Beckwith-Wiedemann Syndrome and IVF: A Case-Control Study

Halliday, Jane; Oke, Kay; Breheny, Sue; Algar, Elizabeth; Amor, David J.

doi:10.1086/423902

Cited by 347 publications

(225 citation statements)

References 21 publications

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“…It is well know that BWS is more common among patients conceived by artificial reproduction technique; [36][37][38] we encountered a 4.4% prevalence of this phenomenon, confirming data from previous reports and showing a higher prevalence than that reported in the Italian population (1.7%). 39 As concerns tumor risk, the overall prevalence of cancer approximates 8%, consistent with other studies.…”

Section: Phenotypes In Beckwith-wiedemann Syndromesupporting

confidence: 91%

(Epi)genotype–phenotype correlations in Beckwith–Wiedemann syndrome

et al. 2015

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Beckwith-Wiedemann syndrome (BWS) is characterized by cancer predisposition, overgrowth and highly variable association of macroglossia, abdominal wall defects, nephrourological anomalies, nevus flammeus, ear malformations, hypoglycemia, hemihyperplasia, and organomegaly. BWS molecular defects, causing alteration of expression or activity of the genes regulated by two imprinting centres (IC) in the 11p15 chromosomal region, are also heterogeneous. In this paper we define (epi)genotype-phenotype correlations in molecularly confirmed BWS patients. The characteristics of 318 BWS patients with proven molecular defect were compared among the main four molecular subclasses: IC2 loss of methylation (IC2-LoM, n = 190), IC1 gain of methylation (IC1-GoM, n = 31), chromosome 11p15 paternal uniparental disomy (UPD, n = 87), and cyclin-dependent kinase inhibitor 1C gene (CDKN1C) variants (n = 10). A characteristic growth pattern was found in each group; neonatal macrosomia was almost constant in IC1-GoM, postnatal overgrowth in IC2-LoM, and hemihyperplasia more common in UPD (Po0.001). Exomphalos was more common in IC2/CDKN1C patients (Po0.001). Renal defects were typical of UPD/IC1 patients, uretheral malformations of IC1-GoM cases (Po0.001). Ear anomalies and nevus flammeus were associated with IC2/CDKN1C genotype (Po0.001). Macroglossia was less common among UPD patients (Po0.001). Wilms' tumor was associated with IC1-GoM or UPD and never observed in IC2-LoM patients (Po0.001). Hepatoblastoma occurred only in UPD cases. Cancer risk was lower in IC2/CDKN1C, intermediate in UPD, and very high in IC1 cases (P = 0.009).In conclusion, (epi)genotype-phenotype correlations define four different phenotypic BWS profiles with some degree of clinical overlap. These observations impact clinical care allowing to move toward (epi) genotype-based follow-up and cancer screening.

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Section: Phenotypes In Beckwith-wiedemann Syndromesupporting

confidence: 91%

(Epi)genotype–phenotype correlations in Beckwith–Wiedemann syndrome

et al. 2015

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“…89,90 A number of studies report that BWS and AS cases are overrepresented in children born through ART. 42,[91][92][93][94][95] However, other studies did not find evidence for increased risk for these diseases, 96,97 and the relationship between ART and imprinting disorders remains to be established. 98,99 Recently, it was reported that the expression state of the imprinted Dlk1-Dio3 cluster on mouse chromosome 12 is often altered in iPS cells.…”

Section: Molar Pregnancy Infertility Assisted Reproductive Technolomentioning

confidence: 96%

Genomic imprinting and its relevance to congenital disease, infertility, molar pregnancy and induced pluripotent stem cell

Tomizawa

Sasaki

2012

J Hum Genet

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Genomic imprinting is an epigenetic gene-marking phenomenon that occurs in the germline, whereby genes are expressed from only one of the two parental copies in embryos and adults. Imprinting is essential for normal mammalian development and its disruption can cause various developmental defects and diseases. The process of imprinting in the germline involves DNA methylation of the imprint control regions (ICRs), and resulting parental-specific methylation imprints are maintained in the zygote and act as the marks controlling imprinted gene expression. Recent studies in mice have revealed new factors involved in imprint establishment during gametogenesis and maintenance during early development. Clinical studies have identified cases of imprinting disorders where involvement of factors shared by multiple ICRs for establishment or maintenance is suspected. These include Beckwith-Wiedemann syndrome, transient neonatal diabetes, Silver-Russell syndrome and others. More severe disruptions can lead to recurrent molar pregnancy, miscarriage or infertility. Imprinting defects may also occur during assisted reproductive technology or cell reprogramming. In this review, we summarize our current knowledge on the mechanisms of imprint establishment and maintenance, and discuss the relationship with various human disorders.

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“…46 It is clear that, in the presence of IVF and ICSI, there is an increased risk of the ones caused primarily by epigenetic errors rather than chromosomal problems, such as the case with Beckwith-Weideman syndrome. 47,48 The risk, albeit small, is important because it demonstrates the possibility of other, as yet unidentified, adverse outcomes due to epigenetic errors. Importantly in the context of this review, it does not appear to be an ICSI specific, and therefore, potentially male infertility-related, problem.…”

Section: Overall Defectsmentioning

confidence: 99%

Outcomes for offspring of men having ICSI for male factor infertility

Halliday¹

2011

Asian J Androl

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Since the introduction of intracytoplasmic sperm injection (ICSI) using single sperm isolated from testicular tissue in men with obstructive and non-obstructive azoospermia, or using ejaculated sperm in those with poor semen quality, there have been concerns that this might have adverse effects on the offspring compared to conventional in vitro fertilisation (IVF) and natural conceptions. ICSI is done for reasons other than male factor infertility, and on the whole has not been shown to have any more negative effects than those seen with IVF. There have however, been very few studies of ICSI with a focus on, or large enough numbers to examine, the specific outcomes associated with male factor infertility. From the limited information available in relation to the source of the sperm and aetiology of infertility in the presence of ICSI, there appears to be no increased risk of congenital malformations. There is, however, a small increase in both de novo and inherited chromosome abnormalities. In terms of growth and neurodevelopment, there are very few studies, and so far, no adverse outcomes have been found in young children whose fathers have a sperm defect. The origin of the sperm used in ICSI does not have a major influence on the early life outcomes for the offspring, but transgenerational and epigenetic effects remain unknown. When the male factor infertility is known or thought to be due to a Y-chromosome deletion, this information should be given to the young male offspring at a time that will ensure his own reproductive health and plans are optimized.

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Beckwith-Wiedemann Syndrome and IVF: A Case-Control Study

Abstract: A family of human Y chromosomes has dispersed throughout northern Eurasia despite a 1.8-Mb deletion in the azoospermia factor c region. Gen

Cited by 347 publications

References 21 publications

(Epi)genotype–phenotype correlations in Beckwith–Wiedemann syndrome

(Epi)genotype–phenotype correlations in Beckwith–Wiedemann syndrome

Genomic imprinting and its relevance to congenital disease, infertility, molar pregnancy and induced pluripotent stem cell

Outcomes for offspring of men having ICSI for male factor infertility

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