Aldona Siwińska

Frequency of 22q11.2 microdeletion in children with congenital heart defects in western poland

BackgroundThe 22q11.2 microdeletion syndrome (22q11.2 deletion syndrome -22q11.2DS) refers to congenital abnormalities, including primarily heart defects and facial dysmorphy, thymic hypoplasia, cleft palate and hypocalcaemia. Microdeletion within chromosomal region 22q11.2 constitutes the molecular basis of this syndrome. The 22q11.2 microdeletion syndrome occurs in 1/4000 births. The aim of this study was to determine the frequency of 22q11.2 microdeletion in 87 children suffering from a congenital heart defect (conotruncal or non-conotruncal) coexisting with at least one additional 22q11.2DS feature and to carry out 22q11.2 microdeletion testing of the deleted childrens parents. We also attempted to identify the most frequent heart defects in both groups and phenotypic traits of patients with microdeletion to determine selection criteria for at risk patients.MethodsThe analysis of microdeletions was conducted using fluorescence in situ hybridization (FISH) on metaphase chromosomes and interphase nuclei isolated from venous peripheral blood cultures. A molecular probe (Tuple) specific to the HIRA (TUPLE1, DGCR1) region at 22q11 was used for the hybridisation.ResultsMicrodeletions of 22q11.2 region were detected in 13 children with a congenital heart defect (14.94% of the examined group). Microdeletion of 22q11.2 occurred in 20% and 11.54% of the conotruncal and non-conotruncal groups respectively. Tetralogy of Fallot was the most frequent heart defect in the first group of children with 22q11.2 microdeletion, while ventricular septal defect and atrial septal defect/ventricular septal defect were most frequent in the second group. The microdeletion was also detected in one of the parents of the deleted child (6.25%) without congenital heart defect, but with slight dysmorphism. In the remaining children, 22q11.2 microdeletion originated de novo.ConclusionsPatients with 22q11.2DS exhibit wide spectrum of phenotypic characteristics, ranging from discreet to quite strong. The deletion was inherited by one child. Our study suggests that screening for 22q11.2 microdeletion should be performed in children with conotruncal and non-conotruncal heart defects and with at least one typical feature of 22q11.2DS as well as in the deleted childrens parents.

Who is at higher risk of hypertension? Socioeconomic status differences in blood pressure among Polish adolescents: a population-based ADOPOLNOR study

AbstractIn Poland, there is no data on parental socioeconomic status (SES) as a potent risk factor in adolescent elevated blood pressure, although social differences in somatic growth and maturation of children and adolescents have been recorded since the 1980s. This study aimed to evaluate the association between parental SES and blood pressure levels of their adolescent offspring. A cross-sectional survey was carried out between 2009 and 2010 on a sample of 4941 students (2451 boys and 2490 girls) aged 10–18, participants in the ADOPOLNOR study. The depended outcome variable was the level of blood pressure (optimal, pre- and hypertension) and explanatory variables included place of residence and indicators of parental SES: family size, parental educational attainments and occupation status, income adequacy and family wealth. The final selected model of the multiple multinomial logistic regression analysis (MLRA) with backward elimination procedure revealed the multifactorial dependency of blood pressure levels on maternal educational attainment, paternal occupation and income adequacy interrelated to urbanization category of the place of residence after controlling for family history of hypertension, an adolescent’s sex, age and weight status. Consistent rural-to-urban and socioeconomic gradients were found in prevalence of elevated blood pressure, which increased with continuous lines from large cities through small- to medium-sized cities to villages and from high-SES to low-SES familial environments. The adjusted likelihood of developing systolic and diastolic hypertension decreased with each step increase in maternal educational attainment and increased urbanization category. The likelihood of developing prehypertension decreased with increased urbanization category, maternal education, paternal employment status and income adequacy. Weight status appeared to be the strongest confounder of adolescent blood pressure level and, at the same time, a mediator between their blood pressure and parental SES. Conclusion: The findings of the present study confirmed socioeconomic disparities in blood pressure levels among adolescents. This calls for regularly performed blood pressure assessment and monitoring in the adolescent population. It is recommended to focus on obesity prevention and socioeconomic health inequalities by further trying to improve living and working conditions in adverse rural environments.What is known:• Socioeconomic gradient exists in adolescent blood pressure levels.• Adolescents from lower SES families are at greater risk of hypertension.What is new:• Urbanization levels of residence area affect adolescent blood pressure by parental socioeconomic status.• Socioeconomic inequalities in adolescent hypertension may be modulated through effects of body weight.

Ezrin—a useful factor in the prognosis of nephrotic syndrome in children: an immunohistochemical approach

Background: Minimal change disease (MCD) and diffuse mesangial proliferation (DMP) are the most common pathomorphological forms of nephrotic syndrome glomerulopathies in children. The clinical course of DMP can be characterised by either DMP-sensitivity (DMP-S) or DMP-resistance (DMP-R) to steroids, resulting in an unfavourable course of the glomerulopathy. Although the clinical processes of DMP-S and DMP-R are initially identical, resistance to steroids may be foreseen by the immunohistochemical expression of cytoskeleton-associated proteins in podocytes. Aims: To estimate the immunohistochemical expression of ezrin in children with MCD, DMP and focal segmental glomerulosclerosis (FSGS) and to evaluate its usefulness in predicting resistance to steroids. Materials and methods: Renal biopsy specimens of patients with MCD (n = 15), DMP (n = 16) and FSGS (n = 6) were taken. The control tissue consisted of normal-appearing cortex taken from kidneys resected for localised neoplasms (n = 6). The indirect immunohistochemical protocol for the use of a monoclonal antibody directed against ezrin was used. Results: The immunohistochemical expression of ezrin in cases progressively reduced from MCD to DMP-S to DMP-R to FSGS. Except for DMP-R and FSGS (p>0.05), the difference in ezrin expression in podocytes was significant. Conclusion: Ezrin can be a potent marker of podocyte injury (podocytopathy) and may help in the histological qualification of MCD, DMP and FSGS. The increased permeability of the filtration barrier in steroid-resistant and proteinuric glomerulopathies may be a consequence of subcellular changes in podocyte-associated proteins following decreased expression of ezrin.

Abnormal cytokine synthesis as a consequence of increased intracellular oxidative stress in children treated with dialysis.

Background/Aim: End-stage renal disease (ESRD) induces a clinical state of immunodeficiency with a higher incidence of infections and higher mortality due to infectious complications compared with the normal population. The definite mechanism responsible for the host defense alterations is not well understood. The aim of the study was to investigate intracellularly the relationship between cytokine synthesis and oxidative stress in peripheral blood lymphocytes in children with ESRD. Methods: Twenty-one children (age 11.7 ± 5.8 years) with ESRD treated with hemodialysis (HD; n = 10) and peritoneal dialysis (PD; n = 11) were studied. Nine healthy children of comparable age formed the control group. To determine intracellular oxidative stress we used dihydrorhodamine-123 (DHR), which after oxidation to rhodamine-123 (RHO) emitted a bright fluorescent signal. Intracellular oxidation of DHR in T lymphocytes reflected intracellular oxidative stress. The intracellular synthesis of cytokines (IL-2, IFN-γ, IL-4, IL-6) was also measured. Both parameters were detected at a single-cell level by flow cytometry. Lymphocyte subsets were evaluated using the monoclonal antibodies conjugated with fluorochromes. Results: We found that in T lymphocytes the mean fluorescence intensity (MFI), which reflected intracellular oxidative stress, was increased in ESRD patients compared to the controls (CD3+: 34.77 ± 11.55 vs. 22.55 ± 4.97, p < 0.01; CD3+CD8+: 34.31 ± 12.17 vs. 20.77 ± 4.89, p < 0.01; CD3+CD4+: 36.06 ± 6.98 vs. 24.44 ± 7.68, p < 0.001). HD patients showed slightly higher MFI compared to PD patients in CD3+ cells (39.32 ± 11.70 vs. 30.63 ± 10.20, NS), in CD3+CD8+ cells (37.90 ± 14.32 vs. 31.06 ± 9.34, NS) and in CD3+CD4+ cells (40.10 ± 2.28 vs. 29.33 ± 7.06, p < 0.001). The intracellular synthesis of IL-2 was higher in ESRD patients compared to the controls, both in CD3+ cells (31.34 ± 9.80 vs. 20.49 ± 15.26%, p < 0.05) and in CD3+CD4+ cells (36.10 ± 8.69 vs. 24.03 ± 16.95%, p < 0.05). The intracellular synthesis of IFN-γ, IL-4 and IL-6 was significantly lower in the ESRD group compared to the controls. Interestingly, in patients treated with HD, negative correlations between the degree of intracellular oxidative stress and intracellular cytokine synthesis in CD3+ lymphocytes were found. Conclusion: Our results show that patients with ESRD, especially those treated with HD, present increased oxidative stress in T lymphocytes, which may lead to decreased cytokine synthesis and abnormal immune response.

Mutation of theMYH7 gene in a child with hypertrophic cardiomyopathy and Wolff-Parkinson-White syndrome

Familial hypertrophic cardiomyopathy (HCM) displays autosomal dominant inheritance with incomplete penetration of defective genes. Data concerning the familial occurrence of ventricular preexcitation, i.e. Wolff-Parkinson-White (WPW) syndrome, also indicate autosomal dominant inheritance. In the literature, only a gene mutation on chromosome 7q3 has been described in familial HCM coexisting with WPW syndrome to date. The present paper describes the case of a 7-year-old boy with HCM and coexisting WPW syndrome. On his chromosome 14, molecular diagnostics revealed a C 9123 mutation (arginine changed into cysteine in position 453) in exon 14 in a copy of the gene for beta-myosin heavy chain (MYH7). It is the first known case of mutation of theMYH7 gene in a child with both HCM and WPW. Since no linkage betweenMYH7 mutation and HCM with WPW syndrome has been reported to date, we cannot conclude whether the observed mutation is a common cause for both diseases, or this patient presents an incidental co-occurrence of HCM (caused byMYH7 mutation) and WPW syndrome.

A prospective study to determine the significance of ventricular late potentials in children with mitral valvar prolapse

We aimed prospectively to determine the incidence of ventricular arrhythmias and ventricular late potentials in children with mitral valvar prolapse, and to assess whether signal-averaged electrocardiography could identify which such children were at high risk of developing ventricular tachycardia. In all, we examined 151 children with mitral valvar prolapse, at an age of 12.2 +/- 3.1 years, and 164 healthy subjects aged 12.3 +/- 3.7 years. All children underwent 24-hour ambulatory Holter monitoring and echocardiography. The children with mitral valvar prolapse were followed prospectively for a mean of 64 months. There was a significantly higher prevalence of ventricular arrhythmias in those with prolapse than in the controls (p < 0.0001). Runs of ventricular tachycardia were observed in 3 children with mitral valvar prolapse compared with one from the control group. Late potentials were more frequently observed in the children with mitral valvar prolapse than in those who were healthy (p < 0.0001), and also in those with prolapse suffering ventricular arrhythmias compared with those without ventricular arrhythmias (p < 0.02). During follow-up, 24 children with prolapsing mitral valves developed non-sustained ventricular tachycardia, giving a frequency of 3.1/100 subject-years. The sensitivity of late potentials was low, at 52%, for the identification of children with mitral valvar prolapse who developed ventricular tachycardia, although the specificity was high at 90%. This gave a positive predictive value of 50%, and a negative predictive value of 91%. We conclude that prolapse of the mitral valve predisposes to the development of ventricular arrhythmias and late potentials in children. An abnormal signal-averaged electrocardiogram is a specific, but not very sensitive, predictor for the development of ventricular tachycardia in such children.

Evaluation of cardiac muscle microvessel density in children diagnosed with cyanotic heart defects

Angiogenesis is largely an adaptive response to tissue hypoxia, which occurs in a wide variety of situations. Interestingly, the extent of hypoxia-induces angiogenesis in the cardiac muscle of children diagnosed with congenital cyanotic heart defects is not well established. Thus, the aim of this study was to 1) estimate the cardiac muscle microvessel density (MVD) in children diagnosed with cyanotic (study group) and non-cyanotic (control group) heart defects and to 2) evaluate the prognostic significance of MVD value in the development of ventricular dysfunction in the postoperative period. The study group included 42 children diagnosed with cyanotic heart defects. The control group comprised 33 patients with a diagnosis of non-cyanotic heart failure. The collected tissue included cardiac muscle sections from the right atrium and interventricular or interatrial wall during surgical correction of the defect. Immunocytochemistry with monoclonal mouse anti-human antibodies against CD31, CD34 and CD105 was employed to estimate the MVD value. The mean cardiac muscle MVD, defined by CD34 expression, was 596.7 ± 32.6 microvessels per 1 mm² in the study group, which was notsignificantly different from the mean MVD in the control group (461.2 ± 30.5). Interestingly, in non-cyanotic heart defects, an inner area of subendocardial meshwork was estimated to have 75.3 ± 7.0 microvessels per 1 mm², compared to 92.8 ± 10.9 microvessels per 1 mm² (p = 0.0082) in patients with cyanotic heart defects. No significant correlations between MVD value and ventricular dysfunction were found. Cyanotic heart defects resulting in chronic hypoxia might provoke angiogenesis in the subendocardial meshwork of the heart wall. The process seems to be independent of the type of cyanotic heart disease and most likely takes place during antenatal development. A ventricular dysfunction observed in some cases of cyanotic heart defects could not be predicted by the estimation of MVD.

Environmental variation in the prevalence of hypertension in children and adolescents – is blood pressure higher in children and adolescents living in rural areas?

INTRODUCTION Despite considerable progress in diagnostic methods and treatment options, cardiovascular diseases constitute a serious health issue in Poland, and hypertension is considered one of the main risk factors in the incidence of the diseases. OBJECTIVES The aim of this study is to assess the values of arterial blood pressure among adolescents in the context of urban and rural environments. MATERIALS AND METHOD The study was carried out on a representative, randomly selected group of youths aged 10-18 years, participating in the ADOPOLNOR project. Prior to blood pressure measurement, each pupil was assessed according to anthropomorphic principles. The BP measurements strictly followed the guidelines of the Fourth Protocol of the American Working Group of High Blood pressure in Children and Adolescents. RESULTS Mean values of systolic blood pressure (SBP) in boys in rural areas were higher in every age group than in the boys in urban areas. Higher values of systolic and diastolic blood pressure were observed also in girls in rural areas. BP values sufficiently high for the diagnosis of hypertension were observed in 12.8% of the rural boy population but only in 6.7% of the boys from the urban environment. The difference is statistically significant. The girls in rural areas (13.3%) had twice the incidence of elevated BP values in comparison with the girls in urban areas (7.2%) and, as in boys, the difference is statistically significant. CONCLUSIONS The high proportion of pupils with elevated arterial blood pressure observed in the rural areas of Wielkopolska calls for regularly performed BP assessment and monitoring in this populatio.

Evaluation of medical and psychological parameters of quality of life in supraventricular tachyarrhythmia children. A comparison with healthy children

Introduction There are only a few available studies evaluating quality of life (QoL) in pediatric patients with cardiac arrhythmia. The aim of the study was to evaluate medical and psychological parameters of the QoL in children with a diagnosed supraventricular tachyarrhythmia (SVT) and to compare the obtained data with a group of healthy children (HC). Material and methods Inclusion criteria: children aged 7–18 with SVT, treated at Poznan University of Medical Sciences, Department of Pediatric Cardiology. The evaluation tools were the WHOQOL-BREF instrument and a questionnaire related to the patients feelings and observations concerning arrhythmia (Pediatric Arrhythmia Related Score – PARS), developed by the authors and adjusted to the group of arrhythmia patients. Results The study included 180 SVT children and 83 HC. On the basis of WHOQOL-BREF the SVT group was found to have lower assessment values of QoL within the physical domain (Phd) (mean ± SD: 65.7 ±15.8 vs. 81.6 ±12.8; p < 0.0001) and psychological domain (Psd) (mean ± SD: 75.8 ±15.2 vs. 81.3 ±14.1; p < 0.005). No significant differences were found within the social relationships domain or the environment domain. On the basis of PARS in the SVT group the patients reported significantly increased symptoms within Phd (mean ± SD: 2.3 ±0.7 vs. 1.6 ± 0.3; p < 0.0001) as well as increased negative feelings within Psd (mean ± SD: 2.3 ±0.7 vs. 2.1 ± 0.6; p < 0.005). Conclusions Medical and psychological parameters of the QoL in SVT children are significantly lower in comparison with HC. A diagnosis of SVT has no influence on the social and environmental areas of QoL. The PARS appears to be a useful tool to supplement the generic questionnaire for QoL evaluation in SVT children.

Percentile distribution of blood pressure readings in relation to body mass index: a populationbased cross-sectional study ADOPOLNOR

Abstract Recent upward trends toward elevated blood pressure and increased weight expressed in terms of body mass index in children and adolescents call for regular monitoring of their physical growth and age-related changes in blood pressure. This requires adequate tools - reference values of a normal blood pressure range. The main objective of this study was to provide sex- and BMI-specific percentile reference values for systolic and diastolic blood pressure based on the adolescent Polish population, participants in the ADOPOLNOR study. A cross-sectional survey was carried out on a representative, randomly selected cohort of 4,941; 2,451 male and 2,490 female students aged 10-18 years, residents in Wielkopolska province and its capital, the city of Poznań. All examinations were performed in school nursery rooms during morning hours according to standard procedures. Body height and weight were measured and BMI was calculated. Blood pressure was measured twice on each occasion on the right arm using a fully calibrated TECH MED TM-Z mercury gauge sphygmomanometer with sets of exchangeable cuffs and a clinical stethoscope. The blood pressure classification was determined using the surveillance method. For each participant, the mean of measurements taken on each of the three occasions was calculated and served as his/her final blood pressure value. Using the LMS method, fitted percentile curves were created for BMI-related systolic and diastolic blood pressure. The findings revealed that age related blood pressure pattern was similar in boys and girls. It showed a steady increase of systolic and diastolic blood pressure with age. There was a positive correlation between the systolic and diastolic blood pressure indicating that when systolic blood pressure increased so diastolic did (r=0.61 at p<0.01). Boys were likely to have relatively higher mean values of systolic and diastolic blood pressure and steeper slope for BMI-related change in blood pressure than girls. Similar pattern was found for age-related changes in BMI. The quotation of 3rd, 5th, 10th, 15th, 25th, 50th, 75th, 85th, 90th, 95th, and 97th at any given BMI between 12 kg/m2 and 35 kg/m2 provided indication of the entire variation in blood pressure of adolescent males and females aged 10-18 years. The sex- and BMI-specific reference values and charts for systolic and diastolic blood pressure may be a useful tool in monitoring blood pressure for early detection of its abnormal level and treatment of children and adolescents with high blood pressure.