Background: In patients with juvenile polyposis syndrome (JPS) the frequency of large genomic deletions in the SMAD4 and BMPR1A genes was unknown. Methods: Mutation and phenotype analysis was used in 80 unrelated patients of whom 65 met the clinical criteria for JPS (typical JPS) and 15 were suspected to have JPS. Results: By direct sequencing of the two genes, point mutations were identified in 30 patients (46% of typical JPS). Using MLPA, large genomic deletions were found in 14% of all patients with typical JPS (six deletions in SMAD4 and three deletions in BMPR1A). Mutation analysis of the PTEN gene in the remaining 41 mutation negative cases uncovered a point mutation in two patients (5%). SMAD4 mutation carriers had a significantly higher frequency of gastric polyposis (73%) than did patients with BMPR1A mutations (8%) (p,0.001); all seven cases of gastric cancer occurred in families with SMAD4 mutations. SMAD4 mutation carriers with gastric polyps were significantly older at gastroscopy than those without (p,0.001). In 22% of the 23 unrelated SMAD4 mutation carriers, hereditary hemorrhagic telangiectasia (HHT) was also diagnosed clinically. The documented histologic findings encompassed a wide distribution of different polyp types, comparable with that described in hereditary mixed polyposis syndromes (HMPS). Conclusions: Screening for large deletions raised the mutation detection rate to 60% in the 65 patients with typical JPS. A strong genotype-phenotype correlation for gastric polyposis, gastric cancer, and HHT was identified, which should have implications for counselling and surveillance. Histopathological results in hamartomatous polyposis syndromes must be critically interpreted.

Background-Cystic fibrosis is the most common inherited disease with a fatal outcome in industrialised nations. With the improvement in life expectancy, supporting patients and their families in adapting to life with this chronic progressive disease has become increasingly important. The aim of the present study was to investigate the relationship between health related quality of life (HRQOL) in this population, severity of disease, and cognitive/behavioural factors such as subjective health perception and ways of coping. Methods-A sample of 89 adolescent and adult patients with cystic fibrosis and 125 parents of younger patients with cystic fibrosis completed questionnaires on health related quality of life and on ways of coping with the illness. Parents were asked to fill out the questionnaires regarding their own quality of life and coping. Multiple regression analyses were performed to examine the relationship between diVerent predictor variables and quality of life. Results-After accounting for the impact of disease severity and hours of treatment per day, the subjective health perception of patients significantly explained variance in their quality of life. Ways of coping were also significantly correlated with HRQOL. In parents the most important factor in explaining variance of HRQOL seems to be the coping style, whereas disease severity of the child and subjective health perception did not show any influence. Conclusions-The findings support the important role of cognitive and behavioural factors in specific subjective health perception and ways of coping in the adaptation to this severe chronic disease, both in patients themselves and in parents. The results call for a careful assessment of issues of coping and professional support for families of patients with cystic fibrosis in the early course of disease. (Thorax 1998;53:727-731)

Background: Pediatric lifestyle interventions have positive short-term effects on obese patients. Studies on long-term effects are still scarce in Europe. We investigated long-term weight patterns and sociodemographic predictors of a weight change in a large Central European (Germany, Austria and Switzerland) overweight pediatric cohort. Methods: The APV (Adiposity Patients Verlaufsbeobachtung) database was retrospectively analyzed; 157 specialized childhood obesity centers contributed standardized data of 29,181 patients [body mass index (BMI) ≥90th percentile; 5-25 years old] presenting between 2000 and 2012. BMI standard deviation scores (BMI-SDS) were analyzed in a 2-year follow-up and grouped according to BMI-SDS changes. Multiple logistic regression analyses were conducted to assess associations between sociodemographic factors and weight patterns. Results: 2-year follow-up data were available in 3,135 patients (54.6% female). Five distinct weight trajectories ‘rapid weight loss' (n = 735, 23.4%), ‘delayed success' (n = 697, 22.2%), ‘cycling weight' (n = 43, 1.4%), ‘initial weight loss' and ‘weight rebound' (n = 383, 12.2%) and ‘no weight loss throughout' (n = 1,277, 40.7%) best characterized long-term BMI-SDS changes. Younger and male patients were more likely to reduce weight and maintain weight loss. Conclusions: Our results suggest that an intervention before the onset of puberty seems promising for long-term weight maintenance in overweight children. Thus, new concepts are needed to improve long-term treatment success in patients with lower success rates.

Objective: Comorbidities of childhood obesity challenge health-care systems in Europe. Further, there is a lack of populationspecific prevalence data and diagnostic strategies available, especially for obesity-related disturbances of liver function. Therefore, the prevalence of elevated liver enzymes and their relationship to biological parameters were studied in a large pediatric obesity cohort. Methods: In 111 specialized pediatric obesity centers in Germany, Austria and Switzerland, 16 390 children and adolescents (age 12.4 ± 2.6 years, 58% boys) were categorized as overweight (body mass index (BMI) 490th percentile) and obese (497th percentile) and studied for related comorbidities, especially nonalcoholic fatty liver disease (NAFLD; as defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) 450 U l À1 ). Data were collected using a standardized software program (APV) for longitudinal multicenter documentation. Pseudonymized data were transmitted for central statistical analysis. Results: In this pediatric cohort, 16% of the study population was overweight, 46% obese and 35% extremely obese (499.5th percentile extreme obesity (Xob)). NAFLD was present in 11% of the study population, but predominantly in boys (boys vs girls; 14.4:7.4%; Po0.001), in Xob (obese vs Xob; 9.5:17.0%; Po0.001) and in older age (o 12 vs X12 years; 8:12%; Po0.001; adjusted for BMI). ALT 450 U l À1 was significantly associated with fasting insulin and BMI-SDS. In multiple logistic regression models, Xob and male gender were strongly associated with NAFLD (odds ratio Xob vs normal weight ¼ 3.2; boys vs girls OR ¼ 2.3). Conclusion: In a large cohort of overweight and obese European children and adolescents, markers of nonalcoholic liver disease, especially ALT, are frequent and predicted by Xob and male gender. The results underline the epidemiological dimension of this obesity-related morbidity even in childhood. Therefore, at least ALT is recommended as a screening parameter in basic care.

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Johanson-Blizzard syndrome (JBS) is a rare, autosomal recessive disorder characterized by exocrine pancreatic insufficiency, typical facial features, dental anomalies, hypothyroidism, sensorineural hearing loss, scalp defects, urogenital and anorectal anomalies, short stature, and cognitive impairment of variable degree. This syndrome is caused by a defect of the E3 ubiquitin ligase UBR1, which is part of the proteolytic N-end rule pathway. Herein, we review previously reported (n = 29) and a total of 31 novel UBR1 mutations in relation to the associated phenotype in patients from 50 unrelated families. Mutation types include nonsense, frameshift, splice site, missense, and small in-frame deletions consistent with the hypothesis that loss of UBR1 protein function is the molecular basis of JBS. There is an association of missense mutations and small in-frame deletions with milder physical abnormalities and a normal intellectual capacity, thus suggesting that at least some of these may represent hypomorphic UBR1 alleles. The review of clinical data of a large number of molecularly confirmed JBS cases allows us to define minimal clinical criteria for the diagnosis of JBS. For all previously reported and novel UBR1 mutations together with their clinical data, a mutation database has been established at LOVD.

Leitlinie der Gesellschaft für pädiatrische Gastroenterologie und Ernährung (GPGE) gemeinsam mit der Deutschen Gesellschaft für Kinder-und Jugendmedizin (DGKJ), dem Berufsverband der Kinder-und Jugendärzte (BVKJ), der Deutschen Gesellschaft für pädiatrische Infektiologie (DGPI), der österreichischen Gesellschaft für Kinder-und Jugendheilkunde (ÖGKJ), der Deutschen Gesellschaft für Gastroenterologie, Verdauungs-und Stoffwechselstörungen (DGVS), dem Arbeitskreis "Krankenhaus & Praxishygiene" der AWMF und der Deutschen Gesellschaft für Pflegewissenschaft e. V. (DGPW)

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