Dampness and moulds in relation to respiratory and allergic symptoms in children : results from phase two of the International Study of Asthma and Allergies in Childhood, (ISAAC Phase Two)

Many studies report that damp housing conditions are associated with respiratory symptoms. Less is known about mechanisms and possible effect modifiers. Studies of dampness in relation to allergic sensitization and eczema are scarce. Objective We study the influence of damp housing conditions world-wide on symptoms and objective outcomes. Cross-sectional studies of 8–12-year-old children in 20 countries used standardized methodology from Phase Two of the International Study of Asthma and Allergies in Childhood (ISAAC). Symptoms of asthma, rhinitis and eczema, plus residential exposure to dampness and moulds, were ascertained by parental questionnaires (n = 46 051). Skin examination, skin prick tests (n = 26 967) and hypertonic saline bronchial challenge (n = 5713) were performed. In subsamples stratified by wheeze (n = 1175), dust was sampled and analysed for house dust mite (HDM) allergens and endotoxin. Current exposure to dampness was more common for wheezy children (pooled odds ratio 1.58, 95% CI 1.40–1.79) and was associated with greater symptom severity among wheezers, irrespective of atopy. A significant (P < 0.01) adverse effect of dampness was also seen for cough and phlegm, rhinitis and reported eczema, but not for examined eczema, nor bronchial hyperresponsiveness. HDM sensitization was more common in damp homes (OR 1.16, 1.03–1.32). HDM-allergen levels were higher in damp homes and were positively associated with HDM-sensitization, but not wheeze. A consistent association of dampness with respiratory and other symptoms was found in both affluent and non-affluent countries, among both atopic and non-atopic children. HDM exposure and sensitization may contribute, but the link seems to be related principally to non-atopic mechanisms.peer-reviewe

47 patients with FLNA associated periventricular nodular heterotopia

Background: Heterozygous loss of function mutations within the Filamin A gene in Xq28 are the most frequent cause of bilateral neuronal periventricular nodular heterotopia (PVNH). Most affected females are reported to initially present with difficult to treat seizures at variable age of onset. Psychomotor development and cognition may be normal or mildly to moderately impaired. Distinct associated extracerebral findings have been observed and may help to establish the diagnosis including patent ductus arteriosus Botalli, progressive dystrophic cardiac valve disease and aortic dissection, chronic obstructive lung disease or chronic constipation. Genotype-phenotype correlations could not yet be established. Methods: Sanger sequencing and MLPA was performed for a large cohort of 47 patients with Filamin A associated PVNH (age range 1 to 65 years). For 34 patients more detailed clinical information was available from a structured questionnaire and medical charts on family history, development, epileptologic findings, neurological examination, cognition and associated clinical findings. Available detailed cerebral MR imaging was assessed for 20 patients. Results: Thirty-nine different FLNA mutations were observed, they are mainly truncating (37/39) and distributed throughout the entire coding region. No obvious correlation between the number and extend of PVNH and the severity of the individual clinical manifestation was observed. 10 of the mutation carriers so far are without seizures at a median age of 19.7 years. 22 of 24 patients with available educational data were able to attend regular school and obtain professional education according to age. Conclusions: We report the clinical and mutation spectrum as well as MR imaging for a large cohort of 47 patients with Filamin A associated PVNH including two adult males. Our data are reassuring in regard to psychomotor and cognitive development, which is within normal range for the majority of patients. However, a concerning median diagnostic latency of 17 to 20 years was noted between seizure onset and the genetic diagnosis, intensely delaying appropriate medical surveillance for potentially life threatening cardiovascular complications as well as genetic risk assessment and counseling prior to family planning for this X-linked dominant inherited disorder with high perinatal lethality in hemizygous males

Consensus recommendations of the german consortium for hereditary breast and ovarian cancer

BACKGROUND: The German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) has established a multigene panel (TruRisk®) for the analysis of risk genes for familial breast and ovarian cancer. SUMMARY: An interdisciplinary team of experts from the GC-HBOC has evaluated the available data on risk modification in the presence of pathogenic mutations in these genes based on a structured literature search and through a formal consensus process. KEY MESSAGES: The goal of this work is to better assess individual disease risk and, on this basis, to derive clinical recommendations for patient counseling and care at the centers of the GC-HBOC from the initial consultation prior to genetic testing to the use of individual risk-adapted preventive/therapeutic measures

Current recommendations for surveillance, risk reduction and therapy in Lynch syndrome patients

Introduction Lynch syndrome (LS) is the most common hereditary colorectal cancer syndrome and accounts for similar to 3 % of all CRCs. This autosomal dominant disorder is caused by germline mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2, and EPCAM). One in 300 individuals of the general population are considered to be mutation carriers (300 000 individuals/Germany). Mutation carriers are at a high CRC risk of 15-46 % till the age of 75 years. LS also includes a variety of extracolonic malignancies such as endometrial, small bowel, gastric, urothelial, and other cancers. Methods The German Consortium for Familial Intestinal Cancer consists of 14 university centers in Germany. The aim of the consortium is to develop and evaluate surveillance programs and to further translate the results in clinical care. We have revisited and updated the clinical management guidelines for LS patients in Germany. Results A surveillance colonoscopy should be performed every 12-24 months starting at the age of 25 years. At diagnosis of first colorectal cancer, an oncological resection is advised, an extended resection (colectomy with ileorectal anastomosis) has to be discussed with the patient. The lifetime risk for gastric cancer is 0.2-13 %. Gastric cancers detected during surveillance have a lower tumor stage compared to symptom-driven detection. The lifetime risk for small bowel cancer is 4-8 %. About half of small bowel cancer is located in the duodenum and occurs before the age of 35 years in 10 % of all cases. Accordingly, patients are advised to undergo an esophagogastroduodenoscopy every 12-36 months starting by the age of 25 years. Conclusion LS colonic and extracolonic clinical management, surveillance and therapy are complex and several aspects remain unclear. In the future, surveillance and clinical management need to be more tailored to gene and gender. Future prospective trials are needed

Consensus Recommendations of the German Consortium for Hereditary Breast and Ovarian Cancer

Background: The German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC) has established a multigene panel (TruRisk (R)) for the analysis of risk genes for familial breast and ovarian cancer. Summary: An interdisciplinary team of experts from the GC-HBOC has evaluated the available data on risk modification in the presence of pathogenic mutations in these genes based on a structured literature search and through a formal consensus process. Key Messages: The goal of this work is to better assess individual disease risk and, on this basis, to derive clinical recommendations for patient counseling and care at the centers of the GC-HBOC from the initial consultation prior to genetic testing to the use of individual risk-adapted preventive/therapeutic measures