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Clinical Case Reports Jul 2021Beckwith-Wiedemann syndrome is a complex multisystem disorder that requires collaboration of medical and dental teamfor its diagnosis and management. We present a dental...
Beckwith-Wiedemann syndrome is a complex multisystem disorder that requires collaboration of medical and dental teamfor its diagnosis and management. We present a dental overview and an update of the clinical and molecular diagnoses of Beckwith-Wiedemann syndrome and its management with emphasis on macroglossia.
PubMed: 34257987
DOI: 10.1002/ccr3.4479 -
American Journal of Medical Genetics.... Jul 2019Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder with a heterogeneous phenotypic spectrum. There is an increased prevalence of monozygotic twinning in BWS....
Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder with a heterogeneous phenotypic spectrum. There is an increased prevalence of monozygotic twinning in BWS. Given the epigenetic nature and phenotypic spectrum that defines BWS, twins are often discordant for clinical features, and clinicians are faced with the challenge of diagnosing and managing these twins. We present a cohort of multiple pregnancies in which one or more child from each pregnancy was diagnosed with BWS. We conducted a chart review of monochorionic and dichorionic gestations. Clinical scores for monochorionic twins demonstrated phenotypic discordance between the proband and twin. Based on linear regression analysis, a higher clinical score in the proband correlated with larger phenotypic discordance between twin siblings. Despite phenotypic discordance, however, we observed a consistent additive clinical score for a pregnancy (proband's plus twin's scores from a pregnancy). This idea of a finite degree of affectedness for a pregnancy implies a finite number of epigenetically affected cells. This further corroborates the idea that timing of monozygotic monochorionic twinning correlates with the disruption of establishment and/or maintenance of imprinting. The difference in clinical score between a proband and their twin may be due to diffused mosaicism, whereby there is an asymmetric distribution of affected cells among the multiple fetuses in a monozygotic monochorionic pregnancy, leading to a spectrum of variably affected phenotypes. Based on these findings, we recommend an algorithm for a conservative approach to clinically evaluate all children in a monozygotic multiple gestation affected by BWS.
Topics: Algorithms; Beckwith-Wiedemann Syndrome; Cohort Studies; DNA Methylation; Disease Management; Diseases in Twins; Female; Genomic Imprinting; Humans; Infant; Male; Mosaicism; Phenotype; Pregnancy; Severity of Illness Index; Twins, Dizygotic; Twins, Monozygotic
PubMed: 31067005
DOI: 10.1002/ajmg.a.61164 -
Molecular Cytogenetics Mar 2021Molecular genetic testing for the 11p15-associated imprinting disorder Beckwith-Wiedemann syndrome (BWS) is challenging because of the molecular heterogeneity and...
BACKGROUND
Molecular genetic testing for the 11p15-associated imprinting disorder Beckwith-Wiedemann syndrome (BWS) is challenging because of the molecular heterogeneity and complexity of the affected imprinted regions. An integrated molecular approach to analyze the epigenetic-genetic alterations is required for accurate diagnosis of BWS.
CASE PRESENTATION
We reported a Chinese case with BWS detected by SNP array analysis and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). The genetic analysis showed a de novo duplication of 24 Mb at 11p15.5p14.3 is much longer than ever reported. MS-MLPA showed copy number changes with a peak height ratio value of 1.5 (three copies) at 11p15. The duplication of paternal origin with increase of methylation index of 0.68 at H19 and decreased methylation index of 0.37 at KCNQ1OT1.
CONCLUSION
Combined chromosome microarray analysis and methylation profiling provided reliable diagnosis for this paternally derived duplication of BWS. The phenotype associated with 11p15 duplications depends on the size, genetic content, parental inheritance and imprinting status. Identification of these rare duplications is crucial for genetic counselling.
PubMed: 33658067
DOI: 10.1186/s13039-021-00532-7 -
Global Medical Genetics Mar 2021Assisted reproductive technology (ART) is a broad field in infertility that encompasses different types of treatments. These revolutionary treatment methods aimed to aid... (Review)
Review
Assisted reproductive technology (ART) is a broad field in infertility that encompasses different types of treatments. These revolutionary treatment methods aimed to aid infertile or subfertile couples. Treatment was expanded exponentially, as 1 to 3% of the births worldwide takes place with ART procedures. However, treatment is not flawless. Gametes and embryos are exposed to different chemicals and stress through treatment, which leads to disturbance in proper embryo development and results in prenatal and congenital anomalies. When compared with in-vivo development of gametes and preimplantation embryos in mice, in-vitro conditions during ART treatments have been suggested to disturb the gene expression levels, especially imprinted genes. Therefore, ART has been suggested to be associated with increased incidences of different imprinting disorders such as Beckwith-Wiedemann syndrome, Angelman syndrome, and Silver-Russell syndrome, as proved by different case reports and studies. This literature review aims to explain the association of imprinting disorders with this revolutionary treatment procedure.
PubMed: 33748817
DOI: 10.1055/s-0041-1723085 -
Gaceta Medica de Mexico 2022Epigenetic and genomic imprinting alterations of the 11p15.5 region cause excessive or deficient growth, which result in Beckwith-Wiedemann syndrome (BWS) or...
INTRODUCTION
Epigenetic and genomic imprinting alterations of the 11p15.5 region cause excessive or deficient growth, which result in Beckwith-Wiedemann syndrome (BWS) or Silver-Russell syndrome (SRS), respectively.
OBJECTIVE
To evaluate the methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) methylation analysis technique in the diagnosis of BWS and SRS.
METHODS
11p15.5 methylation and variants were evaluated in patients with clinical diagnosis of BWS and SRS using the MS-MLPA technique in peripheral blood DNA.
RESULTS
Paternal uniparental disomy and loss of maternal IC2 methylation were identified in two patients with BWS who had omphalocele and macroglossia, respectively. Paternal IC1hypomethylation was recorded in two patients with SRS of classic phenotype.
CONCLUSIONS
Adequate genotype-phenotype correlation was observed with the methylation defects that were identified, which confirms the usefulness of MLPA as a first-line study in patients diagnosed with BWS and SRS.
Topics: Humans; Silver-Russell Syndrome; Beckwith-Wiedemann Syndrome; Multiplex Polymerase Chain Reaction; DNA Methylation; Genomic Imprinting
PubMed: 36256576
DOI: 10.24875/GMM.M22000673 -
Genetics in Medicine : Official Journal... Nov 2019Beckwith-Wiedemann syndrome (BWS) is a human genomic imprinting disorder characterized by lateralized overgrowth, macroglossia, abdominal wall defects, congenital...
PURPOSE
Beckwith-Wiedemann syndrome (BWS) is a human genomic imprinting disorder characterized by lateralized overgrowth, macroglossia, abdominal wall defects, congenital hyperinsulinism, and predisposition to embryonal tumors. One of the molecular etiologies underlying BWS is paternal uniparental isodisomy of chromosome 11p15.5 (pUPD11). About 8% of pUPD11 cases are due to genome-wide paternal uniparental isodisomy (GWpUPD). About 30 cases of live-born patients with GWpUPD have been described, most of whom were mosaic and female. We present male patients with BWS due to GWpUPD, elucidate the underlying mechanism, and make recommendations for management.
METHODS
Three male patients with GWpUPD underwent clinical and molecular evaluation by single-nucleotide polymorphism (SNP) microarrays in different tissues. Previously published cases of GWpUPD were reviewed.
RESULTS
SNP microarray demonstrated a GWpUPD cell population with sex chromosomes XX and biparental cell population with sex chromosomes XY, consistent with dispermic androgenetic chimerism.
CONCLUSION
SNP microarray is necessary to distinguish GWpUPD cases and the underlying mechanisms. The percentage of GWpUPD cell population within a specific tissue type correlated with the amount of tissue dysplasia. Males with BWS due to GWpUPD are important to distinguish from other molecular etiologies because the mechanism indicates risk for germ cell tumors and autosomal recessive diseases in addition to other BWS features.
Topics: Beckwith-Wiedemann Syndrome; Chimerism; Chromosomes, Human, Pair 11; DNA Methylation; Genomic Imprinting; Genotype; Humans; Infant; Infant, Newborn; Male; Mosaicism; Phenotype; Polymorphism, Single Nucleotide; Uniparental Disomy
PubMed: 31147633
DOI: 10.1038/s41436-019-0551-9 -
International Journal of Environmental... Feb 2022Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder caused by various (epi)genetic alterations affecting the expression of genes on chromosome 11p15....
Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder caused by various (epi)genetic alterations affecting the expression of genes on chromosome 11p15. Cardinal features include abdominal wall defects, macroglossia, and cancer predisposition. Several (epi)genotype-phenotype associations were described so far, but specific studies on the evolution over time of maxillo-facial phenotype in the molecular subtypes still are scanty. The aim of this cross-sectional study was to associate maxillo-facial morphology and growth pattern with genoype in 25 Caucasian children with BWS and macroglossia. Twelve patients experienced a loss of metilation at imprinting center 2 (IC2-LoM), five had mosaic paternal uniparental isodisomy of chromosome 11 (UPD(11)pat), and eight were negative. A more marked tongue enlargement was detected in patients with IC2-LoM and negative genotype, while UPD(11)pat children showed mild macroglossia ( = 0.048). A cluster analysis did not demonstrate any specific relationship between (epi)genotype and maxillo-facial phenotype, but separated BWS patients based on their cephalometric characteristics. Children with IC2-LoM or negative genotype displayed hyperdivergence values > 30°, clockwise growth tendency, and skeletal class II into the same cluster. They had a negative prognostic score. These preliminary data suggest the need for developing individualized protocols for early monitoring of the craniofacial growth in such patients.
Topics: Beckwith-Wiedemann Syndrome; Cross-Sectional Studies; DNA Methylation; Genetic Association Studies; Genomic Imprinting; Humans; Male; Phenotype
PubMed: 35206635
DOI: 10.3390/ijerph19042448 -
Children (Basel, Switzerland) Apr 2022Beckwith-Wiedemann syndrome (BWS) is a rare overgrowth disease and is not usually associated with intellectual delay. Living with a chronic illness condition such as...
Beckwith-Wiedemann syndrome (BWS) is a rare overgrowth disease and is not usually associated with intellectual delay. Living with a chronic illness condition such as BWS, however, might affect emotional-behavioral functioning and psychosocial development. To investigate this issue, parents of 30 children with BWS between 1.5 and 6 years old compiled standardized questionnaires assessing the presence of emotional-behavioral and developmental problems. The group mean scores in each scale of behavioral problems fell within the average range. Nevertheless, 23% of the sample presented scores beyond the risk threshold for social withdrawal. As regards psychomotor development, a lower mean score was reliable in the social domain compared to other developmental scales, and in the gross-motor compared to fine-motor functions. Moreover, scores in the at-risk band were reliable in almost half of the children for social development. Notably, older age was overall associated with higher emotional-behavioral and developmental difficulties, while no other socio-demographic or clinical variables accounted for the scores obtained in the questionnaires. These findings ask for a wider consideration by health and educational professionals of the psychosocial functioning of children with BWS, so as to early detect at-risk conditions and eventually promote adequate interventions.
PubMed: 35455595
DOI: 10.3390/children9040551 -
Children (Basel, Switzerland) Mar 2024The study's aim was to determine the prevalence of depression and anxiety in children with Beckwith-Wiedemann syndrome (BWS) and their effects on social relationships...
The study's aim was to determine the prevalence of depression and anxiety in children with Beckwith-Wiedemann syndrome (BWS) and their effects on social relationships and family acceptance. The Pediatric Symptom Checklist-35 items (PSC-35), Screen for Child Anxiety Related Emotional Disorders (SCARED), and the Vineland Adaptive Behavior Scale Second Edition (VABS-II) were administered to the children. The parental Acceptance Rejection/Control Questionnaire (PARQ/Control) and Zarit Burden Inventory (ZBI) were administered to parents. In total, 6 patients and 10 parents were included. Patients showed a significant presence of internalizing behavior in PSC-35 (mean, 7.66 ± 3.67), anxiety symptoms (SCARED: mean, 46.33 ± 17.50) and socialization difficulties (mean, 90.83 ± 10.09). Parents reported a perceived good acceptance (mean, 56.33 ± 1.03) and a moderate control (mean, 24.17 ± 1.83), but the burden level was ranked moderate to severe (mean, 59.33 ± 16.78). It was found that the severity of the burden level reported by parents was related to internalizing behavior (OR = 2.000; 95% CI = 0.479-3.521; = 0.022) and anxiety symptoms (SCARED total score: OR = 3.000; 95% CI = 1.479-4.521; = 0.005) of children. During psychological counseling in the context of BWS treatment, it is important to identify specific resources that can support patients and families in dealing with stress and identify any critical areas that could hinder the adaptation process.
PubMed: 38539377
DOI: 10.3390/children11030342 -
Annals of Medicine and Surgery (2012) Apr 2021Wilms' tumor (WT) is the most frequently occurring paediatric renal tumor and is one of the most treatment-responsive tumors. A tumor-suppressor gene and other genetic... (Review)
Review
BACKGROUND
Wilms' tumor (WT) is the most frequently occurring paediatric renal tumor and is one of the most treatment-responsive tumors. A tumor-suppressor gene and other genetic abnormalities have been implicated in its etiology. In addition, patients with many congenital anomalies, such as Beckwith-Wiedemann syndrome, WAGR syndrome and Denys-Drash syndrome, have an increased risk of WT.
METHODS AND RESULTS
Two large collaborative groups - National Wilms Tumor Study Group (NWTSG)/Children's Oncology Group (COG) and The International Society of Paediatric Oncology (SIOP) have laid down the guidelines for standardized treatment of WT, though differing in the diagnostic and therapeutic approach. The major difference in the two guidelines is the timing of surgery: SIOP recommends using preoperative chemotherapy and NWTSG/COG prefers primary surgery before any adjuvant treatments. Both these groups currently aim at intensifying treatment for patients with poor prognosticators while appropriating the therapy to reduce long-term complications for those with favourable prognostic features. As the survival rate has now reached 90%, the primary objectives of the physician are to perform nephron-sparing surgery in selected cases and to reduce the dosage and duration of chemotherapy and radiotherapy in appropriate cases. The purpose of this review is to present current standards of diagnosis and treatment of WT around the world.
CONCLUSION
Further studies in future should be done to highlight the use of chemotherapy and radiotherapy under risk-stratified strategies. Further improvement in survival of these children can only be achieved by increasing awareness, early recognition, appropriate referral, and a multidisciplinary approach.
PubMed: 33747498
DOI: 10.1016/j.amsu.2021.102202