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

The isolated gamma probe technique for sentinel node penile carcinoma detection is unreliable

PURPOSE: Penile carcinoma is a common disease in northeast Brazil. This paper shows the results of the use of isolated gamma probe and discusses the incidence of false negative rates. MATERIALS AND METHODS: From July 2000 to September 2003, 27 newly diagnosed penile carcinoma patients (T1, T2, N0) were included in this prospective study. The isolated gamma probe technique uses the sodium phytate technetium as a tracer and inguinal scanning with probe and after identified the lymph node it is removed. Lymphadenectomies were performed for positive inguinal lymph nodes metastasis. RESULTS: There were 27 patients (mean age 59.6). Follow up was 37 months. Patients from country were 72% and illiterate or semi-illiterate were 56.7%. The tumors were mostly located in the glans (81.4%). They were T1, 52 % and T2, 48 %. 81.4% of the patients underwent partial penectomy, and 18.6% underwent postectomy and excision with wide margins. In 48% of the patients, the highest radioactive count rate was located on the left side, while in 41% was located on the right side. Only one patient had a positive pathological lymph node metastasis at the moment of the surgery. Additionally 3 patients became inguinal lymph node positive at the follow up. This date yielded a sensibility rate of 25% and a false-negative rate of 42.8%. CONCLUSION: Isolated gamma probe technique for sentinel node penile carcinoma has a very low sensibility and a high false negative rate. Therefore it is highly advisable the addition of others methods such as lymphoscintigraphy, vital blue, ultrasonography and so on. The isolated gamma probe technique for sentinel node penile carcinoma detection is unreliable

Complications in laparoscopic radial cystectomy. The South American experience with 59 cases

Objective: In this study, we have gathered the second largest series yet published on laparoscopic radical cystectomy in order to evaluate the incidence and cause of intra and postoperative complication, conversion to open surgery, and patient mortality. Materials and Methods: From 1997 to 2005,59 laparoscopic radical cystectomies were performed for the management of bladder cancer at 3 institutions in South America. Twenty nine patients received continent urinary diversion, including 25 orthotopic ileal neobladders and 4 Indiana pouches. Only one case of continent urinary diversion was performed completely intracorporeally. Results: Mean operative time was 337 minutes (150-600). Estimated intraoperative blood loss was 488 ml, (50-1500) and 12 patients (20%) required blood transfusion. All 7 (12%) intraoperative complications were vascular in nature, that is, 1 epigastric vessel injury, 2 injuries to the iliac vessels (1 artery and 1 vein), and 4 bleedings that occurred during the bla

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

Purpose: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.Methods:Through brain magnetic resonance imaging (MRI) analysis, we delineated a neuroimaging phenotype in 54 MWS patients with a proven ZEB2 defect, compared it with the features identified in a thorough review of published cases, and evaluated genotype-phenotype correlations.Results:Ninety-six percent of patients had abnormal MRI results. The most common features were anomalies of corpus callosum (79.6% of cases), hippocampal abnormalities (77.8%), enlargement of cerebral ventricles (68.5%), and white matter abnormalities (reduction of thickness 40.7%, localized signal alterations 22.2%). Other consistent findings were large basal ganglia, cortical, and cerebellar malformations. Most features were underrepresented in the literature. We also found ZEB2 variations leading to synthesis of a defective protein to be favorable for psychomotor development and some epilepsy features but also associated with corpus callosum agenesis.Conclusion:This study delineated the spectrum of brain anomalies in MWS and provided new insights into the role of ZEB2 in neurodevelopment