Association of In Vitro Fertilization with Beckwith-Wiedemann Syndrome and Epigenetic Alterations of LIT1 and H19

• Published in: American journal of human genetics 2003-01, Vol.72 (1), p.156-160
• Main Authors: DeBaun, Michael R., Niemitz, Emily L., Feinberg, Andrew P.
• Format: Article
• Language: English
• Subjects: Adult; Beckwith-Wiedemann Syndrome - etiology; Beckwith-Wiedemann Syndrome - genetics; Beckwith-Wiedemann Syndrome - pathology; Bioethics; Biological and medical sciences; Child; Complex syndromes; CpG Islands - genetics; DNA Methylation; Female; Fertilization in Vitro - adverse effects; Genomic Imprinting - genetics; Humans; Male; Medical genetics; Medical sciences; Membrane Proteins; Molecular Sequence Data; Phenotype; Potassium Channels, Voltage-Gated; RNA, Long Noncoding; RNA, Untranslated - genetics
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/346031

Recent data in humans and animals suggest that assisted reproductive technology (ART) might affect the epigenetics of early embryogenesis and might cause birth defects. We report the first evidence, to our knowledge, that ART is associated with a human overgrowth syndrome—namely, Beckwith-Wiedemann syndrome (BWS). In a prospective study, the prevalence of ART was 4.6% (3 of 65), versus the background rate of 0.8% in the United States. A total of seven children with BWS were born after ART—five of whom were conceived after intracytoplasmic sperm injection. Molecular studies of six of the children indicate that five of the six have specific epigenetic alterations associated with BWS—four at LIT1 and one at both LIT1 and H19. We discuss the implications of our finding that ART is associated with human overgrowth, similar to the large offspring syndrome reported in ruminants.