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Many cases of female monozygotic (MZ) twins discordant for BWS have been reported, but no definitive conclusions have been drawn regarding the link between epigenetic defects, twinning process, and gender. Here, we report a comprehensive characterization and follow\u2010up of female MZ twins discordant for BWS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Methylation pattern at 11p15.5 and multilocus methylation disturbance (MLID) profiling were performed by pyrosequencing and MassARRAY in placental\/umbilical cord samples and postnatal tissues. Whole\u2010exome sequencing was carried out to identify MLID causative mutations. X\u2010chromosome inactivation (XCI) was determined by HUMARA test.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both twins share KCNQ1OT1:TSS\u2010DMR loss of methylation (LOM) and MLID in blood and the epigenetic defect remained stable in the healthy twin over time. KCNQ1OT1:TSS\u2010DMRLOM was nonhomogeneously distributed in placental samples and the twins showed the same severely skewed XCI pattern. No MLID\u2010causative mutations were identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the first report on BWS\u2010discordant twins with methylation analyses extended to extraembryonic tissues. The results suggest that caution is required when attempting prenatal diagnosis in similar cases. Although the causative mechanism underlying LOM remains undiscovered, the XCI pattern and mosaic LOM suggest that both twinning and LOM\/MLID occurred after XCI commitment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1386","type":"journal-article","created":{"date-parts":[[2020,7,6]],"date-time":"2020-07-06T09:37:38Z","timestamp":1594028258000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["(Epi)genetic profiling of extraembryonic and postnatal tissues from female monozygotic twins discordant for Beckwith\u2013Wiedemann syndrome"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9517-6997","authenticated-orcid":false,"given":"Laura","family":"Fontana","sequence":"first","affiliation":[{"name":"Medical Genetics Department of Pathophysiology &amp; Transplantation Universit\u00e0 degli Studi di Milano Milano Italy"},{"name":"Research Laboratories Coordination Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria F.","family":"Bedeschi","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia A.","family":"Cagnoli","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jole","family":"Costanza","sequence":"additional","affiliation":[{"name":"Research Laboratories Coordination Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Persico","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Unit Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano Italy"},{"name":"Department of ClinicalSciences and Community Health Universit\u00e0 degli Studi di Milano Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvana","family":"Gangi","sequence":"additional","affiliation":[{"name":"NICU Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Porro","sequence":"additional","affiliation":[{"name":"Pediatric Physical Medicine &amp; 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