Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care

Mowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS.MethodsIn a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations.ResultsAll anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations.ConclusionKnowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.GENETICS in MEDICINE advance online publication, 4 January 2018; doi:10.1038/gim.2017.221

Phenotype and genotype of 87 patients with Mowat–Wilson syndrome and recommendations for care

Purpose: Mowat–Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype–phenotype correlations of MWS. Methods: In a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations. Results: All anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluati

Nutritional assessment and serum zinc and copper concentration in leukemic children

CONTEXT: Malnutrition in childhood cancer is commonly a serious problem. Changes in blood zinc and copper have also been found in malignant diseases. OBJECTIVE: To describe the protein-energy nutritional status and serum zinc and copper of children with newly diagnosed leukemia. DESIGN: Cross-sectional study. SETTING: University referral center. PARTICIPANTS: 23 children with newly diagnosed acute lymphocytic leukemia (ALL) or acute non-lymphocytic leukemia (ANLL) between the ages of 1and 10 years. The control subjects were 31 healthy school children of similar age from local schools. MAIN MEASURES: Anthropometric measurements of height/age and weight/height, food intake and serum levels of zinc and copper. RESULTS: Almost the entire group of children were eutrophic. Zinc and copper intake were below the recommended values. Serum zinc levels were significantly lower and serum copper levels were significantly higher in the leukemic group when compared to normal children. CONCLUSION: At the time of diagnosis the children suffering from leukemia were not overtly malnourished but blood analysis showed alterations in concentrations of the trace elements zinc and copper

Chromosomal imbalances detected in primary bone tumors by comparative genomic hybridization and interphase fluorescence in situ hybridization

We applied a combination of comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH), to characterize the genetic aberrations in three osteosarcomas (OS) and one Ewing's sarcoma. CGH identified recurrent chromosomal losses at 10p14-pter and gains at 8q22.3-24.1 in OS. Interphase FISH allowed to confirm 8q gain in two cases. A high amplification level of 11q12-qter was detected in one OS. The Ewing's sarcoma showed gain at 1p32-36.1 as the sole chromosome alteration. These studies demonstrate the value of molecular cytogenetic methods in the characterization of recurrent genomic alterations in bone tumor tissue.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Tumores testiculares e paratesticulares na infância Testicular and paratesticular tumors in infancy and chilhood

Este estudo visa apresentar os dados referentes à idade, manifestação clínica, diagnóstico histopatológico e evolução de pacientes pediátricos portadores de neoplasia testicular e paratesticular tratados no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto. Procedeu-se a análise retrospectiva dos prontuários médicos de pacientes, com idade até 18 anos, portadores de neoplasia testicular primária e/ou paratesticular diagnosticados no período compreendido entre janeiro de 1984 a agosto de 2000. Foram atendidos 17 pacientes com idade entre 3 meses e 17 anos (mediana = 3 anos). O acometimento da gônada direita foi semelhante ao da esquerda (n=8 para cada lado), com 1 paciente apresentando tumor bilateral. A manifestação clínica mais frequente foi a de massa escrotal indolor. Nos tumores testiculares houve predomínio das neoplasia de células germinativas (n = 11), e 2 tumores de células de Leydig. Todos os tumores extratesticulares eram rabdomiossarcomas. Apesar da baixa incidência de neoplasia testicular e paratesticular na infância, esse diagnóstico deve ser considerado nos pacientes com massa escrotal indolor

Neuroimaging findings in Mowat-Wilson syndrome: a study of 54 patients

Mowat-Wilson syndrome (MWS) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency of the ZEB2 gene. To date, no characteristic pattern of brain dysmorphology in MWS has been defined.status: publishe