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1.
Fetal Pediatr Pathol ; 43(3): 257-265, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38587479

RESUMEN

BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is an overgrowth disorder that exhibits etiologic genomic imprinting characterized by molecular heterogeneity and phenotypic variability. Associations with localized developmental dysplastic chondromatous lesions and cortical neuronal heterotopias have not previously been described. CASE PRESENTATION: A 33-week gestational age female had an omphalocele and intractable hypoglycemia at birth. The placenta demonstrated placental mesenchymal dysplasia. Detection of hypermethylation of IC1 and hypomethylation of IC2 confirmed Beckwith-Wiedemann syndrome, most likely due to uniparental disomy. Additional findings included right mid-tibial and right 5-8th developmental dysplastic chondromatous lesions, absent corpus callosum and numerous right-sided cortical neuronal heterotopias, right hemihypertrophy, multiple cystic hepatic mesenchymal hamartomas and hepatic infantile hemangiomas, nisidioblastosis and cystic pancreatic lesions. The infant died with multi-organ failure and anasarca at 7 weeks of life. CONCLUSION: Beckwith-Wiedemann syndrome anomalies may include multifocal developmental dysplastic chondromatous lesions and cerebral neuronal heterotopias, lateralized, and corpus callosum aplasia.


Asunto(s)
Síndrome de Beckwith-Wiedemann , Recien Nacido Prematuro , Disomía Uniparental , Humanos , Síndrome de Beckwith-Wiedemann/genética , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/patología , Femenino , Recién Nacido , Disomía Uniparental/genética , Disomía Uniparental/diagnóstico , Autopsia , Embarazo , Resultado Fatal
2.
Arch Endocrinol Metab ; 68: e220395, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38427811

RESUMEN

Beckwith-Wiedemann syndrome (BWS) is a common genetic congenital disease characterized by somatic overgrowth and its broad clinical spectrum includes pre- and post-natal macrosomia, macroglossia, visceromegaly, increased risk of neonatal hypoglycemia, and development of embryonic tumors. BWS occurs due to genetic/epigenetic changes involving growth-regulating genes, located on region 11p15, with an important genotype-phenotype correlation. Congenital adrenal hyperplasia (CAH) comprises a spectrum of autosomal recessive diseases presenting a variety of clinical manifestations due to a deficiency in one of the enzymes involved in cortisol secretion. Early diagnosis based on newborn screening prevents the adrenal crisis and early infant death. However, high 17-hydroxyprogesterone (17-OHP) levels can occur in newborns or premature infants without CAH, in situations of stress due to maternal or neonatal factors. Here, we report new cases of false-positive diagnosis of 21-hydroxylase deficiency during newborn screening - two girls and one boy with BWS. Methylation-specific multiplex ligation-dependent probe amplification revealed a gain of methylation in the H19 differentially methylated region. Notably, all three cases showed a complete normalization of biochemical changes, highlighting the transient nature of these hormonal findings that imitate the classical form of CAH. This report sheds light on a new cause of false-positive 21-hydroxylase deficiency diagnosis during newborn screening: Beckwith-Wiedemann syndrome.


Asunto(s)
Hiperplasia Suprarrenal Congénita , Síndrome de Beckwith-Wiedemann , Masculino , Lactante , Femenino , Humanos , Recién Nacido , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/genética , Hiperplasia Suprarrenal Congénita/diagnóstico , Hiperplasia Suprarrenal Congénita/genética , Metilación de ADN , Tamizaje Neonatal
3.
BMC Bioinformatics ; 25(1): 66, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38347515

RESUMEN

BACKGROUND: DNA methylation is one of the most stable and well-characterized epigenetic alterations in humans. Accordingly, it has already found clinical utility as a molecular biomarker in a variety of disease contexts. Existing methods for clinical diagnosis of methylation-related disorders focus on outlier detection in a small number of CpG sites using standardized cutoffs which differentiate healthy from abnormal methylation levels. The standardized cutoff values used in these methods do not take into account methylation patterns which are known to differ between the sexes and with age. RESULTS: Here we profile genome-wide DNA methylation from blood samples drawn from within a cohort composed of healthy controls of different age and sex alongside patients with Prader-Willi syndrome (PWS), Beckwith-Wiedemann syndrome, Fragile-X syndrome, Angelman syndrome, and Silver-Russell syndrome. We propose a Generalized Additive Model to perform age and sex adjusted outlier analysis of around 700,000 CpG sites throughout the human genome. Utilizing z-scores among the cohort for each site, we deployed an ensemble based machine learning pipeline and achieved a combined prediction accuracy of 0.96 (Binomial 95% Confidence Interval 0.868[Formula: see text]0.995). CONCLUSION: We demonstrate a method for age and sex adjusted outlier detection of differentially methylated loci based on a large cohort of healthy individuals. We present a custom machine learning pipeline utilizing this outlier analysis to classify samples for potential methylation associated congenital disorders. These methods are able to achieve high accuracy when used with machine learning methods to classify abnormal methylation patterns.


Asunto(s)
Síndrome de Beckwith-Wiedemann , Síndrome de Silver-Russell , Humanos , Impresión Genómica , Metilación de ADN , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/genética , Síndrome de Silver-Russell/diagnóstico , Síndrome de Silver-Russell/genética , Aprendizaje Automático Supervisado
4.
Clin Genet ; 105(5): 533-542, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38265109

RESUMEN

Beckwith-Wiedemann syndrome (BWS) is an epigenetic overgrowth syndrome. Despite its distinctive growth pattern, the detailed growth trajectories of children with BWS remain largely unknown. We retrospectively analyzed 413 anthropometric measurements over an average of 4.4 years of follow-up in 51 children with BWS. We constructed sex-specific percentile curves for height, weight, and head circumference using a generalized additive model for location, scale, and shape. Males with BWS exhibited greater height at all ages evaluated, weight before the age of 10, and head circumference before the age of 9 than those of the general population. Females with BWS showed greater height before the age of 7, weight before the age of 4.5, and head circumference before the age of 7 than those of the general population. At the latest follow-up visit at a mean 8.4 years of age, bone age was significantly higher than chronological age. Compared to paternal uniparental disomy (pUPD), males with imprinting center region 2-loss of methylation (IC2-LOM) had higher standard deviation score (SDS) for height and weight, while females with IC2-LOM showed larger SDS for head circumference. These disease-specific growth charts can serve as valuable tools for clinical monitoring of children with BWS.


Asunto(s)
Síndrome de Beckwith-Wiedemann , Masculino , Niño , Femenino , Humanos , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/genética , Metilación de ADN/genética , Impresión Genómica , Estudios Retrospectivos , Gráficos de Crecimiento , Trastornos del Crecimiento , República de Corea/epidemiología
5.
J Med Genet ; 61(6): 590-594, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38228391

RESUMEN

Background Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder caused by (epi)genetic alterations at 11p15. Because approximately 20% of patients test negative via molecular testing of peripheral blood leukocytes, the concept of Beckwith-Wiedemann spectrum (BWSp) was established to encompass a broader cohort with diverse and overlapping phenotypes. The prevalence of other overgrowth syndromes concealed within molecularly negative BWSp remains unexplored. Methods We conducted whole-exome sequencing (WES) on 69 singleton patients exhibiting molecularly negative BWSp. Variants were confirmed by Sanger sequencing or quantitative genomic PCR. We compared BWSp scores and clinical features between groups with classical BWS (cBWS), atypical BWS or isolated lateralised overgrowth (aBWS+ILO) and overgrowth syndromes identified via WES. Results Ten patients, one classified as aBWS and nine as cBWS, showed causative gene variants for Simpson-Golabi-Behmel syndrome (five patients), Sotos syndrome (two), Imagawa-Matsumoto syndrome (one), glycosylphosphatidylinositol biosynthesis defect 11 (one) or 8q duplication/9p deletion (one). BWSp scores did not distinguish between cBWS and other overgrowth syndromes. Birth weight and height in other overgrowth syndromes were significantly larger than in aBWS+ILO and cBWS, with varying intergroup frequencies of clinical features. Conclusion Molecularly negative BWSp encapsulates other syndromes, and considering both WES and clinical features may facilitate accurate diagnosis.


Asunto(s)
Síndrome de Beckwith-Wiedemann , Secuenciación del Exoma , Humanos , Síndrome de Beckwith-Wiedemann/genética , Síndrome de Beckwith-Wiedemann/patología , Síndrome de Beckwith-Wiedemann/diagnóstico , Masculino , Femenino , Lactante , Preescolar , Niño , Fenotipo , Trastornos del Crecimiento/genética , Trastornos del Crecimiento/patología , Variación Genética , Mutación/genética
6.
Am J Med Genet A ; 194(1): 88-93, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37632712

RESUMEN

We describe a 2-month-old female infant with macroglossia, macrosomia, omphalocele, neonatal hypoglycemia, earlobe creases, low nasal bridge, midface retrusion, syndromic facies and multiple cutaneous and hepatic hemangiomas (HH). Genetic evaluation confirmed the diagnosis of Beckwith-Wiedemann Syndrome (BWS) with mosaic uniparental disomy 11 as the underlying genetic mechanism suggested by partial hypermethylation of H19/IGF2:IG-DMR and partial hypomethylation of KCNQ1OT1:TSS-DMR on chromosome 11p15.5. Pediatric endocrinology and cardiology assessments were normal. No malignant liver or renal tumors were detected during the follow-up period. Treatment with propranolol was started for the multiple HH, according to international recommendations. At 3-, 6-, and 9-month follow up, a gradual decrease in the size of the hemangiomas and AFP levels was observed, without side effects. This is the fifth case in the literature combining HH and BWS, and among these, the third case with this specific genetic defect suggesting a possible association between HH and BWS caused by 11 paternal uniparental disomy [upd(11)pat]. The case also highlights that if treatment is warranted, then oral propranolol can be used for the management of infantile HH in BWS patients similarly to non-BWS patients.


Asunto(s)
Síndrome de Beckwith-Wiedemann , Hemangioma , Lactante , Niño , Recién Nacido , Humanos , Femenino , Síndrome de Beckwith-Wiedemann/complicaciones , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/tratamiento farmacológico , Disomía Uniparental , Propranolol/uso terapéutico , Metilación de ADN , Hemangioma/diagnóstico , Hemangioma/tratamiento farmacológico , Hemangioma/genética , Hígado , Impresión Genómica
7.
Nat Commun ; 14(1): 7122, 2023 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-37932266

RESUMEN

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.


Asunto(s)
Síndrome de Beckwith-Wiedemann , Hepatoblastoma , Neoplasias Hepáticas , Humanos , Niño , Preescolar , Hepatoblastoma/genética , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/genética , Síndrome de Beckwith-Wiedemann/patología , Neoplasias Hepáticas/genética , Mosaicismo , Metilación de ADN , Impresión Genómica , Microambiente Tumoral
8.
Int J Mol Sci ; 24(17)2023 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-37686168

RESUMEN

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 CDKN1C 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 CDKN1C gene mutations have not been reported to date in BWS.


Asunto(s)
Síndrome de Beckwith-Wiedemann , Síndrome HELLP , Preeclampsia , Femenino , Embarazo , Lactante , Recién Nacido , Humanos , Síndrome HELLP/diagnóstico , Síndrome HELLP/genética , Preeclampsia/genética , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/genética , Retardo del Crecimiento Fetal/genética , Madres , Variación Genética , Inhibidor p57 de las Quinasas Dependientes de la Ciclina/genética
9.
Ital J Pediatr ; 49(1): 127, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37749604

RESUMEN

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.


Asunto(s)
Síndrome de Beckwith-Wiedemann , Femenino , Niño , Embarazo , Humanos , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/genética , Síndrome de Beckwith-Wiedemann/terapia , Genotipo , Fenotipo , Hermanos , Gemelos
11.
Mol Genet Genomic Med ; 11(12): e2264, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37519217

RESUMEN

BACKGROUND: Beckwith-Wiedemann syndrome and Silver-Russel syndrome are two imprinting disorders caused by opposite molecular alterations in 11p15.5. With the current diagnostic tests, their molecular diagnosis is challenging due to molecular heterogeneity and mosaic occurrence of the most frequent alterations. As the determination of precise (epi)genotype of patients is relevant as the basis for a personalized treatment, different approaches are needed to increase the sensitivity of diagnostic testing of imprinting disorders. METHODS: We established methylation-specific droplet digital PCR approaches (MS-ddPCR) for the two imprinting centers in 11p15.5, and analyzed patients with paternal uniparental disomy of chromosome 11p15.5 (upd(11)pat) and other imprinting defects in the region. The results were compared to those from MS-MLPA (multiplex ligation-dependent probe amplification) and MS-pyrosequencing. RESULTS: MS-ddPCR confirmed the molecular alterations in all patients and the results matched well with MS-MLPA. The results of MS-pyrosequencing varied between different runs, whereas MS-ddPCR results were reproducible. CONCLUSION: We show for the first time that MS-ddPCR is a reliable and easy applicable method for determination of MS-associated changes in imprinting disorders. It is therefore an additional tool for multimethod diagnostics of imprinting disorders suitable to improve the diagnostic yield.


Asunto(s)
Síndrome de Beckwith-Wiedemann , Trastornos de Impronta , Síndrome de Silver-Russell , Humanos , Metilación de ADN , Impresión Genómica , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/genética , Síndrome de Silver-Russell/diagnóstico , Síndrome de Silver-Russell/genética , Reacción en Cadena de la Polimerasa Multiplex
13.
Cytogenet Genome Res ; 163(1-2): 32-35, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37369188

RESUMEN

Optical genome mapping (OGM) appears as a new tool for matching standard cytogenetic methods (karyotype and microarray) into a single assay. The chromosomal region 11p15.5 harbours two differentially methylated regions, the imprinting centre regions 1 and 2 (ICR1, ICR2). Disturbances in both regions alter human growth and are associated with two imprinting disorders, Beckwith-Wiedemann (BWS) and Silver-Russell syndromes. Herein, we present a prenatal case with a triplication in 11p15.5, including the H19/IGF2 imprinted region, detected by microarray and OGM. A 30-year-old pregnant woman of 17 weeks of gestation was referred for prenatal karyotype and microarray study because of increased nuchal translucency, short femur, megabladder, hyperechogenic bowel, and renal ectasia. Microarray, OGM, and MS-MLPA were performed, and a tandem cis-triplication in 11p15.5 and hypermethylation of the ICR1 region, compatible with BWS was detected. OGM, with its power to detect all classes of structural variants, including copy number variants, at a higher resolution than traditional cytogenetic methods can play a significant role in prenatal care and management as a next-generation cytogenomic tool. This study further supports the hypotheses that the amplification/duplication-triplication of the H19/IGF2 region could be related to BWS if it is of paternal origin.


Asunto(s)
Síndrome de Beckwith-Wiedemann , Síndrome de Silver-Russell , Embarazo , Femenino , Humanos , Adulto , Impresión Genómica , Síndrome de Beckwith-Wiedemann/genética , Síndrome de Beckwith-Wiedemann/diagnóstico , Metilación de ADN/genética , Síndrome de Silver-Russell/genética , Mapeo Cromosómico , Factor II del Crecimiento Similar a la Insulina/genética
15.
J Pediatr Hematol Oncol ; 45(4): e525-e529, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36730589

RESUMEN

Beckwith-Wiedemann syndrome (BWS) is an epigenetic overgrowth disorder and cancer predisposition syndrome caused by imprinting defects of chromosome 11p15.5-11p15.4. BWS should be considered in children with atypical presentations of embryonal tumors regardless of clinical phenotype. Risk of malignancy correlates with specific molecular subgroups of BWS making molecular subclassification important for appropriate cancer screening. We report the first case of concurrent embryonal tumors in a phenotypically normal child, leading to the diagnosis of BWS with paternal uniparental disomy and describe the molecular classification of BWS as it relates to malignancy risk, along with approach to management.


Asunto(s)
Síndrome de Beckwith-Wiedemann , Hepatoblastoma , Neoplasias Renales , Neoplasias Hepáticas , Neoplasias de Células Germinales y Embrionarias , Tumor de Wilms , Humanos , Síndrome de Beckwith-Wiedemann/complicaciones , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/genética , Hepatoblastoma/etiología , Hepatoblastoma/genética , Impresión Genómica , Tumor de Wilms/diagnóstico , Tumor de Wilms/genética , Fenotipo , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/genética , Neoplasias Renales/genética , Neoplasias de Células Germinales y Embrionarias/genética , Metilación de ADN
16.
Z Geburtshilfe Neonatol ; 227(3): 227-230, 2023 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-36693412

RESUMEN

Beckwith-Wiedemann syndrome (BWS) is a genetic disease with phenotypic variability and the following signs: macroglossia, asymmetry, lateralised overgrowth, overgrowth of the internal organs, abdominal wall defects, neonatal hypoglycemia and increased risk of embryonic tumours. The prevalence is reported as being between 1 in 10,000 and 1 in 21,000 live births. The disease is caused by molecular changes in gene clusters on the short arm of chromosome 11 region P15.5. We present the case of a female, born preterm at 32 0/7 weeks. A UPD(11)pat-mutation was diagnosed postnatally. The particular feature of her case was an early tongue reduction surgery which was necessary because of drinking and breathing difficulties. Long-lasting hypoglycemia was difficult to treat.


Asunto(s)
Síndrome de Beckwith-Wiedemann , Hipoglucemia , Macroglosia , Recién Nacido , Humanos , Femenino , Síndrome de Beckwith-Wiedemann/complicaciones , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/epidemiología , Macroglosia/diagnóstico , Macroglosia/etiología , Macroglosia/cirugía , Hipoglucemia/diagnóstico , Hipoglucemia/complicaciones
17.
Jt Dis Relat Surg ; 34(1): 3-8, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36700257

RESUMEN

OBJECTIVES: This study aims to increase the awareness of the association between lateralized overgrowth (LO) and abdominal tumor among the pediatric orthopedic community and to evaluate its incidence in our center. PATIENTS AND METHODS: Between January 1997 and December 2021, a total of 166 patients with Wilms tumors and hepatoblastomas were retrospectively analyzed. Data including age, sex, initial clinical signs (hematuria, abdominal mass with or without general discomfort), type of asymmetric regional body overgrowth (isolated or in relation with any syndrome), and tumor stage at diagnosis were recorded. In addition, age at which asymmetric regional body overgrowth was described and age at the time of tumor diagnosis were noted. RESULTS: Of a total of 166 patients, 133 were diagnosed with Wilms tumors (nephroblastomas) and 33 were diagnosed with hepatoblastomas. In 94% of the cases, the initial clinical signs were an abdominal mass and/or hematuria. Overall, five (3%) patients presented with LO. Four patients with Wilms tumor presented it at the initial clinical examinations. In three of these cases (2.3%), we found it isolated and, in the remaining patient (0.75%), it was associated with Beckwith-Wiedemann spectrum. Only one patient affected from hepatoblastoma (3%) presented with an isolated LO at the time of tumor diagnosis. CONCLUSION: Our study results show an incidence of LO in relation to intra-abdominal tumors of 3%. The latest updates recommend genetic testing to identify subgroups with a higher risk for tumor development that are more likely to benefit from tumor protocol surveillance.


Asunto(s)
Neoplasias Abdominales , Síndrome de Beckwith-Wiedemann , Hepatoblastoma , Neoplasias Renales , Neoplasias Hepáticas , Cirujanos Ortopédicos , Tumor de Wilms , Niño , Humanos , Hepatoblastoma/diagnóstico , Hepatoblastoma/epidemiología , Hepatoblastoma/complicaciones , Síndrome de Beckwith-Wiedemann/complicaciones , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/genética , Estudios Retrospectivos , Hematuria/complicaciones , Tumor de Wilms/diagnóstico , Tumor de Wilms/epidemiología , Tumor de Wilms/etiología , Neoplasias Abdominales/epidemiología , Neoplasias Abdominales/complicaciones , Neoplasias Renales/epidemiología , Neoplasias Renales/complicaciones , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/complicaciones
18.
Am J Med Genet A ; 191(2): 348-356, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36322462

RESUMEN

Beckwith-Wiedemann Spectrum (BWSp) is an overgrowth and cancer predisposition disorder characterized by a wide spectrum of phenotypic manifestations including macroglossia, abdominal wall defects, neonatal hypoglycemia, and predisposition to embryonal tumors. In 1981, Best and Hoekstra reported four patients with BWSp in a single family which suggested autosomal dominant inheritance, but standard clinical testing for BWSp was not available during this time. Meticulous phenotyping of this family has occurred over the past 40 years of follow-up with additional family members being identified and samples collected for genetic testing. Genetic testing revealed a pathogenic mutation in CDKN1C, consistent with the most common cause of familial BWSp. CDKN1C mutations account for just 5% of sporadic cases of BWSp. Here, we report the variable presentation of BWSp across the individuals affected by the CDKN1C mutation and other extended family members spanning multiple generations, all examined by the same physician. Additional phenotypes thought to be atypical in patients with BWSp were reported which included cardiac abnormalities. The incidence of tumors was documented in extended family members and included rhabdomyosarcoma, astrocytoma, and thyroid carcinoma, which have previously been reported in patients with BWSp. These observations suggest that in addition to the inheritance of the CDKN1C variant, there are modifying factors in this family driving the phenotypic spectrum observed. Alternative theories are suggested to explain the etiology of clinical variability including diffused mosaicism, anticipation, and the presence of additional variants tracking in the family. This study highlights the necessity of long-term follow-up in patients with BWSp and consideration of individual familial characteristics in the context of phenotype and/or (epi)genotype associations.


Asunto(s)
Astrocitoma , Síndrome de Beckwith-Wiedemann , Humanos , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/genética , Síndrome de Beckwith-Wiedemann/patología , Familia Extendida , Fenotipo , Genotipo , Astrocitoma/genética , Impresión Genómica
19.
Audiol., Commun. res ; 28: e2740, 2023. tab, graf
Artículo en Portugués | LILACS | ID: biblio-1439467

RESUMEN

RESUMO O objetivo deste estudo foi relatar a abordagem interdisciplinar no manejo da macroglossia em um caso de paciente com síndrome de Beckwith-Wiedemann, no período de dez anos. O acompanhamento iniciou pela equipe de Cirurgia Bucomaxilofacial, seguido da Fonoaudiologia, em função de dificuldades alimentares. Após avaliação clínica e instrumental, aos 8 meses de idade, iniciou-se a intervenção fonoaudiológica com foco na disfagia orofaríngea e na terapia miofuncional orofacial. Foi verificado, com 1 ano e 11 meses, ausência de sinais de alteração de deglutição em fase faríngea e melhora na postura de lábios e língua. Aos 3 anos, foram iniciados estímulos para retirada dos hábitos orais e o treino da função mastigatória. O tratamento ortodôntico para correção de mordida aberta anterior e mordida cruzada posterior unilateral iniciou-se aos 6 anos. Aos 7 anos e 5 meses de idade, constatou-se estabilidade do modo respiratório nasal e adequação da postura de repouso de lábios e língua. Aos 9 anos, em função de recidiva das alterações oclusais, optou-se pela redução cirúrgica da língua seguida de terapia miofuncional orofacial, retomada aos 9 anos e 3 meses. O resultado foi a correção da postura da língua na deglutição e a adequação da fala. A associação dos tratamentos, envolvendo Fonoaudiologia, Ortodontia e Cirurgia Bucomaxilofacial foi considerada efetiva no manejo da macroglossia, resultando na adequação e equilíbrio das funções orofaciais.


ABSTRACT This study aims to report the interdisciplinary management of macroglossia in a Beckwith-Wiedemann syndrome patient during ten years. Clinical follow-up started by the Oral and Maxillofacial Surgery team, followed by Speech Therapy due to feeding difficulties. After clinical and instrumental evaluation, at 8 months old, the speech therapy intervention was indicated, focusing on oropharyngeal dysphagia and orofacial myofunctional therapy. At 1 year and 11 months, no signs of swallowing alteration in the pharyngeal phase and improvement in the posture of the lips and tongue were found. At the age of 3, stimulation to remove oral habits and train masticatory function were initiated. Orthodontic treatment to correct anterior open bite and unilateral posterior crossbite started at age 6. At 7 years and 5 months, there was stability in the nasal breathing mode and adequacy of resting posture of lips and tongue. At the age of 9, due to relapse of the occlusal alterations, surgical reduction of the tongue was indicated, followed by orofacial myofunctional therapy, restarted at the age of 9 years and 3 months. The result was the correction of the posture of the tongue during swallowing and speech adequacy. The association of treatments involving Speech Therapy, Orthodontics and Oral and Maxillofacial Surgery was considered effective in the management of the macroglossia. It resulted in the adequacy and equilibrium of orofacial functions.


Asunto(s)
Humanos , Masculino , Niño , Grupo de Atención al Paciente , Síndrome de Beckwith-Wiedemann/diagnóstico , Terapia Miofuncional/métodos , Glosectomía , Macroglosia/terapia , Ortodoncia , Fonoaudiología
20.
Pediatr. aten. prim ; 24(96)oct.- dic. 2022. tab
Artículo en Español | IBECS | ID: ibc-214403

RESUMEN

El síndrome de Beckwith Wiedemann es una enfermedad poco frecuente que tiene una prevalencia de 1 por cada 10 340 personas. Se caracteriza por presentar macrosomía, macroglosia, defectos en la pared abdominal, organomegalia, hipercrecimiento lateralizado y un riesgo aumentado de desarrollo de tumores en los primeros años de vida. En este artículo se presenta un protocolo actualizado para el manejo de esta patología en la consulta de Atención Primaria. Por otra parte, este síndrome nos sirve como ejemplo para ilustrar el importante papel que cumplen las asociaciones de pacientes en prestar apoyo a estas personas y a sus familiares, así como en incrementar la visibilidad de las enfermedades raras e incentivar la investigación (AU)


Beckwith Wiedemann syndrome is a rare disease with a prevalence of 1 in 10,340 persons. It is characterized by macrosomia, macroglossia, abdominal wall defects, organomegaly, lateralized overgrowth and an increased risk of tumor development in the first years of life. This article presents an updated protocol for the management of this pathology in the primary care clinic. On the other hand, this syndrome serves as an example to illustrate the important role that patient associations play in supporting these individuals and their families, as well as in increasing the visibility of rare diseases and encouraging research. (AU)


Asunto(s)
Humanos , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/terapia , Atención Primaria de Salud , Enfermedades Raras , Estudios de Seguimiento
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