The Ehlers-Danlos syndromes (EDS) are a clinically and genetically heterogeneous group of heritable connective tissue disorders (HCTDs) characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Over the past two decades, the Villefranche Nosology, which delineated six subtypes, has been widely used as the standard for clinical diagnosis of EDS. For most of these subtypes, mutations had been identified in collagenencoding genes, or in genes encoding collagen-modifying enzymes. Since its publication in 1998, a whole spectrum of novel EDS subtypes has been described, and mutations have been identified in an array of novel genes. The International EDS Consortium proposes a revised EDS classification, which recognizes 13 subtypes. For each of the subtypes, we propose a set of clinical criteria that are suggestive for the diagnosis. However, in view of the vast genetic heterogeneity and phenotypic variability of the EDS subtypes, and the clinical overlap between EDS subtypes, but also with other HCTDs, the definite diagnosis of all EDS subtypes, except for the hypermobile type, relies on molecular confirmation with identification of (a) causative genetic variant(s). We also revised the clinical criteria for hypermobile EDS in order to allow for a better distinction from other joint hypermobility disorders. To satisfy research needs, we also propose a pathogenetic scheme, that regroups EDS subtypes for which the causative proteins function within the same pathway. We hope that the revised International EDS Classification will serve as a new standard for the diagnosis of EDS and will provide a framework for future research purposes.

Classical EDS is a heritable disorder of connective tissue. Patients are affected with joint hypermobility, skin hyperextensibilty, and skin fragility leading to atrophic scarring and significant bruising. These clinical features suggest consideration of the diagnosis which then needs to be confirmed, preferably by genetic testing. The most recent criteria for the diagnosis of EDS were devised in Villefranche in 1997 [Beighton et al. (1998); Am J Med Genet 77:31-37].The aims set out in the Villefranche Criteria were: to enable diagnostic uniformity for clinical and research purposes, to understand the natural history of each subtype of EDS, to inform management and genetic counselling, and to identify potential areas of research. The authors recognized that the criteria would need updating, but viewed the Villefranche nosology as a good starting point. Since 1997, there have been major advances in the molecular understanding of classical EDS. Previous question marks over genetic heterogeneity have been largely surpassed by evidence that abnormalities in type V collagen are the cause. Advances in molecular testing have made it possible to identify the causative mutation in the majority of patients. This has aided the further clarification of this diagnosis. The aim of this literature review is to summarize the current knowledge and highlight areas for future research.

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The objective of this study was to evaluate the effectiveness of an asthma education program on morbidity, knowledge, and compliance with inhaled corticosteroid treatment using a prospective, randomized, controlled, one-year-before/one-year-after protocol. After rigorous optimization of asthma therapy under the care of respirologists, patients were assigned to one of three groups: Group C (control group: no formal education), Group P (education and action plan based on peak-flow monitoring), and Group S (education with action plan based on monitoring of asthma symptoms). A total of 188 subjects with moderate to severe asthma were enrolled and 149 completed the study. Asthma morbidity decreased significantly in all groups (p = 0.001). Mean values one-year-before/one-year-after in Groups C, P, and S were: unscheduled medical visits, 2.4/0.8, 2.3/0.7, and 1.9/ 0.7; hospitalizations, 0.21/0.04, 0.24/0.04, and 0.40/0.09; oral steroid treatments; 1.3/0.5, 1.2/0.7, and 1.3/0.9; absenteeism from work/school, 9.6/5.2, 8.8/2.2, and 6.3/2.9. Between-group differences did not reach statistical significance (p > 0.05). Asthma knowledge increased in both educated groups compared with the control group (p < 0.001) as did short-term compliance with inhaled corticosteroids. These results confirm that treatment optimization coupled with sustained high quality care in motivated patients can lead to a significant decrease in asthma morbidity. In such clinical settings, structured asthma education significantly improved short-term compliance with treatment and knowledge about asthma, although it could not add extra benefit with regard to morbidity. Nevertheless, this study does not refute the potential benefit of educational interventions aimed at improving asthma-related morbidity over a longer time period or in patients with less optimal care or with high-risk factors.

The Ehlers-Danlos syndromes (EDS) are a group of heritable, connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. There is phenotypic and genetic variation among the 13 subtypes. The initial genetic findings on EDS were related to alterations in fibrillar collagen, but the elucidation of the molecular basis of many of the subtypes revealed several genes not involved in collagen biosynthesis or structure. However, the genetic basis of the hypermobile type of EDS (hEDS) is still unknown. hEDS is the most common type of EDS and involves generalized joint hypermobility, musculoskeletal manifestations, and mild skin involvement along with the presence of several comorbid conditions. Variability in the spectrum and severity of symptoms and progression of patient phenotype likely depend on age, gender, lifestyle, and expression domains of the EDS genes during development and postnatal life. In this review, we summarize the current molecular, genetic, epidemiologic, and pathogenetic findings related to EDS with a focus on the hypermobile type.