Wiedemann-Beckwith syndrome: presentation of clinical and cytogenetic data on 22 new cases and review of the literature

Pettenati, Mark J.; Haines, Jonathan L.; Higgins, Rodney R.; Wappner, Rebecca S.; Palmer, Catherine G.; Weaver, David D.

doi:10.1007/bf00282078

Cited by 287 publications

(202 citation statements)

References 44 publications

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“…One was a Wilms tumor with a fatal outcome and the other an adrenal adenoma. This is a much higher rate of association than in BWS cases in general, although it is similar to the prevalence in those with BWS who also have hemihypertrophy [1]. Five of the six cases were in male infants, with no obvious explanation for this male preponderance, as the reported prevalence of BWS in males and females is not significantly different [1].…”

Section: Resultssupporting

confidence: 51%

Benign hemorrhagic adrenocortical macrocysts in Beckwith-Wiedemann syndrome.

McCauley¹,

Beckwith²,

Elias³

et al. 1991

American Journal of Roentgenology

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Section: Resultssupporting

confidence: 51%

Benign hemorrhagic adrenocortical macrocysts in Beckwith-Wiedemann syndrome.

McCauley¹,

Beckwith²,

Elias³

et al. 1991

American Journal of Roentgenology

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“…These documents were approved by the Institutional Review Board. For the purposes of the study, we defined a patient as having BWS if a clinical diagnosis of BWS had been made by a physician and the patient had at least two of the five most common features associated with BWS (14): [1] macroglossia, [2] birth weight greater than 90 percentile (15,16), [3] hypoglycemia in the first month of life, [4] ear creases or ear pits, and [5] midline abdominal wall defects (e.g., omphalocele, diastasis recti, and umbilical hernia). All positive phenotypic features were diagnosed by a physician and were documented in the questionnaire.…”

Section: Methodsmentioning

confidence: 99%

Association between Beckwith-Wiedemann syndrome and assisted reproductive technology: A case series of 19 patients

Chang¹,

Moley²,

Wangler

et al. 2005

Fertility and Sterility

213

141

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Objective-An association between assisted reproductive technique (ART) and specific imprinting mutations, such as Beckwith-Wiedemann syndrome (BWS), has recently been documented. Based on experiments in farm animals that demonstrated an association between alterations in culture media during ART and large offspring syndrome, we hypothesized that the culture media could be implicated as a common factor among the children with BWS conceived after ART. Design-Retrospective case series.Setting-Registry from Academic Medical Center. Patient(s)-Nineteen children born after ART were identified within the registry.Main Outcome Measure(s)-Demographics of patients, type of ART, culture media, IVF parameters.Result(s)-Twelve of the 19 medical records from the reproductive endocrine centers were successfully obtained. Ten of 12 mothers of children with BWS had IVF, but no single, consistent culture media was used in this group. Half of the patients underwent IVF with intracytoplasmic sperm injection (ICSI; n = 5), whereas the other half had routine IVF. One child was conceived through clomiphene citrate (CC) stimulation and artificial insemination, whereas another patient conceived through gonadotropin stimulation with intrauterine insemination (IUI). The gonadotropin dosage and quantity of embryos transferred also varied significantly. The only consistent finding was that all 12 women received some type of ovarian stimulation medication. An association between assisted reproductive technology (ART) and congenital malformation syndromes associated with imprinting defects has recently been documented (4, 5). Three groups have reported an increased rate of ART conceptions among children with BWS (5-7). Only one of these studies prospectively determined the incidence of ART in children with BWS (5). Combined data from two studies suggest that approximately 4% of the children with BWS were born after ART (5, 7). HHS Public AccessAngelman syndrome, a congenital malformation syndrome characterized by mental retardation, motor defects, and lack of speech is associated with imprinting abnormalities and ART (MIM 105830) (4). Angelman syndrome occurs in children with imprinting abnormalities of a gene cluster on chromosome 15 resulting in a loss of function of the maternal allele of ubiquitin-protein ligase E3A (UBE3A) (MIM 601623) (8). Three children with Angelman syndrome have been reported who were conceived after IVF with intracytoplasmic sperm injection (ICSI) lending further support for the association between congenital malformation syndromes with imprinting mutations and ART (4, 9).Results from two embryo experiments conducted in cows and mice led to this proposed study. First, Thompson et al. (10) demonstrated that they could decrease the frequency of large offspring syndrome (LOS) in farm animals after ART by changing the protein supplementation in the culture medium from sera to albumin and amino acids. The LOS refers to a syndrome that occurs after ART in sheep and cows and is associated with macrosomia, polyhyd...

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“…1,2 This disease is a multigenic disorder caused by dysregulation of the expression of imprinted genes in the 11p15 chromosomal region. It may involve uniparental disomy (UPD), maternally inherited translocations, trisomy with paternal duplication, loss of imprinting (LOI) of the IGF2 gene, a paternally expressed autocrine growth factor, hypermethylation of the H19 gene, a maternally expressed untranslated RNA and mutation in the CDKN1C gene, a maternally expressed cell-cycle regulator (review in 3 ).…”

Section: Introductionmentioning

confidence: 99%

Analysis of the methylation status of the KCNQ1OT and H19 genes in leukocyte DNA for the diagnosis and prognosis of Beckwith–Wiedemann syndrome

et al. 2001

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Beckwith ± Wiedemann syndrome (BWS) is an overgrowth disorder involving developmental abnormalities, tissue and organ hyperplasia and an increased risk of embryonal tumours (most commonly Wilms tumour). This multigenic disorder is caused by dysregulation of the expression of imprinted genes in the 11p15 chromosomal region. Molecular diagnosis of BWS is currently difficult, mostly due to the large spectrum of genetic and epigenetic abnormalities. The other difficulty in managing BWS is the identification of patients at risk of tumour. An imprinted antisense transcript within KCNQ1, called KCNQ1OT (also known as LIT1), was recently shown to be normally expressed from the paternal allele. A loss of imprinting of the KCNQ1OT gene, associated with the loss of maternal allele-specific methylation of the differentially methylated region KvDMR1 has been described in BWS patients. The principal aim of this study was to evaluate the usefulness of KvDMR1 methylation analysis of leukocyte DNA for the diagnosis of BWS. The allelic status of the 11p15 region and the methylation status of the KCNQ1OT and H19 genes were investigated in leukocyte DNA from 97 patients referred for BWS and classified into two groups according to clinical data: complete BWS (CBWS) (n=61) and incomplete BWS (IBWS) (n=36). Fifty-eight (60%) patients (39/61 CBWS and 19/36 IBWS) displayed abnormal demethylation of KvDMR1. In 11 of the 56 informative cases, demethylation of KvDMR1 was related to 11p15 uniparental disomy (UPD) (nine CBWS and two IBWS). Thirteen of the 39 patients with normal methylation of KvDMR1 displayed hypermethylation of the H19 gene. These 13 patients included two siblings with 11p15 trisomy. These results show that analysis of the methylation status of KvDMR1 and the H19 gene in leukocyte DNA is useful in the diagnosis of 11p15-related overgrowth syndromes, resulting in the diagnosis of BWS in more than 70% of investigated patients. We also evaluated clinical and molecular features as prognostic factors for tumour and showed that mosaicism for 11p15 UPD and hypermethylation of the H19 gene in blood cells were associated with an increased risk of tumour.

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Wiedemann-Beckwith syndrome: presentation of clinical and cytogenetic data on 22 new cases and review of the literature

Cited by 287 publications

References 44 publications

Benign hemorrhagic adrenocortical macrocysts in Beckwith-Wiedemann syndrome.

Benign hemorrhagic adrenocortical macrocysts in Beckwith-Wiedemann syndrome.

Association between Beckwith-Wiedemann syndrome and assisted reproductive technology: A case series of 19 patients

Analysis of the methylation status of the KCNQ1OT and H19 genes in leukocyte DNA for the diagnosis and prognosis of Beckwith–Wiedemann syndrome

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