Sonographic findings in Beckwith–Wiedemann syndrome related to <i>H19</i> hypermethylation

Caignec, C. Le; Gicquel, Christine; Gubler, Marie–Claire; Guyot, C.; You, Mingcong; Laurent, Audrey; Joubert, Madeleine; Winer, Norbert; David, Albert; Rival, Jean-Marie

doi:10.1002/pd.818

Cited by 9 publications

(5 citation statements)

References 33 publications

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“…Twenty-one patients were diagnosed with BWS. As reported previously (36), one of them was diagnosed during fetal life when an ultrasound scan revealed bilateral enlarged echogenic kidneys and macrosomia. After genetic counseling, the parents decided to have the pregnancy terminated.…”

Section: Patientssupporting

confidence: 53%

Analysis of the IGF2/H19 imprinting control region uncovers new genetic defects, including mutations of OCT-binding sequences, in patients with 11p15 fetal growth disorders

Demars

Shmela

Rossignol

et al. 2009

Human Molecular Genetics

109

100

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The imprinted expression of the IGF2 and H19 genes is controlled by the imprinting control region 1 (ICR1) located at chromosome 11p15.5. This methylation-sensitive chromatin insulator works by binding the zinc-finger protein CTCF in a parent-specific manner. DNA methylation defects involving the ICR1 H19/IGF2 domain result in two growth disorders with opposite phenotypes: an overgrowth disorder, the Beckwith-Wiedemann syndrome (maternal ICR1 gain of methylation in 10% of BWS cases) and a growth retardation disorder, the Silver-Russell syndrome (paternal ICR1 loss of methylation in 60% of SRS cases). Although a few deletions removing part of ICR1 have been described in some familial BWS cases, little information is available regarding the mechanism of ICR1 DNA methylation defects. We investigated the CTCF gene and the ICR1 domain in 21 BWS patients with ICR1 gain of methylation and 16 SRS patients with ICR1 loss of methylation. We identified four constitutional ICR1 genetic defects in BWS patients, including a familial case. Three of those defects are newly identified imprinting defects consisting of small deletions and a single mutation, which do not involve one of the CTCF binding sites. Moreover, two of those defects affect OCT-binding sequences which are suggested to maintain the unmethylated state of the maternal allele. A single-nucleotide variation was identified in a SRS patient. Our data extends the spectrum of constitutive genetic ICR1 abnormalities and suggests that extensive and accurate analysis of ICR1 is required for appropriate genetic counseling in BWS patients with ICR1 gain of methylation.

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Section: Patientssupporting

confidence: 53%

Analysis of the IGF2/H19 imprinting control region uncovers new genetic defects, including mutations of OCT-binding sequences, in patients with 11p15 fetal growth disorders

Demars

Shmela

Rossignol

et al. 2009

Human Molecular Genetics

109

100

View full text Add to dashboard Cite

show abstract

“…The most commonly described sonographic findings are included in Table 1. (Williams et al ., 2005, Cohen, 2005, Le Caignec et al ., 2004, Fremond et al ., 1997). A targeted ultrasound examination is recommended to evaluate for body asymmetry, abdominal wall defects, renal and cardiac anomalies, macroglossia, adrenomegaly, and an enlarged pancreas (Williams et al ., 2005).…”

Section: Considerations In the Differential Diagnosismentioning

confidence: 99%

Genetic considerations in the prenatal diagnosis of overgrowth syndromes

Vora

Bianchi

2009

Prenatal Diagnosis

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Large (>90%) for gestational age (LGA) fetuses are usually identified incidentally. Detection of the LGA fetus should first prompt the provider to rule out incorrect dates and maternal diabetes. Once this is done, consideration should be given to certain overgrowth syndromes, especially if anomalies are present. The overgrowth syndromes have significant clinical and molecular overlap, and are associated with developmental delay, tumors, and other anomalies. Although genetic causes of overgrowth are considered postnatally, they are infrequently diagnosed prenatally. Here, we review prenatal sonographic findings in fetal overgrowth syndromes, including Pallister-Killian, Beckwith-Wiedemann, Sotos, Perlman, and Simpson-Golabi-Behmel. We also discuss prenatal diagnosis options and recurrence risks.

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“…A total of 166 BWS patients with prenatal features were reported, including the 3 cases present in this study, 50 fetal BWS [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ], and two cohorts of patients that include 24 [ 48 ] and 89 BWS cases [ 49 ], respectively ( Table S1 ). BWS was diagnosed prenatally in 56 fetuses, of which outcomes were available in 31 cases (55.4%; 31/56), consisting of 16 live births (51.6%; 16/31), 14 TOP (45.2%; 14/31), and 1 of in-utero demise (3.2%; 1/31) ( Table S1 ).…”

Section: Resultsmentioning

confidence: 99%

Proposal for Practical Approach in Prenatal Diagnosis of Beckwith–Wiedemann Syndrome and Review of the Literature

Chen

et al. 2022

Diagnostics

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Background: Beckwith–Wiedemann syndrome (BWS) is a phenotypically and genetically heterogeneous disorder associated with epigenetic/genetic aberrations on chromosome 11p15.4p15.5. There is no consensus criterion for prenatal diagnosis of BWS. Methods: Three BWS patients with their clinical histories, prenatal ultrasonographic features, and results of molecular diagnosis were presented. Likewise, by incorporating the findings of our cases and literature review, the phenotypic spectrum and genotype–phenotype correlations of fetal BWS were summarized, and a practical approach in prenatal diagnosis of BWS was proposed. Results: A total of 166 BWS cases with prenatal features were included for analysis. Common fetal features include abdominal wall defects (42.8%), polyhydramnios (33.1%), and macrosomia (32.5%). Molecular pathologies include methylation changes in imprinting control region 1 and 2 (ICR1 and ICR2), paternal uniparental disomy of chromosome 11p15.5, copy number change involving 11p15, etc. Some genotype–phenotype correlations were observed. However, the broad phenotypic spectrum but limited features manifested by affected fetuses rendering ultrasonographic diagnosis not easy. Conclusions: Molecular tests are used for prenatal diagnosis of BWS suspected by ultrasonography. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) is recommended as the first-line molecular tool because it simultaneously detects ICR1/ICR2 methylation statuses and copy numbers that solve the majority of clinical cases in the prenatal scenario.

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Sonographic findings in Beckwith–Wiedemann syndrome related to H19 hypermethylation

Cited by 9 publications

References 33 publications

Analysis of the IGF2/H19 imprinting control region uncovers new genetic defects, including mutations of OCT-binding sequences, in patients with 11p15 fetal growth disorders

Analysis of the IGF2/H19 imprinting control region uncovers new genetic defects, including mutations of OCT-binding sequences, in patients with 11p15 fetal growth disorders

Genetic considerations in the prenatal diagnosis of overgrowth syndromes

Proposal for Practical Approach in Prenatal Diagnosis of Beckwith–Wiedemann Syndrome and Review of the Literature

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