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      Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement

      review-article
      1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 13 , 17 , 18 , 19 , 2 , 20 , 21 , 22 , 23 , 24 , 25 , 20 , 21 , 26 , 27 , 2 , 11 , 10 , 28 , 29 , 30 , 31 , 13 , 32 , 4 , 10 , 33 , 21 ,
      Nature Reviews. Genetics
      Nature Publishing Group UK
      Medical genetics, Clinical genetics, Disease genetics, Genetic counselling, Genetic testing, Signs and symptoms

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning.

          Abstract

          Cornelia de Lange syndrome is a genetic disorder affecting multiple organ systems that exhibits great phenotypic heterogeneity. This Consensus Statement summarizes recommendations for the diagnosis and management of patients with Cornelia de Lange syndrome.

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          Cohesins: chromosomal proteins that prevent premature separation of sister chromatids.

          Cohesion between sister chromatids opposes the splitting force exerted by microtubules, and loss of this cohesion is responsible for the subsequent separation of sister chromatids during anaphase. We describe three chromosmal proteins that prevent premature separation of sister chromatids in yeast. Two, Smc1p and Smc3p, are members of the SMC family, which are putative ATPases with coiled-coil domains. A third protein, which we call Scc1p, binds to chromosomes during S phase, dissociates from them at the metaphase-to-anaphase transition, and is degraded by the anaphase promoting complex. Association of Scc1p with chromatin depends on Smc1p. Proteins homologous to Scc1p exist in a variety of eukaryotic organisms including humans. A common cohesion apparatus might be used by all eukaryotic cells during both mitosis and meiosis.
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            Update on AUA guideline on the management of benign prostatic hyperplasia.

            To revise the 2003 version of the American Urological Association's (AUA) Guideline on the management of benign prostatic hyperplasia (BPH). From MEDLINE® searches of English language publications (January 1999 through February 2008) using relevant MeSH terms, articles concerning the management of the index patient, a male ≥45 years of age who is consulting a healthcare provider for lower urinary tract symptoms (LUTS) were identified. Qualitative analysis of the evidence was performed. Selected studies were stratified by design, comparator, follow-up interval, and intensity of intervention, and meta-analyses (quantitative synthesis) of outcomes of randomized controlled trials were planned. Guideline statements were drafted by an appointed expert Panel based on the evidence. The studies varied as to patient selection; randomization; blinding mechanism; run-in periods; patient demographics, comorbidities, prostate characteristics and symptoms; drug doses; other intervention characteristics; comparators; rigor and intervals of follow-up; trial duration and timing; suspected lack of applicability to current US practice; and techniques of outcomes measurement. These variations affected the quality of the evidence reviewed making formal meta-analysis impractical or futile. Instead, the Panel and extractors reviewed the data in a systematic fashion and without statistical rigor. Diagnosis and treatment algorithms were adopted from the 2005 International Consultation of Urologic Diseases. Guideline statements concerning pharmacotherapies, watchful waiting, surgical options and minimally invasive procedures were either updated or newly drafted, peer reviewed and approved by AUA Board of Directors. New pharmacotherapies and technologies have emerged which have impacted treatment algorithms. The management of LUTS/BPH continues to evolve. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
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              Clinical practice guideline (update): adult sinusitis.

              This update of a 2007 guideline from the American Academy of Otolaryngology--Head and Neck Surgery Foundation provides evidence-based recommendations to manage adult rhinosinusitis, defined as symptomatic inflammation of the paranasal sinuses and nasal cavity. Changes from the prior guideline include a consumer added to the update group, evidence from 42 new systematic reviews, enhanced information on patient education and counseling, a new algorithm to clarify action statement relationships, expanded opportunities for watchful waiting (without antibiotic therapy) as initial therapy of acute bacterial rhinosinusitis (ABRS), and 3 new recommendations for managing chronic rhinosinusitis (CRS).
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                Author and article information

                Contributors
                r.c.hennekam@amc.uva.nl
                Journal
                Nat Rev Genet
                Nat. Rev. Genet
                Nature Reviews. Genetics
                Nature Publishing Group UK (London )
                1471-0056
                1471-0064
                11 July 2018
                11 July 2018
                2018
                : 19
                : 10
                : 649-666
                Affiliations
                [1 ]Harvey Institute of Human Genetics, Greater Baltimore Medical Centre, Baltimore, MD USA
                [2 ]ISNI 0000 0004 1936 7486, GRID grid.6572.6, Cerebra Centre for Neurodevelopmental Disorders, School of Psychology, , University of Birmingham, ; Birmingham, UK
                [3 ]Department of Paediatrics, Presidio S. Femro, ASST Lariana, Como, Italy
                [4 ]GRID grid.475435.4, Kennedy Centre, Department of Paediatrics and Adolescent Medicine, , Rigshospitalet, ; Glostrup, Denmark
                [5 ]ISNI 0000 0004 1936 8972, GRID grid.25879.31, Division of Human Genetics, Children’s Hospital of Philadelphia, and Department of Pediatrics, , University of Pennsylvania Perelman School of Medicine, ; Philadelphia, PA USA
                [6 ]ISNI 0000 0004 0624 7987, GRID grid.496757.e, GI Department, , Royal Hospital for Sick Children, ; Edinburgh, Scotland UK
                [7 ]ISNI 0000 0001 2179 9593, GRID grid.24827.3b, Departments of Otolaryngology and Pulmonary Medicine, Cincinnati Children’s Hospital Medical Centre, , University of Cincinnati, ; Cincinnati, OH USA
                [8 ]ISNI 0000 0001 2193 0096, GRID grid.223827.e, Division of Pediatric Neurology, Department of Paediatrics, , University of Utah Medical Centre, ; Salt Lake City, UT USA
                [9 ]ISNI 0000 0001 2166 5843, GRID grid.265008.9, Paediatric Ophthalmology and Ocular Genetics, Wills Eye Hospital, , Thomas Jefferson University, ; Philadelphia, PA USA
                [10 ]ISNI 0000 0004 0407 1981, GRID grid.4830.f, Jonx Department of Youth Mental Health and Autism, , Lentis Psychiatric Institute, ; Groningen, Netherlands
                [11 ]ISNI 0000 0001 2152 8769, GRID grid.11205.37, Unit of Clinical Genetics, Paediatrics, University Clinic Hospital ‘Lozano Blesa’ CIBERER-GCV02 and ISS-Aragón, Department of Pharmacology-Physiology and Paediatrics, School of Medicine, , University of Zaragoza, ; Zaragoza, Spain
                [12 ]ISNI 0000 0001 0531 3426, GRID grid.11451.30, Department of Paediatrics, Haematology and Oncology, Department of General Nursery, , Medical University of Gdansk, ; Gdansk, Poland
                [13 ]ISNI 0000 0004 1757 8749, GRID grid.414818.0, Child and Adolescent Neuropsychiatric Unit, , Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, ; Milan, Italy
                [14 ]GRID grid.500099.5, CdLS Foundation UK and Ireland, ; The Tower, North Stifford, Grays, Essex UK
                [15 ]ISNI 0000 0004 0373 8692, GRID grid.413287.b, Harvey Institute of Human Genetics, , Greater Baltimore Medical Center, ; Baltimore, MD USA
                [16 ]Department of Paediatrics, ASST Papa Giovanni XXIII, Bergamo, Italy
                [17 ]ISNI 0000 0004 0593 9113, GRID grid.412134.1, Department of Genetics, INSERM UMR1163, , Université Paris Descartes-Sorbonne Paris Cité, Hôpital Necker-Enfants Malades, ; Paris, France
                [18 ]ISNI 0000 0004 1936 7988, GRID grid.4305.2, Human Genetics Unit, Medical and Developmental Genetics, , University of Edinburgh Western General Hospital, ; Edinburgh, Scotland UK
                [19 ]ISNI 0000 0001 2171 9311, GRID grid.21107.35, Division of Child and Adolescent Psychiatry, , John Hopkins University School of Medicine, ; Baltimore, MD USA
                [20 ]ISNI 0000 0001 0680 8770, GRID grid.239552.a, Centre for Autism Research, , Children’s Hospital of Philadelphia, ; Philadelphia, PA USA
                [21 ]ISNI 0000000084992262, GRID grid.7177.6, Department of Paediatrics, Academic Medical Centre, , University of Amsterdam, ; Amsterdam, Netherlands
                [22 ]ISNI 0000 0001 0057 2672, GRID grid.4562.5, Section for Functional Genetics, Institute for Human Genetics, , University of Lübeck, ; Lübeck, Germany
                [23 ]CdLS World Federation’s, Hertogenbosch, Netherlands
                [24 ]Wicomico County Board of Education, Salisbury, MD USA
                [25 ]ISNI 0000 0004 1756 8604, GRID grid.415025.7, Clinical Paediatric Genetics Unit, Paediatrics Clinics, MBBM Foundation, , S. Gerardo Hospital, ; Monza, Italy
                [26 ]Danbury Public Schools, Danbury, CT USA
                [27 ]ISNI 0000 0001 2171 9311, GRID grid.21107.35, Kennedy Krieger Institute, , Johns Hopkins School of Medicine, ; Baltimore, MD USA
                [28 ]ISNI 0000 0004 0392 3476, GRID grid.240344.5, Department of Gastroenterology, , Nationwide Children’s, ; Columbus, OH USA
                [29 ]Genética Médica, Hospital del Este, Eva Perón, Tucumán, Argentina
                [30 ]ISNI 0000000084992262, GRID grid.7177.6, Department of Clinical Genetics, Academic Medical Centre, , University of Amsterdam, ; Amsterdam, Netherlands
                [31 ]ISNI 0000 0001 2186 7496, GRID grid.264784.b, Department of Educational Psychology and Leadership, , Texas Tech University, ; Lubbock, TX USA
                [32 ]ISNI 0000 0001 2166 5843, GRID grid.265008.9, The Sidney Kimmel Medical College of Thomas Jefferson University, ; Philadelphia, PA USA
                [33 ]ISNI 0000 0000 9558 4598, GRID grid.4494.d, Rob Giel Research Centre, Department of Psychiatry, , University Medical Centre Groningen, ; Groningen, Netherlands
                Article
                31
                10.1038/s41576-018-0031-0
                7136165
                29995837
                63fbaa91-d4ec-491e-a81c-427a88e75605
                © Macmillan Publishers Ltd., part of Springer Nature 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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                Consensus Statement
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                © Springer Nature Limited 2018

                medical genetics,clinical genetics,disease genetics,genetic counselling,genetic testing,signs and symptoms

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