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.

By exome sequencing, we found de novo SMARCB1 mutations in two of five individuals with typical Coffin-Siris syndrome (CSS), a rare autosomal dominant anomaly syndrome. As SMARCB1 encodes a subunit of the SWItch/Sucrose NonFermenting (SWI/SNF) complex, we screened 15 other genes encoding subunits of this complex in 23 individuals with CSS. Twenty affected individuals (87%) each had a germline mutation in one of six SWI/SNF subunit genes, including SMARCB1, SMARCA4, SMARCA2, SMARCE1, ARID1A and ARID1B.

The Ehlers–Danlos syndromes comprise a clinically and genetically heterogeneous group of heritable connective tissue disorders, which are characterized by joint hypermobility, skin hyperextensibility, and tissue friability. In the Villefranche Nosology, six subtypes were recognized: The classical, hypermobile, vascular, kyphoscoliotic, arthrochalasis, and dermatosparaxis subtypes of EDS. Except for the hypermobile subtype, defects had been identified in fibrillar collagens or in collagen‐modifying enzymes. Since 1997, a whole spectrum of novel, clinically overlapping, rare EDS‐variants have been delineated and genetic defects have been identified in an array of other extracellular matrix genes. Advances in molecular testing have made it possible to now identify the causative mutation for many patients presenting these phenotypes. The aim of this literature review is to summarize the current knowledge on the rare EDS subtypes and highlight areas for future research. © 2017 Wiley Periodicals, Inc.

Management of neonates with trisomy 18 is controversial, supposedly due to the prognosis and the lack of precise clinical information concerning efficacy of treatment. To delineate the natural history of trisomy 18 managed under intensive treatment, we reviewed detailed clinical data of 24 patients with full trisomy 18 admitted to the neonatal intensive care unit of Nagano Children's Hospital, providing intensive treatment to those with trisomy 18, from 1994 to 2003. Cesarean, resuscitation by intubation, and surgical operations were performed on 16 (67%), 15 (63%), and 10 (42%) of the patients, respectively. Mechanical ventilation was required by 21 (88%), and 6 (29%) of them were extubated. Survival rate at age 1 week, 1 month, and 1 year was 88%, 83%, and 25%, respectively. Median survival time was 152.5 days. Respiration was not stabilized in two patients with left diaphragmatic eventration and hypoplasia accompanied by lung hypoplasia, even with maximal ventilation. The common underlying factors associated with death were congenital heart defects and heart failure (96%), followed by pulmonary hypertension (78%). The common final modes of death were sudden cardiac or cardiopulmonary arrest (26%) and possible progressive pulmonary hypertension-related events (26%). These data of improved survival, through neonatal intensive treatment, are helpful for clinicians to offer the best information on treatment options to families of patients with trisomy 18. ß 2006 Wiley-Liss, Inc.

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