title: Silver-Russell syndrome due to paternal H19/IGF2 hypomethylation in a twin girl born after in vitro fertilization.
abstract: Silver-Russell syndrome (SRS) is a clinically and genetically heterogeneous syndrome characterized by severe intrauterine and postnatal growth retardation, facial dysmorphism and body asymmetry. One of the main molecular mechanisms leading to the syndrome involves methylation abnormalities of chromosome 11p15. In the last decades, an increase of imprinting disorders have been reported in children born from assisted reproductive technology (ART); however there is currently little evidence linking SRS and ART. Only few infants with SRS born using ART, supported by molecular analysis, have been described. We report on a twin-girl conceived using intracytoplasmic sperm injection (ICSI) diagnosed with SRS. Molecular studies revealed a hypomethylation of the paternal H19/IGF2 Imprinting Control Region. Her twin sister had a normal prenatal and postnatal growth and a normal methylation pattern of the chromosome 11p15. This is the second reported case of a twin infant with SRS conceived using ART with hypomethylation of H19/IGF2; it provides additional evidence of a possible relationship between ART procedures and methylation defects observed in SRS. Given the clinical heterogeneity of SRS, and the increased risk of multiple and preterm births in the ART-conceived children, it is possible that a number of cases of SRS remains undiagnosed in this population. Future studies should investigate the possible link between ART and SRS, in order to better understand the causes of epimutations in ART pregnancies, and to help clinicians to adequately counsel parents who approach to ART and to assess the opportunity of a long-term follow-up of children conceived using ART.
authors.affiliation: Department of Maternal and Paediatric Sciences, Neonatology, St. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Cocchi
authors.forename: Concetta
authors.initials: C
authors.lastname: Marsico
authors.forename: Anita
authors.initials: A
authors.lastname: Cosentino
authors.forename: Chiara
authors.initials: C
authors.lastname: Spadoni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rocca
authors.forename: Agostina
authors.initials: A
authors.lastname: De Crescenzo
authors.forename: Andrea
authors.initials: A
authors.lastname: Riccio
mesh_terms: D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11; D019175:DNA Methylation; D005260:Female; D005307:Fertilization in Vitro; D018392:Genomic Imprinting; D006801:Humans; D007231:Infant, Newborn; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D056730:Silver-Russell Syndrome / Q000175:diagnosis / Q000235:genetics*; D014427:Twins
chemical_list: C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D007335:Insulin-Like Growth Factor II
keywords: Silver-Russell syndrome; imprinting disorders; in vitro fertilization
references.citation: J Med Genet. 2008 Apr;45(4):193-9
references.pmid: 18156438
references.citation: Pediatr Dev Pathol. 2008 Jul-Aug;11(4):329-31
references.pmid: 18494536
references.citation: J Med Genet. 2006 Dec;43(12):902-7
references.pmid: 16825435
references.citation: Reprod Biomed Online. 2010 Jun;20(6):843-7
references.pmid: 20385510
references.citation: Hum Reprod. 2008 Dec;23(12):2826-34
references.pmid: 18703582
references.citation: Eur J Hum Genet. 2009 May;17(5):611-9
references.pmid: 19092779
references.citation: Hum Mol Genet. 2012 Jan 1;21(1):10-25
references.pmid: 21920939
references.citation: Am J Hum Genet. 2006 Apr;78(4):604-14
references.pmid: 16532391
references.citation: Science. 2002 Jun 21;296(5576):2188-90
references.pmid: 12077406
references.citation: Hormones (Athens). 2008 Jan-Mar;7(1):77-81
references.pmid: 18359747
references.citation: Eur J Hum Genet. 2008 Apr;16(4):453-61
references.pmid: 18197189
references.citation: Nat Genet. 2005 Sep;37(9):1003-7
references.pmid: 16086014
references.citation: Fertil Steril. 2008 Nov;90(5):1662-73
references.pmid: 18163998
references.citation: Fertil Steril. 2009 Feb;91(2):305-15
references.pmid: 19201275
references.citation: Acta Paediatr. 2005 Aug;94(8):1163-5
references.pmid: 16188870
references.citation: Hum Reprod. 2012 Aug;27(8):2541-8
references.pmid: 22674207
references.citation: J Med Genet. 1999 Nov;36(11):837-42
references.pmid: 10544228
references.citation: J Assist Reprod Genet. 2007 Apr;24(4):131-6
references.pmid: 17450433