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1.
Plast Reconstr Surg Glob Open ; 12(3): e5635, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38463705

RESUMO

Beckwith-Wiedemann syndrome (BWS) is a complex congenital overgrowth disorder necessitating a multidisciplinary approach for effective management. A 5-year-old Saudi girl with BWS received comprehensive care involving various specialists, including a plastic surgeon who performed a keyhole technique tongue reduction to address macroglossia. The intervention resulted in significant improvements in speech and quality of life, with no postoperative complications. Intensive speech therapy further enhanced speech development. This case report emphasizes the importance of a multidisciplinary approach and the critical role of the plastic surgeon in managing BWS patients with macroglossia to achieve optimal outcomes.

2.
Indian J Otolaryngol Head Neck Surg ; 76(1): 490-494, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38440588

RESUMO

Introduction: The proper visualisation of the larynx is required for the diagnostic assessment and therapeutic intervention. The most significant challenges for surgeon is to visualise the anterior commissure of the glottis region. The aim of this study is to record the preoperative laryngoscore in patients posted for endolaryngeal surgery and to assess preoperative predictors for intraoperative difficult laryngeal exposure by correlating with preoperative laryngoscore. Design: Prospective, Cross-sectional, Observational study. Setting: Department of Otorhinolaryngology in a tertiary care teaching facility. Subjects: 150 patients were included with an endolaryngeal disease who were planned for surgery with age > 18yrs. Methodology: In 150 subjects preoperative laryngoscore was calculated, which comprised 11 parameters including thyromental distance, mandibular prognathism, macroglossia, micrognathia, trismus, inter incisor gap, degree of neck flexion-extension, history of prior open-neck surgery or radiotherapy, upper jaw dental status, modified Mallampati score and body mass index in order to produce a total score out of a possible maximum score of 17. According to the anterior commissure visualisation all patients were categorised into five classes, ranging from class 0 to class IV during surgery. The laryngoscore parameters were assessed and compared statistically with five classes of intraoperative anterior commissure visualisation. Result: Out of 150 patients 70 (46.6%) were having 3-4 laryngoscore, followed by 45 (30%) patients with 5-6 laryngoscore. Total 123 (82%) patient had class 0,1 and 2 intraoperative anterior commissure visualisation while 27 (18%) had class 3 and 4 visualisation. If laryngoscore was either less or equal to 5, 90% of the patients had excellent laryngeal exposure whereas only 10% of the patients had challenging laryngeal exposure. At univariate analysis, thyromental distance, degree of neck flexion/extension, and modified Mallampati classification were found statistically significant for difficulty of anterior commissure visualisation independently. Conclusion: A sound, easy and valid preoperative laryngoscore may be significantly helpful in identifying intraoperative difficult laryngeal exposure. This may prevent inadequacy of surgery, abandon of surgery, intra operative complication, and medico-legal cases for laryngologist.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38443190

RESUMO

The aim of this study was to evaluate the postoperative course and long-term functional and aesthetic outcomes in patients with Beckwith-Wiedemann syndrome (BWS) following surgical reduction of macroglossia, using multiple questionnaires. Patients with BWS who underwent keyhole reduction for macroglossia were included in this study. The postoperative course for each patient was recorded, and multiple questionnaires were administered to evaluate aesthetic concerns, oral incompetence or feeding difficulties, sleep-disordered breathing symptoms, and speech. Nine patients underwent ten reduction glossoplasty surgeries. The mean age at surgery was 22 months. The postoperative course for each case was uneventful, except for one patient who had wound dehiscence. The questionnaires revealed significant improvements in tongue appearance, feeding, drooling, facial appearance, and psychosocial outcomes. There was also a significant reduction in sleep-disordered breathing symptoms after surgery. Keyhole reduction glossoplasty is a safe and effective procedure for the treatment of macroglossia in BWS patients, with excellent functional and aesthetic outcomes and a low complication rate.

4.
Clin Case Rep ; 12(3): e8640, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38444926

RESUMO

We are reporting a case of hypothyroidism presenting as fissured tongue, demonstrating significant resolution of fissure tongue upon thyroid hormone replacement therapy.

5.
Plast Reconstr Surg ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38507550

RESUMO

INTRODUCTION: Most patients with Beckwith-Wiedemann syndrome (BWS) have macroglossia with some requiring tongue reduction surgery (TRS). This study reports correlations between levels of affected cells (mosaicism) and BWS clinical score in patients evaluated for TRS. We also show correlations of clinical score and mosaicism with obstructive sleep apnea (OSA) severity. METHODS: Blood mosaicism levels and BWS clinical score were recorded in patients with macroglossia referred to plastic surgery for evaluation. Associations among blood mosaicism, BWS clinical score, TRS, and OSA were assessed with appropriate statistics. RESULTS: Of the 225 patients included, BWS blood testing was available in 128 (56.9%). Mosaicism levels were higher in those who underwent TRS compared to those who did not (85.9 85.9 (56.5-95.9)% vs. 29.7 (2.8-73.1)%, p<0.001). BWS clinical score was also higher in those requiring TRS (9.0 (8.0-11.0) versus 7.0 (6.0-9.0), p<0.001). There was a positive correlation between clinical score and obstructive apnea-hypopnea index (r=0.320, p=0.011). Receiver operating characteristic curve analysis showed a clinical score ≥11 had 100% specificity and 36.4% sensitivity for detecting patients requiring TRS. Blood mosaicism ≥80% had 63.6% sensitivity and 83.6% specificity for predicting surgery. A combined criteria of BWS clinical score ≥11 or mosaicism ≥80% had 72.7% sensitivity and 83.6% specificity for predicting TRS. CONCLUSION: Blood mosaicism levels and higher BWS clinical scores appear associated with a greater frequency of having surgery in patients with macroglossia referred for surgical evaluation. Elevations in BWS clinical scoring are associated with increased OSA severity while increased blood mosaicism is not.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38503668

RESUMO

Oral causes of dysphagia in infancy may involve the lips, the tongue, or the palate. Whereas ankyloglossia is commonly diagnosed in infants with dysphagia, assessment of the need for surgical intervention may be less straightforward. Tongue size (macroglossia) may be associated with dysphagia as it may cause limitation of movement of the food or milk bolus by the lips or cheeks. Congenital conditions such as cleft lip and palate, micrognathia, or craniofacial microsomia may also be associated with dysphagia. Diagnosis and treatment of these conditions can be improved with the engagement of lactation and feeding experts as well as multidisciplinary craniofacial teams.

7.
Arch Endocrinol Metab ; 68: e220395, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38427811

RESUMO

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.


Assuntos
Hiperplasia Suprarrenal Congênita , Síndrome de Beckwith-Wiedemann , Masculino , Lactente , Feminino , Humanos , Recém-Nascido , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/genética , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/genética , Metilação de DNA , Triagem Neonatal
8.
J Pak Med Assoc ; 74(2): 394-397, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38419245

RESUMO

Sturge- Weber syndrome (SWS), is a rare neuro-cutaneous angiomatosis which affects male and females alike. The clinical manifestations include angiomas, haemangiomas of the lips, tongue and palatine region. The oral manifestations are usually unilateral and are susceptible to bleed. Patients can also present with macroglossia and maxillary bone hypertrophy which can lead to malocclusion of the oral cavity. Food accumulation due to occlusion can cause growth of bacteria which can intensify infections and can cause gingival hyperplasia. A case of a middle-aged 39 year old female was reported in the Ziauddin Hospital, Karachi on 2nd of February,2022 with the presenting complaints of intermittent fever and drowsiness for 10 days. On examination she had massive tongue enlargement, drooling, malocclusion, difficulty in eating and breathing. She was a known case of Sturgeweber syndrome. Based on the clinical and radiological findings, she was managed along the lines of prelaryngeal soft tissue and submandibular infection.


Assuntos
Hemangioma , Macroglossia , Macroglossia/congênito , Má Oclusão , Síndrome de Sturge-Weber , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto , Síndrome de Sturge-Weber/complicações , Síndrome de Sturge-Weber/diagnóstico , Macroglossia/etiologia , Hipertrofia
9.
J Med Case Rep ; 18(1): 97, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38369506

RESUMO

BACKGROUND: We present two genetic causes of polyhydramnios that were challenging to diagnose due to their rarity and complexity. In view of the severe implications, we wish to highlight these rare genetic conditions when obstetricians consider differential diagnoses of polyhydramnios in the third trimester. CASE PRESENTATION: Patient 1 is a 34-year-old Asian woman who was diagnosed with polyhydramnios at 28 weeks' gestation. First trimester testing, fetal anomaly scan, and intrauterine infection screen were normal. Subsequent antenatal ultrasound scans revealed macroglossia, raising the suspicion for Beckwith-Wiedemann syndrome. Chromosomal microarray analysis revealed a female profile with no pathological copy number variants. The patient underwent amnioreduction twice in the pregnancy. The patient presented in preterm labor at 34 weeks' gestation but elected for an emergency caesarean section. Postnatally, the baby was noted to have a bell-shaped thorax, coat hanger ribs, hypotonia, abdominal distension, and facial dysmorphisms suggestive of Kagami-Ogata syndrome. Patient 2 is a 30-year-old Asian woman who was diagnosed with polyhydramnios at 30 weeks' gestation. She had a high-risk first trimester screen but declined invasive testing; non-invasive prenatal testing was low risk. Ultrasound examination revealed a macrosomic fetus with grade 1 echogenic bowels but no other abnormalities. Intrauterine infection screen was negative, and there was no sonographic evidence of fetal anemia. She had spontaneous rupture of membranes at 37 + 3 weeks but subsequently delivered by caesarean section in view of pathological cardiotocography. The baby was noted to have inspiratory stridor, hypotonia, low-set ears, and bilateral toe polysyndactyly. Further genetic testing revealed a female profile with a pathogenic variant of the GLI3 gene, confirming a diagnosis of Greig cephalopolysyndactyly syndrome. CONCLUSION: These cases illustrate the importance of considering rare genetic causes of polyhydramnios in the differential diagnosis, particularly when fetal anomalies are not apparent at the 20-week structural scan. We would like to raise awareness for these rare conditions, as a high index of suspicion enables appropriate counseling, prenatal testing, and timely referral to pediatricians and geneticists. Early identification and diagnosis allow planning of perinatal care and birth in a tertiary center managed by a multidisciplinary team.


Assuntos
Doenças Fetais , Poli-Hidrâmnios , Adulto , Feminino , Humanos , Gravidez , Cesárea , Hipotonia Muscular , Poli-Hidrâmnios/diagnóstico por imagem , Poli-Hidrâmnios/genética , Terceiro Trimestre da Gravidez , Ultrassonografia Pré-Natal
10.
J Stomatol Oral Maxillofac Surg ; : 101797, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38354777

RESUMO

The Posterior vertical excess (PVE) associates a symmetric ramus and condyle elongation to an Angle Class III malocclusion. This dento-skeletal discrepancy can be isolated or associated to a condyle hyperplasia or a transverse overgrowth of the mandible due to macroglossia. We present the technique and the postoperative results of bilateral condylectomy applied for the surgical correction of PVE. Bilateral condylectomy represents an alternative to the bimaxillary surgery and adds to the therapeutic arsenal for the correction of Angle Class III malocclusion.

13.
BMC Bioinformatics ; 25(1): 66, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347515

RESUMO

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.


Assuntos
Síndrome de Beckwith-Wiedemann , Síndrome de Silver-Russell , Humanos , Impressão Genômica , Metilação de DNA , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/genética , Síndrome de Silver-Russell/diagnóstico , Síndrome de Silver-Russell/genética , Aprendizado de Máquina Supervisionado
15.
J Vet Intern Med ; 38(1): 135-144, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38180235

RESUMO

BACKGROUND: Muscular dystrophies (MDs) are a large, heterogeneous group of degenerative muscle diseases. X-linked dystrophin-deficient MD in cats is the first genetically characterized cat model for a human disease and a few novel forms have been identified. HYPOTHESIS/OBJECTIVES: Muscular dystrophy was suspected in a young male domestic shorthair cat. Clinical, molecular, and genetic techniques could provide a definitive diagnosis. ANIMALS: A 1-year-old male domestic shorthair cat presented for progressive difficulty walking, macroglossia and dysphagia beginning at 6 months of age. The tongue was thickened, protruded with constant ptyalism, and thickening and rigidity of the neck and shoulders were observed. METHODS: A complete neurological examination, baseline laboratory evaluation and biopsies of the trapezius muscle were performed with owner consent. Indirect immunofluorescence staining of muscle cryosections was performed using several monoclonal and polyclonal antibodies against dystrophy-associated proteins. DNA was isolated for genomic analyses by whole genome sequencing and comparison to DNA variants in the 99 Lives Cat Genome Sequencing dataset. RESULTS AND CLINICAL IMPORTANCE: Aspartate aminotransferase (687 IU/L) and creatine kinase (24 830 IU/L) activities were increased and mild hypokalemia (3.7 mmol/L) was present. Biopsy samples from the trapezius muscle confirmed a degenerative and regenerative myopathy and protein alterations identified by immunohistochemistry resulted in a diagnosis of a in dystrophin-deficient form of X-linked MD. A stop gain variant (c.4849C>T; p.Gln1617Ter) dystrophin was identified by genome sequencing. Precision/genomic medicine efforts for the domestic cat and in veterinary medicine support disease variant and animal model discovery and provide opportunities for targeted treatments for companion animals.


Assuntos
Doenças do Gato , Distrofia Muscular de Duchenne , Humanos , Gatos , Masculino , Animais , Distrofina/genética , Distrofina/análise , Distrofina/metabolismo , Medicina de Precisão/veterinária , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/patologia , Sequenciamento Completo do Genoma/veterinária , DNA , Doenças do Gato/diagnóstico , Doenças do Gato/genética
16.
J Clin Sleep Med ; 20(3): 471-473, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37937612

RESUMO

Obstructive sleep apnea (OSA) is common in children with Down syndrome, with reported prevalence rates as high as 69-76%. Multiple factors predispose children with Down syndrome for OSA, including craniofacial hypoplasia (maxillary and mandibular), airway abnormalities, macroglossia, generalized hypotonia, airway hypotonia, adenotonsillar hypertrophy, and obesity. Despite the fact that the pathophysiology for OSA in children with Down syndrome is multifactorial in nature, treatment methods have focused on soft tissue in the upper airway using adenotonsillectomy and/or continuous positive airway pressure therapy. Here we present a case of a patient with Down syndrome whose severe OSA was approached in a multisystem manner, including upper airway soft tissue, orthognathic, maxillofacial, and bariatric surgery, resulting in resolution of the OSA without reliance on a continuous positive airway pressure device. CITATION: Finch CE, Raol N, Roser SM, Leu RM. Multisystem approach for management of OSA in Down syndrome: a case report. J Clin Sleep Med. 2024;20(3):471-473.


Assuntos
Síndrome de Down , Apneia Obstrutiva do Sono , Criança , Humanos , Síndrome de Down/complicações , Hipotonia Muscular , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/terapia , Nariz , Traqueia
17.
Pediatr Hematol Oncol ; 41(1): 30-40, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37599628

RESUMO

Solid tumors or predisposition syndromes are increasingly suspected before birth. However optimal management and outcomes remain unclear. We have performed a ten-year retrospective study of oncologic indications of prenatal diagnosis in public hospitals in Marseille. Data were obtained from prenatal diagnosis center and hospital imaging databases and pediatric oncology department files. Fifty-one cases were identified, 40 with mass: adrenal 17, sacrococcygeal 9, cardiac 7, abdominal 4, ovarian 1, cervical 2; 8 with developmental abnormalities (omphalocele 4, macroglossia 4), 3 WITH familial predisposition syndromes (familial rhabdoid 2, Li-Fraumeni 1). Median detection time was 30 week. Termination of pregnancy was decided for 9 fetuses (4 cardiac lesions and suspected tuberous sclerosis, 2 sacrococcygeal tumors, 1 Beckwith-Wiedemann Syndrome, 2 SMARCB1 mutations. Preterm birth occurred in 8 cases. Eleven newborns (26,1%) required intensive care (8 for mechanical complications). Of of 17 adrenal mass ES, 4 disappeared before birth and 5 before one year. Seventeen newborns underwent surgery: 13 masses (teratoma 7, myelomeningocele 2, cystic nephroma 1, neuroblastoma 2), 4 omphaloceles, one biopsy. Surgery performed after one year for incomplete regression identified 1 neuroblastoma, 2 bronchogenic cysts and 2 nonmalignant masses. Three newborns received chemotherapy. Except one patient with BWS who died of obstructive apnea, all children are alive disease free with a median follow-up of 60 months [9-131 months]. Twelve have sequelae. Various solid tumors and cancer predisposition syndromes can be detected before birth. A multidisciplinary collaboration is strongly recommended for optimal management before and after birth.


Assuntos
Neuroblastoma , Oncologistas , Nascimento Prematuro , Gravidez , Feminino , Criança , Recém-Nascido , Humanos , Estudos Retrospectivos , Ultrassonografia Pré-Natal , Diagnóstico Pré-Natal
18.
Am J Med Genet A ; 194(1): 88-93, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37632712

RESUMO

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.


Assuntos
Síndrome de Beckwith-Wiedemann , Hemangioma , Lactente , Criança , Recém-Nascido , Humanos , Feminino , Síndrome de Beckwith-Wiedemann/complicações , Síndrome de Beckwith-Wiedemann/diagnóstico , Síndrome de Beckwith-Wiedemann/tratamento farmacológico , Dissomia Uniparental , Propranolol/uso terapêutico , Metilação de DNA , Hemangioma/diagnóstico , Hemangioma/tratamento farmacológico , Hemangioma/genética , Fígado , Impressão Genômica
19.
Cancer ; 130(3): 467-475, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37788149

RESUMO

BACKGROUND: Overgrowth syndromes (e.g., Beckwith-Wiedemann) are associated with an increased risk of pediatric cancer, although there are few population-based estimates of risk. There are also limited studies describing associations between other overgrowth features (e.g., hepatosplenomegaly) and pediatric cancer. Therefore, cancer risk among children with these conditions was evaluated with data from a large, diverse population-based registry linkage study. METHODS: This study includes all live births in Texas during the years 1999-2017. Children with overgrowth features and syndromes were identified from the Texas Birth Defects Registry; children with cancer were identified by linkage to the Texas Cancer Registry. Cox regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between each overgrowth syndrome/feature and cancer, which were adjusted for infant sex and maternal age. RESULTS: In the total birth cohort (n = 6,997,422), 21,207 children were identified as having an overgrowth syndrome or feature. Children with Beckwith-Wiedemann syndrome were 42 times more likely to develop pediatric cancer (95% CI, 24.20-71.83), with hepatoblastoma being the most common, followed by Wilms tumor. The presence of any isolated overgrowth feature was associated with increased cancer risk (HR, 4.70; 95% CI, 3.83-5.77); associations were strongest for hepatosplenomegaly (HR, 23.04; 95% CI, 13.37-39.69) and macroglossia (HR, 11.18; 95% CI, 6.35-19.70). CONCLUSIONS: This population-based assessment confirmed prior findings that children with either overgrowth syndromes or features were significantly more likely to develop cancer. Overall, this study supports recommendations for cancer surveillance in children with these conditions and may also inform future research into cancer etiology.


Assuntos
Síndrome de Beckwith-Wiedemann , Neoplasias Renais , Neoplasias Hepáticas , Tumor de Wilms , Lactente , Criança , Humanos , Incidência , Síndrome de Beckwith-Wiedemann/complicações , Síndrome de Beckwith-Wiedemann/epidemiologia , Síndrome de Beckwith-Wiedemann/genética , Tumor de Wilms/epidemiologia , Neoplasias Renais/complicações , Neoplasias Hepáticas/complicações
20.
Br J Cancer ; 130(4): 638-650, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38142265

RESUMO

BACKGROUND: Wilms tumor (WT) exhibits structural and epigenetic changes at chromosome 11p15, which also cause Beckwith-Wiedemann Syndrome (BWS). Children diagnosed with BWS have increased risk for WT. The aim of this study is to identify the molecular signaling signatures in BWS driving these tumors. METHODS: We performed whole exome sequencing, methylation array analysis, and gene expression analysis on BWS-WT samples. Our data were compared to publicly available nonBWS data. We categorized WT from BWS and nonBWS patients by assessment of 11p15 methylation status and defined 5 groups- control kidney, BWS-nontumor kidney, BWS-WT, normal-11p15 nonBWS-WT, altered-11p15 nonBWS-WT. RESULTS: BWS-WT samples showed single nucleotide variants in BCORL1, ASXL1, ATM and AXL but absence of recurrent gene mutations associated with sporadic WT. We defined a narrow methylation range stratifying nonBWS-WT samples. BWS-WT and altered-11p15 nonBWS-WT showed enrichment of common and unique molecular signatures based on global differential methylation and gene expression analysis. CTNNB1 overexpression and broad range of interactions were seen in the BWS-WT interactome study. CONCLUSION: While WT predisposition in BWS is well-established, as are 11p15 alterations in nonBWS-WT, this study focused on stratifying tumor genomics by 11p15 status. Further investigation of our findings may identify novel therapeutic targets in WT oncogenesis.


Assuntos
Síndrome de Beckwith-Wiedemann , Neoplasias Renais , Tumor de Wilms , Criança , Humanos , Síndrome de Beckwith-Wiedemann/genética , Metilação de DNA , Tumor de Wilms/genética , Genótipo , Neoplasias Renais/genética
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