Med. 2024; 18(4):571-596.

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The impact of inversions across 33,924 families with rare disease from a national genome sequencing project.

Pagnamenta A, Yu J, Walker S, Noble A, Lord J, Dutta P Am J Hum Genet. 2024; 111(6):1140-1164.

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