Clinical and molecular diagnosis of beckwith-wiedemann syndrome with single-or multi-locus imprinting disturbance

Laura Fontana, Silvia Tabano, Silvia Maitz, Patrizia Colapietro, Emanuele Garzia, Alberto Giovanni Gerli, Silvia Maria Sirchia, Monica Miozzo

Research output: Contribution to journalReview articlepeer-review


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, IGF2/H19 and CDKN1C/KCNQ1OT1, regulated by differential methylation of imprinting control regions, H19/IGF2:IG DMR and KCNQ1OT1: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.

Original languageEnglish
Article number3445
JournalInternational Journal of Molecular Sciences
Issue number7
Publication statusPublished - Apr 1 2021


  • Beckwith-Wiedemann syndrome
  • Clinical diagnosis
  • Discordant monozygotic twins
  • Molecular testing
  • Multilocus imprinting disturbance
  • X-chromosome inactivation

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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