Elastins from patients with Williams-Beuren syndrome and healthy individuals differ on the molecular level.

Williams-Beuren syndrome (WBS) is a congenital disorder, which involves the heterozygous deletion of the elastin gene and other genes on chromosome 7. Clinical symptoms that are associated with hemizygosity of the essential extracellular matrix protein elastin include premature aging of the skin and supravalvular aortic stenosis. However, only little is known about the molecular basis of structural abnormalities in the connective tissue of WBS patients. Therefore, for the first time this study aimed to systematically characterize and compare the structure and amount of elastin present in skin and aortic tissue from WBS patients and healthy individuals. Elastin fibers were isolated from tissue biopsies, and it was found that skin of WBS patients contains significantly less elastin compared to skin of healthy individuals. Scanning electron microscopy and mass spectrometric measurements combined with bioinformatics data analysis were used to investigate the molecular-level structure of elastin. Scanning electron microscopy revealed clear differences between WBS and healthy elastin. With respect to the molecular-level structure, it was found that the proline hydroxylation degree differed between WBS and healthy elastin, while the tropoelastin isoform appeared to be the same. In terms of cross-linking, no differences in the content of the tetrafunctional cross-links desmosine and isodesmosine were found between WBS and healthy elastin. However, principal component analysis revealed differences between enzymatic digests of elastin from healthy probands and WBS patients, which indicates differing susceptibility toward enzymatic cleavage. Overall, the study contributes to a better understanding of the correlation between genotypic and elastin-related phenotypic features of WBS patients. © 2016 Wiley Periodicals, Inc.

The KIDSCREEN-52 quality of life measure for children and adolescents: psychometric results from a cross-cultural survey in 13 European countries.

OBJECTIVE: This study assesses the reliability and validity of the European KIDSCREEN-52 generic health-related quality of life (HRQoL) questionnaire for children and adolescents. RESEARCH DESIGN: The KIDSCREEN-52, which measures HRQoL in 10 dimensions, was administered to a representative sample of 22,827 children and adolescents (8 to 18 years) in 13 European countries. Psychometric properties were assessed using the Classical Test Theory approach, Rasch analysis, and structural equation modeling (SEM). A priori expected associations between KIDSCREEN scales and sociodemographic and health-related factors were examined. Test-retest reliability was assessed in 10 countries. RESULTS: For the overall sample, Cronbach's alpha values ranged from 0.77 to 0.89. Scaling success (Multitrait Analysis Program) was >97.8% for all dimensions and Rasch analysis item fit (INFITmsq) ranged from 0.80 to 1.27. The intraclass correlation coefficients ranged from 0.56 to 0.77. No sizeable differential item functioning (DIF) was found by age, sex or health status. Four items showed DIF across countries. The specified SEM fitted the data well (root mean square error of approximation: 0.06, comparative fit index: 0.98). Correlation coefficients between Pediatric Quality of Life Inventory, Child Health and Illness Profile-Adolescent Edition, and Youth Quality of Life Instrument scales and KIDSCREEN dimensions assessing similar constructs were moderate for those (r = 0.44 to 0.61). Statistically significant differences between children with and without physical and mental health problems (Children with Special Health Care Needs screener: d = 0.17 to 0.42, Strengths and Difficulties Questionnaire: d = 0.32 to 0.72) were found in all dimensions. All dimensions showed a gradient according to socioeconomic status. CONCLUSIONS: The KIDSCREEN-52 questionnaire has acceptable levels of reliability and validity. Further work is needed to assess longitudinal validity and sensitivity to change.

Mental health of children and adolescents in 12 European countries-results from the European KIDSCREEN study.

Within the European Screening for and Promotion of Health-Related Quality of Life in Children and Adolescents-A European Public Health Perspective (KIDSCREEN) Study, emotional well-being and behaviour was examined in national representative samples of 22 000 children and adolescents aged 8 to 18.The proportion of children and adolescents showing signs of mental health problems (Strengths and Difficulties Questionnaire-SDQ) varied across countries and socio-demographic and socio-economic subgroups. Risk factors examined included adverse family climate, low socio-economic status, poor social support and decreased mental well-being of the parents. When several risk factors occur simultaneously, the prevalence of mental health problems increases markedly. Children and adolescents with mental health problems display distinctly impaired health-related quality of life (KIDSCREEN-10).Cross-cultural differences in the observed patterns of mental health problems were discussed. High-risk groups are cross-culturally characterized by poor social support and mental distress of parents. Strengthening social and familial resources should be a key objective, both in prevention and in interventions.

Socioeconomic determinants of health related quality of life in childhood and adolescence: results from a European study.

STUDY OBJECTIVE: The objective of this study was to investigate the impact of two different socioeconomic status (SES) measures on child and adolescent self reported health related quality of life (HRQoL). The European KIDSCREEN project aims at simultaneous developing, testing, and implementing a generic HRQoL instrument. DESIGN AND SETTING: The pilot version of the questionnaire was applied in school surveys to students from 8 to 18 years of age, as well as to their parents, together with such determinants of health status as two SES indicators, the parental educational status and the number of material goods in the family (FAS, family affluence scale). PARTICIPANTS: Students from seven European countries: 754 children (39.8%; mean: 9.8 years), and 1142 adolescents (60.2 %; mean: 14.1 years), as well as their respective parents. MAIN RESULTS: In children, a higher parental educational status was found to have a significant positive impact on the KIDSCREEN dimensions: physical wellbeing, psychological wellbeing, moods and emotions, bullying and perceived financial resources. Increased risk of low HRQoL was detected for adolescents in connection with their physical wellbeing. Family wealth plays a part for children's physical wellbeing, parent relations and home life, and perceived financial resources. For adolescents, family wealth furthermore predicts HRQoL on all KIDSCREEN dimensions. CONCLUSIONS: There is evidence to suggest that exposure to low parental educational status may result in a decreased HRQoL in childhood, whereas reduced access to material (and thereby social) resources may lead to a lower HRQoL especially in adolescence.

Treatment of central precocious puberty and early puberty with GnRH analog in girls with Williams-Beuren syndrome.

OBJECTIVE: Little has been published on treatment of precocious puberty in girls with Williams-Beuren syndrome (WBS), a condition occurring frequently in this group. We analyzed our own data on growth/age at menarche of now adult female patients with WBS being diagnosed with central precocious puberty or early puberty. Data of patients treated with gonadotropin-releasing hormone (GnRH) analog (n=13) were compared with those not treated (control group, n=11). PATIENTS: Longitudinal data on the somatic development of 24 now adult female patients were analyzed. RESULTS: Medium final height was 157.2±6.5 cm compared to 151.4±5.6 cm in the control group. No significant difference could be found in the discrepancy of genetic target height and final height. Prepubertally girls were normal weight in both groups; in adulthood the majority of patients were overweight/obese. Menarche commenced 11 months after cessation of therapy. CONCLUSION: As already known from other studies, hormonal suppression via GnRH analog was well tolerated.

Measuring subjective health in children and adolescents: results of the European KIDSCREEN/DISABKIDS Project.

OBJECTIVES: Currently there is a lack of information regarding the health-related quality of life (HRQoL) of healthy as well as chronically ill children on a European level. In 2 European projects questionnaires for the assessment of the HRQoL in children and adolescents have been developed: The KIDSCREEN project aims at a co-operative European development of a standardised screening instrument for children's HRQoL for the implementation in representative national and European health surveys. In the DISABKIDS project a chronic-generic questionnaire as well as modules for specific conditions (e.g. asthma) were developed for children with chronic conditions. METHODS: Both projects shared similar steps: 1. Development phase, in which the items were generated and tested, 2. Survey and Field phase, in which the modified questionnaires were tested with healthy and chronically ill children and adolescents in national representative surveys, and 3. Implementation phase in national health surveys or clinical studies. RESULTS: In the sister projects, the KIDSCREEN instrument was tested in 22,830 children and the DISABKIDS instrument in 1605 chronically ill children. The current paper describes the development and pilot-testing as well as psychometric results of the field tests of both studies. CONCLUSION: The KIDSCREEN/DISABKIDS instruments make it possible to assess generic, chronic-generic and disease-specific aspects of quality of life in children and present an innovative approach to intercultural HRQoL assessment in health research.

Parent-proxy and child self-reported health-related quality of life: using qualitative methods to explain the discordance.

BACKGROUND: Although parent-proxy reports of health-related quality of life (HRQOL) are only moderately correlated with child reported HRQOL, it remains unknown why these scores differ. The aim of this study was to use a qualitative methodology to examine why parents and children report different levels of HRQOL. METHOD: The sample consisted of 15 parent-child pairs. A think-aloud technique was used where parents and children were given a generic HRQOL instrument (KIDSCREEN) and instructed to share their thoughts with the interviewer. Qualitative analyses were conducted to assess whether parents and children base their answer on different experiences or reasoning, have different response styles, or interpret the items differently. RESULTS: There was discordance between parents and children, in terms of rating scale and in terms of the reasoning for their answer. Children tended to have different response styles to parents, where for example, children tended to provide extreme scores (highest or lowest score) and base their response on one single example, more than parents. Parents and children interpreted the meaning of the items very similarly. DISCUSSION: This study provides evidence to suggest that discordance among parent-child pairs on KIDSCREEN scores may be as a result of different reasoning and different response styles, rather than interpretation of items. These findings have important implications when parent-proxy reported HRQOL is used to guide clinical/treatment decisions.

The KIDSCREEN-27 quality of life measure for children and adolescents: psychometric results from a cross-cultural survey in 13 European countries.

OBJECTIVE: To assess the construct and criterion validity of the KIDSCREEN-27 health-related quality of life (HRQoL) questionnaire, a shorter version of the KIDSCREEN-52. METHODS: The five-dimensional KIDSCREEN-27 was tested in a sample of 22,827. For criterion validity the correlation with and the percentage explained variance of the scores of the KIDSCREEN-52 instrument were examined. Construct validity was assessed by testing a priori expected associations with other generic HRQoL measures (YQOL-S, PedsQL, CHIP), indicators of physical and mental health, and socioeconomic status. Age and gender differences were investigated. RESULTS: Correlation with corresponding scales of the KIDSCREEN-52 ranged from r = 0.63 to r = 0.96, and r2 ranged from 0.39 to 0.92. Correlations between other HRQoL questionnaires and KIDSCREEN-27 dimensions were moderate to high for those assessing similar constructs (r = 0.36 to 0.63). Statistically significant and sizeable differences between physically and mentally healthy and ill children were found in all KIDSCREEN-27 dimensions together with strong associations with psychosomatic complaints (r = -0.52). Most of the KIDSCREEN-27 dimensions showed a gradient according to socio-economic status, age and gender. CONCLUSIONS: The KIDSCREEN-27 seems to be a valid measure of HRQoL in children and adolescents. Further research is needed to assess longitudinal validity and sensitivity to change.

Use of a children questionnaire of health-related quality of life (KIDSCREEN) as a measure of needs for health care services.

PURPOSE: To check if the expected association is observed between children and adolescents' self-perceived health-related quality of life (HRQL) and the use of health care services. METHODS: The data come from the pilot test of a European measure of HRQL for children and adolescents (KIDSCREEN). Children answered the KIDSCREEN 52-item pilot version. Visits to a health professional in the past four weeks and hospitalisation in the past 12 months were collected from parents. A logistic regression model was adjusted to analyse the relationship between the use of health services and HRQL. RESULTS: A total of 2526 children and their parents were included in the analysis. Factors associated to visits in the past four weeks were poor physical well-being (odds ratio [OR] 1.83; 95% confidence interval [CI] 1.42-2.35), and poor school environment (OR 1.32; 95% CI 1.02-1.71). Low scores on moods and emotions was the associated factor to hospitalization in the past 12 months (OR 2.13; 95% CI 1.29-3.81). CONCLUSIONS: Children and adolescents are a feasible source for their self-assessment of HRQL. They should be taken into account in health care needs studies.

KIDSCREEN-52 quality-of-life measure for children and adolescents.

This study describes the development and reports the first psychometric results of the European KIDSCREEN-52 generic health-related quality-of-life questionnaire for children and adolescents. The KIDSCREEN-52, including ten dimensions, was applied in a European survey involving 12 countries (i.e., Austria, Switzerland, Czech Republic, Germany, Greece, Spain, France, Hungary, The Netherlands, Poland, Sweden and the UK) and 22,110 children and adolescents aged between 8 and 18 years of age. Questionnaire development included a literature search, expert consultation, and focus group discussions with children and adolescents. After definition of dimensions and collection of items, a translation process following international translation guidelines, cognitive interviews and a pilot test were performed. Analysis regarding psychometric properties showed Cronbach-alpha ranged from 0.77 to 0.89. Correlation coefficients between KINDL(R) and KIDSCREEN-52 dimensions were high for those assessing similar constructs (r = 0.51-0.68). All KIDSCREEN-52 dimensions showed a gradient according to socioeconomic status and most dimensions showed a gradient according to psychosomatic health complaints. The first results demonstrate that the KIDSCREEN-52 questionnaire is a promising cross-cultural measure of health-related quality-of-life assessment for children and adolescents in Europe.

Risk of sudden death in the Williams-Beuren syndrome.

Williams-Beuren syndrome (WBS) is a genetic disorder characterized by a distinctive facial gestalt, mental retardation, mild growth deficiency, and cardiovascular disease. The occurrence of sudden death in the WBS is known from several case reports, but information about the risk of sudden death as derived from the data of a large cohort of patients is lacking. We analyzed the data of 293 WBS patients who had been treated for 43 years at the same two institutions. We thus collected 5,190 patient years without loss to follow-up. During this period ten patients died. Five of them died from: reticulosarcoma (1), after accident (1), heart failure (1), following heart surgery (2). Of the remaining five patients, four died suddenly and one died of unknown cause suggestive of sudden cardiac death. Thus, the incidence of sudden death in our WBS cohort amounts to 1/1,000 patient years. This risk of sudden death is comparable to that following surgery for congenital heart disease, and is 25-100-fold higher compared to the age-matched normal population.

Central precocious puberty in girls with Williams syndrome.

We report an estimated prevalence of precocious puberty of 1 in 5 to 6 girls with Williams syndrome (18.3%). Mean menarcheal age of 86 girls with Williams syndrome was 11.5 +/- 1.7 (+/-SD) years. Distribution of menarcheal age was significantly different from that in normal girls (12.9 +/- 1.1 years; n = 759).