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Cureus Oct 2023Beckwith-Wiedemann syndrome (BWS) is a rare genetic disorder, distinguished by the following characteristics: macrosomia, macroglossia, abdominal wall...
Beckwith-Wiedemann syndrome (BWS) is a rare genetic disorder, distinguished by the following characteristics: macrosomia, macroglossia, abdominal wall deformities such as omphalocele, visceromegaly, hemihypertrophy and elevated risk of developing tumors such as nephroblastoma or hepatoblastoma. A 2.5-year-old female patient came to the Department of Pediatric and Preventive Dentistry with a complaint of abnormally large tongue along with difficulty in swallowing and slurred speech. On clinical examination, the built of the patient was greater than normal. Intraoral examination revealed an enlarged tongue that led to the inability to close her mouth. Preliminary tests like blood tests, ECG, etc., were done before proceeding further to correct the enlarged tongue surgically under general anesthesia. The patient was intubated nasally, and a keyhole incision pattern was marked on the dorsum of the tongue at the central part. Reduction glossectomy was performed using electrocautery and the two parts were thereafter sutured with 5-0 vicryl sutures. The patient was kept under observation for one week and then discharged. Satisfactory healing was observed. Early diagnosis, close monitoring by healthcare specialists, and a thorough treatment plan that includes speech therapy, food support, and dental care can help manage the issues associated with BWS macroglossia.
PubMed: 37933371
DOI: 10.7759/cureus.46579 -
Nature Communications Nov 2023Pediatric liver tumors are very rare tumors with the most common diagnosis being hepatoblastoma. While hepatoblastomas are predominantly sporadic, around 15% of cases...
Pediatric liver tumors are very rare tumors with the most common diagnosis being hepatoblastoma. While hepatoblastomas are predominantly sporadic, around 15% of cases develop as part of predisposition syndromes such as Beckwith-Wiedemann (11p15.5 locus altered). Here, we identify mosaic genetic alterations of 11p15.5 locus in the liver of hepatoblastoma patients without a clinical diagnosis of Beckwith-Wiedemann syndrome. We do not retrieve these alterations in children with other types of pediatric liver tumors. We show that mosaic 11p15.5 alterations in liver FFPE sections of hepatoblastoma patients display IGF2 overexpression and H19 downregulation together with an alteration of the liver zonation. Moreover, mosaic livers' microenvironment is enriched in extracellular matrix and angiogenesis. Spatial transcriptomics and single-nucleus RNAseq analyses identify a 60-gene signature in 11p15.5 altered hepatocytes. These data provide insights for 11p15.5 mosaicism detection and its functional consequences during the early steps of carcinogenesis.
Topics: Humans; Child; Child, Preschool; Hepatoblastoma; Beckwith-Wiedemann Syndrome; Liver Neoplasms; Mosaicism; DNA Methylation; Genomic Imprinting; Tumor Microenvironment
PubMed: 37932266
DOI: 10.1038/s41467-023-42418-9 -
JCEM Case Reports May 2023Beckwith-Wiedemann syndrome (BWS) is a rare genetic disorder characterized by genetic and epigenetic changes on the chromosome 11p15.5 region, which includes genes that...
Beckwith-Wiedemann syndrome (BWS) is a rare genetic disorder characterized by genetic and epigenetic changes on the chromosome 11p15.5 region, which includes genes that are important for fetal and postnatal growth. Children with BWS have a higher chance of having hypoglycemia, hyperinsulinemia, and malignancies early in life, although hypoglycemia caused by an insulinoma that develops later in life has not been reported. We describe the diagnosis of insulinoma in a 53-year-old man with BWS in this case report. This is the first case report of insulinoma in an adult with this syndrome.
PubMed: 37908580
DOI: 10.1210/jcemcr/luad062 -
JCEM Case Reports Sep 2023Children with hepatoblastoma have an increased incidence of fractures, but data are limited. Previous reports document an average of 4 fractures per child with...
Children with hepatoblastoma have an increased incidence of fractures, but data are limited. Previous reports document an average of 4 fractures per child with hepatoblastoma. We present a severe case of a premature 4-month-old with multiple fractures in the setting of Beckwith-Wiedemann syndrome and hepatoblastoma. Although prematurity is a known risk for metabolic bone disease, it did not entirely explain the severity. Our patient underwent chemotherapy and surgical resection of his hepatoblastoma. Once deemed stable, he received a dose of zoledronic acid (ZA). One month post treatment with ZA, a skeletal survey revealed healing of the rib and femoral fractures and no new fractures. Five months post ZA, the skeletal survey revealed no new fractures and motor development was appropriate. An extensive search revealed scant literature on the rate or cause of pathologic fractures in patients with newly diagnosed hepatoblastoma. A better understanding of fracture risk in this population may guide prevention strategies, screening, and treatment. In our case, prematurity and substantial chronic illness may have compounded the known fracture risk associated with hepatoblastoma and may provide insight into the pathophysiology and prevention of fractures in this setting.
PubMed: 37908208
DOI: 10.1210/jcemcr/luad110 -
Cancers Oct 2023Beckwith-Wiedemann syndrome (BWS) is a genetic imprinting disorder that most commonly presents as overgrowth, macroglossia, abdominal wall defects, lateralized...
Beckwith-Wiedemann syndrome (BWS) is a genetic imprinting disorder that most commonly presents as overgrowth, macroglossia, abdominal wall defects, lateralized overgrowth, and embryonal tumors [...].
PubMed: 37894306
DOI: 10.3390/cancers15204939 -
Children (Basel, Switzerland) Aug 2023Here, we report the perioperative management of a clinical case of a 6 year, 5 month old girl suffering from Beckwith-Wiedemann syndrome undergoing a partial glossectomy...
Here, we report the perioperative management of a clinical case of a 6 year, 5 month old girl suffering from Beckwith-Wiedemann syndrome undergoing a partial glossectomy procedure in a patient with surgical indication for obstructive sleep apnea syndrome (OSAS), difficulty swallowing, feeding, and speech. On surgery day, Clonidine (4 µg/kg) was administered. Following this, a general anesthesia induction was performed by administering Sevoflurane, Fentanyl, continuous intravenous Remifentanil, and lidocaine to the vocal cords, and a rhinotracheal intubation with a size 4.5 tube was carried out. Before starting the procedure, a block of the Lingual Nerve was performed with Levobupivacaine. Analgosedation was maintained with 3% Sevoflurane in air and oxygen (FiO of 40%) and Remifentanil in continuous intravenous infusion at a rate of 0.08-0.15 µg/kg/min. The surgical procedure lasted 2 h and 32 min. At the end of the surgery, the patient was under close observation during the first 72 h. In the pediatric patient with Beckwith-Wiedemann syndrome submitted to major maxillofacial surgery, the difficulty in managing the airways in the preoperative phase during intubation and in the post-operative phase during extubation should be considered.
PubMed: 37761428
DOI: 10.3390/children10091467 -
Italian Journal of Pediatrics Sep 2023Beckwith-Wiedemann syndrome (BWS, OMIM #130,650) is a pediatric overgrowth disorder involving a predisposition to tumor development. Although the clinical management of... (Review)
Review
BACKGROUND
Beckwith-Wiedemann syndrome (BWS, OMIM #130,650) is a pediatric overgrowth disorder involving a predisposition to tumor development. Although the clinical management of affected patients is well established, it is less clear how to handle with the cases of siblings of affected patients, since the prevalence of the condition in twins (1:1000) is ten times higher than in singletones (1:10000).
CASE PRESENTATION
We report the case of a premature twin patient who during her follow-up develops a clinical phenotype compatible with BWS, genetically confirmed in blood. However, the methylation alteration characteristic of the condition was also found in the almost phenotypically normal sibling, making it challening her management.
CONCLUSION
Through our case report we highlight how the diagnosis of BWS can be made without any prenatal suspicion and we propose a review of the literature on how to manage siblings of affected patients in twinning situation.
Topics: Female; Child; Pregnancy; Humans; Beckwith-Wiedemann Syndrome; Genotype; Phenotype; Siblings; Twins
PubMed: 37749604
DOI: 10.1186/s13052-023-01530-8 -
Cancers Aug 2023Embryonic tumors share few recurrent mutations, suggesting that other mechanisms, such as aberrant DNA methylation, play a prominent role in their development. The loss...
Embryonic tumors share few recurrent mutations, suggesting that other mechanisms, such as aberrant DNA methylation, play a prominent role in their development. The loss of imprinting (LOI) at the chromosome region 11p15 is the germline alteration behind Beckwith-Wiedemann syndrome that results in an increased risk of developing several embryonic tumors. This study analyzed the methylome, using EPIC Beadchip arrays from 99 sporadic embryonic tumors. Among these tumors, 46.5% and 14.6% presented alterations at imprinted control regions (ICRs) 1 and 2, respectively. Based on the methylation levels of ICR1 and ICR2, four clusters formed with distinct methylation patterns, mostly for medulloblastomas (ICR1 loss of methylation (LOM)), Wilms tumors, and hepatoblastomas (ICR1 gain of methylation (GOM), with or without ICR2 LOM). To validate the results, the methylation status of 29 cases was assessed with MS-MLPA, and a high level of agreement was found between both methodologies: 93% for ICR1 and 79% for ICR2. The MS-MLPA results indicate that 15 (51.7%) had ICR1 GOM and 11 (37.9%) had ICR2 LOM. To further validate our findings, the ICR1 methylation status was characterized via digital PCR (dPCR) in cell-free DNA (cfDNA) extracted from peripheral blood. At diagnosis, we detected alterations in the methylation levels of ICR1 in 62% of the cases, with an agreement of 76% between the tumor tissue (MS-MLPA) and cfDNA methods. Among the disagreements, the dPCR was able to detect ICR1 methylation level changes presented at heterogeneous levels in the tumor tissue, which were detected only in the methylome analysis. This study highlights the prevalence of 11p15 methylation status in sporadic embryonic tumors, with differences relating to methylation levels (gain or loss), location (ICR1 or ICR2), and tumor types (medulloblastomas, Wilms tumors, and hepatoblastomas).
PubMed: 37686532
DOI: 10.3390/cancers15174256 -
International Journal of Molecular... Aug 2023Beckwith-Wiedemann Syndrome (BWS) is an imprinting disorder, which manifests by overgrowth and predisposition to embryonal tumors. The evidence on the relationship...
Beckwith-Wiedemann Syndrome in Newborn of Mother with HELLP Syndrome/Preeclampsia: An Analysis of Literature and Case Report with Fetal Growth Restriction and Absence of Typical Pathogenic Genetic Variation.
Beckwith-Wiedemann Syndrome (BWS) is an imprinting disorder, which manifests by overgrowth and predisposition to embryonal tumors. The evidence on the relationship between maternal complications such as HELLP (hemolysis, elevated liver enzymes, and low platelet count) and preeclampsia and the development of BWS in offspring is scarce. A comprehensive clinical evaluation, with genetic testing focused on screening for mutations in the CDKN1C gene, which is commonly associated with BWS, was conducted in a newborn diagnosed with BWS born to a mother with a history of preeclampsia and HELLP syndrome. The case study revealed typical clinical manifestations of BWS in the newborn, including hemihyperplasia, macroglossia, midfacial hypoplasia, omphalocele, and hypoglycemia. Surprisingly, the infant also exhibited fetal growth restriction, a finding less commonly observed in BWS cases. Genetic analysis, however, showed no mutations in the gene, which contrasts with the majority of BWS cases. This case report highlights the complex nature of BWS and its potential association with maternal complications such as preeclampsia and HELLP syndrome. The atypical presence of fetal growth restriction in the newborn and the absence of gene mutations have not been reported to date in BWS.
Topics: Female; Pregnancy; Infant; Infant, Newborn; Humans; HELLP Syndrome; Pre-Eclampsia; Beckwith-Wiedemann Syndrome; Fetal Growth Retardation; Mothers; Genetic Variation; Cyclin-Dependent Kinase Inhibitor p57
PubMed: 37686168
DOI: 10.3390/ijms241713360