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Frontiers in Pediatrics 2019Beckwith-Wiedemann syndrome (BWS) is a human genomic imprinting disorder that presents with a wide spectrum of clinical features including overgrowth, abdominal wall... (Review)
Review
Beckwith-Wiedemann syndrome (BWS) is a human genomic imprinting disorder that presents with a wide spectrum of clinical features including overgrowth, abdominal wall defects, macroglossia, neonatal hypoglycemia, and predisposition to embryonal tumors. It is associated with genetic and epigenetic changes on the chromosome 11p15 region, which includes two imprinting control regions. Here we review strategies for diagnosing and managing BWS and delineate commonly used genetic tests to establish a molecular diagnosis of BWS. Recommended first-line testing assesses DNA methylation and copy number variation of the BWS region. Tissue mosaicism can occur in patients with BWS, posing a challenge for genetic testing, and a negative test result does not exclude a diagnosis of BWS. Further testing should analyze additional tissue samples or employ techniques with higher diagnostic yield. Identifying the BWS molecular subtype is valuable for coordinating patient care because of the (epi)genotype-phenotype correlations, including different risks and types of embryonal tumors.
PubMed: 32039119
DOI: 10.3389/fped.2019.00562 -
Frontiers in Endocrinology 2022Adrenocortical carcinoma (ACC) is a rare endocrine malignancy of the adrenal gland with an unfavorable prognosis. It is rare in the pediatric population, with an... (Review)
Review
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy of the adrenal gland with an unfavorable prognosis. It is rare in the pediatric population, with an incidence of 0.2-0.3 patients per million in patients under 20 years old. It is primarily associated with Li-Fraumeni and Beckwith-Wiedemann tumor predisposition syndromes in children. The incidence of pediatric ACC is 10-15fold higher in southern Brazil due to a higher prevalence of mutation associated with Li-Fraumeni syndrome in that population. Current treatment protocols are derived from adult ACC and consist of surgery and/or chemotherapy with etoposide, doxorubicin, and cisplatin (EDP) with mitotane. Limited research has been reported on other treatment modalities for pediatric ACC, including mitotane, pembrolizumab, cabozantinib, and chimeric antigen receptor autologous cell (CAR-T) therapy.
Topics: Adult; Humans; Child; Young Adult; Adrenocortical Carcinoma; Mitotane; Adrenal Cortex Neoplasms; Li-Fraumeni Syndrome
PubMed: 36387865
DOI: 10.3389/fendo.2022.961650 -
Frontiers in Pediatrics 2020Abnormally excessive growth results from perturbation of a complex interplay of genetic, epigenetic, and hormonal factors that orchestrate human growth. Overgrowth... (Review)
Review
Abnormally excessive growth results from perturbation of a complex interplay of genetic, epigenetic, and hormonal factors that orchestrate human growth. Overgrowth syndromes generally present with inherent health concerns and, in some instances, an increased risk of tumor predisposition that necessitate prompt diagnosis and appropriate referral. In this review, we introduce some of the more common overgrowth syndromes, along with their molecular mechanisms, diagnostics, and medical complications for improved recognition and management of patients affected with these disorders.
PubMed: 33194904
DOI: 10.3389/fped.2020.574857 -
Cells Jun 2022In the 30 years since the first report of parental imprinting in insulin-like growth factor 2 () knockout mouse models, we have learnt much about the structure of this... (Review)
Review
In the 30 years since the first report of parental imprinting in insulin-like growth factor 2 () knockout mouse models, we have learnt much about the structure of this protein, its role and regulation. Indeed, many animal and human studies involving innovative techniques have shed light on the complex regulation of expression. The physiological roles of IGF-II have also been documented, revealing pleiotropic tissue-specific and developmental-stage-dependent action. Furthermore, in recent years, animal studies have highlighted important interspecies differences in IGF-II function, gene expression and regulation. The identification of human disorders due to impaired gene expression has also helped to elucidate the major role of IGF-II in growth and in tumor proliferation. The Silver-Russell and Beckwith-Wiedemann syndromes are the most representative imprinted disorders, as they constitute both phenotypic and molecular mirrors of -linked abnormalities. The characterization of patients with either epigenetic or genetic defects altering expression has confirmed the central role of IGF-II in human growth regulation, particularly before birth, and its effects on broader body functions, such as metabolism or tumor susceptibility. Given the long-term health impact of these rare disorders, it is important to understand the consequences of defects in these patients.
Topics: Animals; Beckwith-Wiedemann Syndrome; Epigenomics; Genomic Imprinting; Humans; Insulin-Like Growth Factor II; Mice; Silver-Russell Syndrome
PubMed: 35741015
DOI: 10.3390/cells11121886 -
The Pan African Medical Journal 2023
Topics: Humans; Beckwith-Wiedemann Syndrome
PubMed: 37426460
DOI: 10.11604/pamj.2023.45.17.38741 -
Cancers Nov 2022Placental mesenchymal dysplasia (PMD) is characterized by placentomegaly, aneurysmally dilated chorionic plate vessels, thrombosis of the dilated vessels, and large... (Review)
Review
Placental mesenchymal dysplasia (PMD) is characterized by placentomegaly, aneurysmally dilated chorionic plate vessels, thrombosis of the dilated vessels, and large grapelike vesicles, and is often mistaken for partial or complete hydatidiform mole with a coexisting normal fetus. Androgenetic/biparental mosaicism (ABM) has been found in many PMD cases. Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder with complex and diverse phenotypes and an increased risk of developing embryonal tumors. There are five major causative alterations: loss of methylation of imprinting control region 2 (:TSS-DMR) (ICR2-LOM), gain of methylation at ICR1 (/:IG-DMR) (ICR1-GOM), paternal uniparental disomy of 11 (pUPD11), loss-of-function variants of the gene, and paternal duplication of 11p15. Additional minor alterations include genetic variants within ICR1, paternal uniparental diploidy/biparental diploidy mosaicism (PUDM, also called ABM), and genetic variants of . ABM (PUDM) is found in both conditions, and approximately 20% of fetuses from PMD cases are BWS and vice versa, suggesting a molecular link. PMD and BWS share some molecular characteristics in some cases, but not in others. These findings raise questions concerning the timing of the occurrence of the molecularly abnormal cells during the postfertilization period and the effects of these abnormalities on cell fates after implantation.
PubMed: 36428656
DOI: 10.3390/cancers14225563 -
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