title: Clinical and molecular analyses of Beckwith-Wiedemann syndrome: Comparison between spontaneous conception and assisted reproduction techniques.
abstract: Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome characterized by an excessive prenatal and postnatal growth, macrosomia, macroglossia, and hemihyperplasia. The molecular basis of this syndrome is complex and heterogeneous, involving genes located at 11p15.5. BWS is correlated with assisted reproductive techniques. BWS in individuals born following assisted reproductive techniques has been found to occur four to nine times higher compared to children with to BWS born after spontaneous conception. Here, we report a series of 187 patients with to BWS born either after assisted reproductive techniques or conceived naturally. Eighty-eight percent of BWS patients born via assisted reproductive techniques had hypomethylation of KCNQ1OT1:TSS-DMR in comparison with 49% for patients with BWS conceived naturally. None of the patients with BWS born via assisted reproductive techniques had hypermethylation of H19/IGF2:IG-DMR, neither CDKN1 C mutations nor patUPD11. We did not find differences in the frequency of multi-locus imprinting disturbances between groups. Patients with BWS born via assisted reproductive techniques had an increased frequency of advanced bone age, congenital heart disease, and decreased frequency of earlobe anomalies but these differences may be explained by the different molecular background compared to those with BWS and spontaneous fertilization. We conclude there is a correlation of the molecular etiology of BWS with the type of conception. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz-UAM, Madrid, Spain.|CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.
authors.forename: Jair
authors.initials: J
authors.lastname: Tenorio
authors.affiliation: Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz-UAM, Madrid, Spain.|CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.
authors.forename: Valeria
authors.initials: V
authors.lastname: Romanelli
authors.affiliation: Imprinting and Cancer Group, Cancer Epigenetic and Biology Program (PEBC), Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Barcelona, Spain.
authors.forename: Alex
authors.initials: A
authors.lastname: Martin-Trujillo
authors.affiliation: Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz-UAM, Madrid, Spain.|CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.
authors.forename: García-Moya
authors.initials: GM
authors.lastname: Fernández
authors.affiliation: Centro Nacional de Genética Médica, ANLIS Dr. Carlos G. Malbrán, Buenos Aires, Argentina.
authors.forename: Mabel
authors.initials: M
authors.lastname: Segovia
authors.affiliation: Centro Nacional de Genética Médica, ANLIS Dr. Carlos G. Malbrán, Buenos Aires, Argentina.
authors.forename: Claudia
authors.initials: C
authors.lastname: Perandones
authors.affiliation: CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.|Unitat de Genética, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Pérez Jurado
authors.affiliation: Cancer Epigenetics Group, Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
authors.affiliation: Unidad de Epigenética del Cáncer, Instituto Universitario de Oncología, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Fraga
authors.affiliation: Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz-UAM, Madrid, Spain.|CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Arias
authors.affiliation: Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz-UAM, Madrid, Spain.|CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Gordo
authors.affiliation: Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz-UAM, Madrid, Spain.|CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Dapía
authors.affiliation: Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz-UAM, Madrid, Spain.|CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Mena
authors.affiliation: Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz-UAM, Madrid, Spain.|CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Palomares
authors.affiliation: Molecular Genetics Laboratory, Research Unit, Hospital Universitario Araba, Vitoria-Gasteiz, Spain.
authors.forename: Guiomar
authors.initials: G
authors.lastname: Pérez de Nanclares
authors.affiliation: Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz-UAM, Madrid, Spain.|CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Nevado
authors.affiliation: Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz-UAM, Madrid, Spain.|CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.
authors.forename: Sixto
authors.initials: S
authors.lastname: García-Miñaur
authors.affiliation: Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz-UAM, Madrid, Spain.|CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Santos-Simarro
authors.affiliation: Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz-UAM, Madrid, Spain.|CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Martinez-Glez
authors.affiliation: Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz-UAM, Madrid, Spain.|CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Vallespín
authors.affiliation: Imprinting and Cancer Group, Cancer Epigenetic and Biology Program (PEBC), Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Monk
authors.affiliation: Instituto de Genética Médica y Molecular (INGEMM)-IdiPAZ, Hospital Universitario La Paz-UAM, Madrid, Spain. pablo.lapunzina@salud.madrid.org.|CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Madrid, Spain. pablo.lapunzina@salud.madrid.org.
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapunzina
mesh_terms: D001506:Beckwith-Wiedemann Syndrome / Q000175:diagnosis* / Q000235:genetics*; D002503:Centromere; D002880:Chromosomes, Human, Pair 11; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D005306:Fertilization; D056726:Genetic Association Studies; D018392:Genomic Imprinting; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010641:Phenotype; D012042:Registries; D027724:Reproductive Techniques, Assisted; D013030:Spain; D016615:Telomere
keywords: Beckwith-Wiedemann syndrome; H19/IGF2:IG-DMR; KCNQ1OT1:TSS-DMR; assisted reproductive techniques; genome-wide hypomethylation; imprinting disorders; multi-locus imprinting disturbance