Waardenburg syndrome: clinical differentiation between types I and II

Here we present the results of a study performed on 59 patients affected by Waardenburg syndrome (WS), 30 with the I variant, 21 having the type II, and 8 of them being isolated cases without telecanthus. These patients belong to 37 families; the main contributions and conclusions are based on the detailed study of 25 of these families, examined using standard procedures. All patients were examined as to the presence of eight cardinal signs important for the diagnosis of the condition; from each patient, from many of his/her normal relatives, and from a control sample of 300 normal individuals stratified by age and sex, 23 different craniofacial measurements were obtained. We also estimated, using our own data as well those collected from the literature, the frequencies of the cardinal signs, based on a total sample of 461 affected individuals with WSI and 121 with WSII. In order to originate discriminant functions to separate individuals affected by one of the two variants, both metric (from craniofacial measurements) as well as categoric data (based on the frequencies of the cardinal signs or symptoms) were used. Discriminant analysis based on the frequency of the eight cardinal signs can improve the separation of WSI patients without telecanthus from those presenting the variant II. We present also a Table with the conditional probabilities favoring the diagnosis of WSI for suspect subjects without telecanthus and any combination of the other seven signs/symptoms. The discriminant function based on the four ocular measurements (inner and outer intercanthal, interpupillary, and inferior lacrymal distances), on the other side, perfectly classifies patients affected by one of the variants of WS, the same taking place when the average values of the W index of all affected individuals per family are used. The discriminant function based solely in the individual W index values of patients correctly classifies 93% of WSII subjects, but only 60% of the patients with the I variant of WS.     

Expression of the human NOV gene in first trimester fetal tissues

NOV, located on human chromosome 8q24.1, was originally cloned following discovery of its avian homolog as a consequence of over-expression in virally induced nephroblastoma. The gene product is a secreted, modular, protein and a member of the CCN gene family. Evidence to date indicates that the expression of the wild type protein is associated with cellular quiescence in normal embryonic fibroblasts yet produces growth stimulatory effects on established murine NIH 3T3 cells. Here we report the expression of NOV in the first trimester of human embryogenesis, between 5 and 10 weeks. In situ hybridisation and immunohistochemistry reveal widespread expression in derivatives of all three germ layers. The most abundant sites of expression are in the motor neurons and floor plate of the spinal cord, adrenal cortex, fusing skeletal, and smooth muscle, the urogenital system and the developing heart. Additionally, expression is seen in the cranial ganglia, differentiating chondrocytes, gonads, and lung. The sites of expression suggest strongly that autocrine or paracrine expression of NOV is associated with the process of cell differentiation.     

An investigation of the disclosure process and support needs of BRCA1 and BRCA2 carriers

Disclosure of the results of a positive genetic mutation to offspring can be challenging. The purpose of this study was to investigate the content and process of disclosure from BRCA1/2 carriers to their offspring. A semi-structured questionnaire focused on the disclosure processes between parent and offspring. Thirty-one/40 mothers with BRCA1/2 mutations completed the cross-sectional survey. Sixteen carriers (51.6%) chose to disclose their results to all of their children, thirteen carriers (41.9%) chose not to disclose their results, and two carriers (6.5%) chose to disclose to some of their children. The age of a child appeared to be the most significant contributing factor in the decision to disclose. The mean age of the offspring who learned of the positive test result was 24.3 years with most carriers advocating the ideal age range for disclosure from 19 to 25 years. There was a discrepancy between actual and potential disclosure topics between those who had disclosed and those who had not disclosed at the time of the survey. Women who disclosed their result tended to do so alone, within a week of learning their own results, equally to male and female offspring and expressed that the relationships between themselves and their children had strengthened since revealing the presence of a genetic mutation in the family. Women who had not disclosed the results of their genetic test to offspring were significantly more interested in receiving additional individual counseling, educational videos, and email newsletters that focus on disclosure of this complex and life altering information compared to those who had already disclosed. Disclosure of BRCA1/2 results is determined primarily by age of offspring, is usually done by women alone, relatively soon after receiving results and appears to enhance the relationships between mothers and offspring. Both disclosed and non-disclosed carriers demonstrated significant interest in a variety of interventions to support the disclosure process.     

What Are the Maternal Factors that Potentially Intervenes in the Nutritional Composition of Human Milk?

Background: To evaluate the potential factors associated with the nutritional composition of human milk of puerperal women. Methods: cross-sectional study, conducted between March 2016 and August 2017, with 107 women, selected in a Tertiary Health Care Tertiary Health Facility of the Unified Health System (SUS) in the Municipality of Rio de Janeiro. Data were collected two months after delivery. The dependent variable of the study was the nutritional composition of human milk. We divided the independent variables into hierarchical levels: distal (age, schooling, parity and pregestational nutritional status), intermediate (number of prenatal visits and gestational weight gain) and proximal (alcohol consumption, smoking, diabetes mellitus and hypertension). For data analysis, we applied the multiple linear regression, centered on the hierarchical model. Only the variables associated with the nutritional composition of breast milk remained in the final model at a 5% level of significance. Results: The nutritional composition of human milk yielded by women with pregestational overweight, smokers and hypertensive had higher amounts of lipids and energy. Conversely, women with gestational weight gain below the recommended had lower amounts of these components. Conclusion: The evaluation of factors associated with the nutritional composition of human milk is extremely important to assist post-partum care practices. In this study, we observed that lipid and energy contents were associated to pregestational nutritional status, gestational weight gain, smoking and hypertension.