Consensus statement on standards and guidelines for the molecular diagnostics of Alport syndrome: refining the ACMG criteria.
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ABSTRACT:
SUBMITTER: Savige J
PROVIDER: S-EPMC8384871 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAngelman syndrome (AS) is a rare neurogenetic disorder present in approximately 1/12,000 individuals and characterized by developmental delay, cognitive impairment, motor dysfunction, seizures, gastrointestinal concerns, and abnormal electroencephalographic background. AS is caused by absent expression of the paternally imprinted gene UBE3A in the central nervous system. Disparities in the management of AS are a major problem in preparing for precision therapies and occur even in patients with access to experts and recognized clinics. AS patients receive care based on collective provider experience due to limited evidence-based literature. We present a consensus statement and comprehensive literature review that proposes a standard of care practices for the management of AS at a critical time when therapeutics to alter the natural history of the disease are on the horizon.MethodsWe compiled the key recognized clinical features of AS based on consensus from a team of specialists managing patients with AS. Working groups were established to address each focus area with committees comprised of providers who manage >5 individuals. Committees developed management guidelines for their area of expertise. These were compiled into a final document to provide a framework for standardizing management. Evidence from the medical literature was also comprehensively reviewed.ResultsAreas covered by working groups in the consensus document include genetics, developmental medicine, psychology, general health concerns, neurology (including movement disorders), sleep, psychiatry, orthopedics, ophthalmology, communication, early intervention and therapies, and caregiver health. Working groups created frameworks, including flowcharts and tables, to help with quick access for providers. Data from the literature were incorporated to ensure providers had review of experiential versus evidence-based care guidelines.ConclusionStandards of care in the management of AS are keys to ensure optimal care at a critical time when new disease-modifying therapies are emerging. This document is a framework for providers of all familiarity levels.
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Project description:Mitochondrial DNA (mtDNA) variant pathogenicity interpretation has special considerations given unique features of the mtDNA genome, including maternal inheritance, variant heteroplasmy, threshold effect, absence of splicing, and contextual effects of haplogroups. Currently, there are insufficient standardized criteria for mtDNA variant assessment, which leads to inconsistencies in clinical variant pathogenicity reporting. An international working group of mtDNA experts was assembled within the Mitochondrial Disease Sequence Data Resource Consortium and obtained Expert Panel status from ClinGen. This group reviewed the 2015 American College of Medical Genetics and Association of Molecular Pathology standards and guidelines that are widely used for clinical interpretation of DNA sequence variants and provided further specifications for additional and specific guidance related to mtDNA variant classification. These Expert Panel consensus specifications allow for consistent consideration of the unique aspects of the mtDNA genome that directly influence variant assessment, including addressing mtDNA genome composition and structure, haplogroups and phylogeny, maternal inheritance, heteroplasmy, and functional analyses unique to mtDNA, as well as specifications for utilization of mtDNA genomic databases and computational algorithms.
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Project description:ObjectiveTo establish criteria for the diagnosis of progressive multifocal leukoencephalopathy (PML).MethodsWe reviewed available literature to identify various diagnostic criteria employed. Several search strategies employing the terms "progressive multifocal leukoencephalopathy" with or without "JC virus" were performed with PubMed, SCOPUS, and EMBASE search engines. The articles were reviewed by a committee of individuals with expertise in the disorder in order to determine the most useful applicable criteria.ResultsA consensus statement was developed employing clinical, imaging, pathologic, and virologic evidence in support of the diagnosis of PML. Two separate pathways, histopathologic and clinical, for PML diagnosis are proposed. Diagnostic classification includes certain, probable, possible, and not PML.ConclusionDefinitive diagnosis of PML requires neuropathologic demonstration of the typical histopathologic triad (demyelination, bizarre astrocytes, and enlarged oligodendroglial nuclei) coupled with the techniques to show the presence of JC virus. The presence of clinical and imaging manifestations consistent with the diagnosis and not better explained by other disorders coupled with the demonstration of JC virus by PCR in CSF is also considered diagnostic. Algorithms for establishing the diagnosis have been recommended.
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Project description:Genetic testing for pathogenic COL4A3-5 variants is usually undertaken to investigate the cause of persistent hematuria, especially with a family history of hematuria or kidney function impairment. Alport syndrome experts now advocate genetic testing for persistent hematuria, even when a heterozygous pathogenic COL4A3 or COL4A4 is suspected, and cascade testing of their first-degree family members because of their risk of impaired kidney function. The experts recommend too that COL4A3 or COL4A4 heterozygotes do not act as kidney donors. Testing for variants in the COL4A3-COL4A5 genes should also be performed for persistent proteinuria and steroid-resistant nephrotic syndrome due to suspected inherited FSGS and for familial IgA glomerulonephritis and kidney failure of unknown cause.
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Project description:BackgroundReporting guidelines for different study designs are currently available to report studies with accuracy and transparency. There is a need to develop supplementary guideline items that are specific to areas within Pediatric Dentistry. This study aims to develop Reporting stAndards for research in PedIatric Dentistry (RAPID) guidelines using a pre-defined expert consensus-based Delphi process.MethodsThe development of the RAPID guidelines was based on the Guidance for Developers of Health Research Reporting Guidelines. Following a comprehensive search of the literature, the Executive Group identified ten themes in Pediatric Dentistry and compiled a draft checklist of items under each theme. The themes were categorized as: General, Oral Medicine, Pathology and Radiology, Children with Special Health Care Needs, Sedation and Hospital Dentistry, Behavior Guidance, Dental Caries, Preventive and Restorative Dentistry, Pulp Therapy, Traumatology, and Interceptive Orthodontics. A RAPID Delphi Group (RDG) was formed comprising of 69 members from 15 countries across six continents. Items were scored using a 9-point rating Likert scale. Items achieving a score of seven and above, marked by at least 70% of RDG members were accepted into the RAPID checklist items. Weighted mean scores were calculated for each item. Statistical significance was set at p < 0.05 and one-way ANOVA was used to calculate the difference in the weighted mean scores between the themes.ResultsThe final RAPID checklist comprised of 128 items that were finalized and approved by the RDG members in the online consensus meeting. The percentage for high scores (scores 7 to 9) ranged from 69.57 to 100% for individual items. The overall weighted mean score of the final items ranged from 7.51 to 8.28 (out of 9) and the difference was statistically significant between the themes (p < 0.05).ConclusionsThe RAPID statement provides guidance to researchers, authors, reviewers and editors, to ensure that all elements relevant to particular studies are adequately reported.
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Project description:PurposeThe number of cancer survivors worldwide is growing, with over 15.5 million cancer survivors in the United States alone-a figure expected to double in the coming decades. Cancer survivors face unique health challenges as a result of their cancer diagnosis and the impact of treatments on their physical and mental well-being. For example, cancer survivors often experience declines in physical functioning and quality of life while facing an increased risk of cancer recurrence and all-cause mortality compared with persons without cancer. The 2010 American College of Sports Medicine Roundtable was among the first reports to conclude that cancer survivors could safely engage in enough exercise training to improve physical fitness and restore physical functioning, enhance quality of life, and mitigate cancer-related fatigue.MethodsA second Roundtable was convened in 2018 to advance exercise recommendations beyond public health guidelines and toward prescriptive programs specific to cancer type, treatments, and/or outcomes.ResultsOverall findings retained the conclusions that exercise training and testing were generally safe for cancer survivors and that every survivor should "avoid inactivity." Enough evidence was available to conclude that specific doses of aerobic, combined aerobic plus resistance training, and/or resistance training could improve common cancer-related health outcomes, including anxiety, depressive symptoms, fatigue, physical functioning, and health-related quality of life. Implications for other outcomes, such as peripheral neuropathy and cognitive functioning, remain uncertain.ConclusionsThe proposed recommendations should serve as a guide for the fitness and health care professional working with cancer survivors. More research is needed to fill remaining gaps in knowledge to better serve cancer survivors, as well as fitness and health care professionals, to improve clinical practice.
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Project description:IntroductionLoss of skeletal muscle mass and function (sarcopenia) is common in individuals with obesity due to metabolic changes associated with a sedentary lifestyle, adipose tissue derangements, comorbidities (acute and chronic diseases) and during the ageing process. Co-existence of excess adiposity and low muscle mass/function is referred to as sarcopenic obesity (SO), a condition increasingly recognized for its clinical and functional features that negatively influence important patient-centred outcomes. Effective prevention and treatment strategies for SO are urgently needed, but efforts are hampered by the lack of a universally established SO definition and diagnostic criteria. Resulting inconsistencies in the literature also negatively affect the ability to define prevalence as well as clinical relevance of SO for negative health outcomes.Aims and methodsThe European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) launched an initiative to reach expert consensus on a definition and diagnostic criteria for SO. The jointly appointed international expert panel proposes that SO is defined as the co-existence of excess adiposity and low muscle mass/function. The diagnosis of SO should be considered in at-risk individuals who screen positive for a co-occurring elevated body mass index or waist circumference, and markers of low skeletal muscle mass and function (risk factors, clinical symptoms, or validated questionnaires). Diagnostic procedures should initially include assessment of skeletal muscle function, followed by assessment of body composition where presence of excess adiposity and low skeletal muscle mass or related body compartments confirm the diagnosis of SO. Individuals with SO should be further stratified into stage I in the absence of clinical complications or stage II if cases are associated with complications linked to altered body composition or skeletal muscle dysfunction.ConclusionsESPEN and EASO, as well as the expert international panel, advocate that the proposed SO definition and diagnostic criteria be implemented into routine clinical practice. The panel also encourages prospective studies in addition to secondary analysis of existing data sets, to study the predictive value, treatment efficacy and clinical impact of this SO definition.
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Project description:Randomized trials support carotid endarterectomy (CEA) in asymptomatic patients with ?60% internal carotid artery (ICA) stenosis. The widely referenced Society for Radiologists in Ultrasound Consensus Statement on carotid duplex ultrasound (CDUS) imaging indicates that an ICA peak systolic velocity (PSV) ?230 cm/s corresponds to a ?70% ICA stenosis, leading to the potential conclusion that asymptomatic patients with an ICA PSV ?230 cm/s would benefit from CEA. Our goal was to determine the natural history stroke risk of asymptomatic patients who might have undergone CEA based on consensus statement PSV of ?230 cm/s but instead were treated medically based on more conservative CDUS imaging criteria.All patients who underwent CDUS imaging at our institution during 2009 were retrospectively reviewed. The year 2009 was chosen to ensure extended follow-up. Asymptomatic patients were included if their ICA PSV was ?230 cm/s but less than what our laboratory considers a ?80% stenosis by CDUS imaging (PSV ?430 cm/s, end-diastolic velocity ?151 cm/s, or ICA/common carotid artery PSV ratio ?7.5). Study end points included freedom from transient ischemic attack (TIA), freedom from any stroke, freedom from carotid-etiology stroke, and freedom from revascularization.Criteria for review were met by 327 patients. Mean follow-up was 4.3 years, with 85% of patients having >3-year follow-up. Four unheralded strokes occurred during follow-up at <1, 17, 25, and 30 months that were potentially attributable to the index carotid artery. Ipsilateral TIA occurred in 17 patients. An additional 12 strokes occurred that appeared unrelated to ipsilateral carotid disease, including hemorrhagic events, contralateral, and cerebellar strokes. Revascularization was undertaken in 59 patients, 1 for stroke, 12 for TIA, and 46 for asymptomatic disease. Actuarial freedom from carotid-etiology stroke was 99.7%, 98.4%, and 98.4% at 1, 3, and 5 years, respectively. Freedom from TIA was 98%, 96%, and 95%, freedom from any stroke was 99%, 96%, and 93%, and freedom from revascularization was 95%, 86%, and 81% at 1, 3, and 5 years, respectively.Patients with intermediate asymptomatic carotid stenosis (ICA PSV 230-429 cm/s) do well with medical therapy when carefully monitored and intervened upon using conservative CDUS criteria. Furthermore, a substantial number of patients would undergo unnecessary CEA if consensus statement CDUS thresholds are used to recommend surgery. Current velocity threshold recommendations should be re-evaluated, with potentially important implications for upcoming clinical trials.
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Project description:Fibrous Dysplasia / McCune Albright syndrome (FD/MAS) represents a wide spectrum of diseases due to somatic gain-of-function mutations of the GNAS gene. The mutation leads to overactivity in the target tissues and to a wide phenotype of clinical features that vary in severity and age of onset. The rarity of the disease and its variable presentation to multiple specialities often leads to misdiagnosis and inappropriate variability in investigations and treatments. To address this, our international consortium of clinicians, researchers, and patients' advocates has developed pragmatic clinical guidelines for best clinical practice for the definition, diagnosis, staging, treatment and monitoring for FD/MAS to empower patients and support clinical teams in both general and specialised healthcare settings. With the lack of strong evidence to inform care, the guidelines were developed based on review of published literature, long-standing extensive experience of authors, input from other healthcare professionals involved in the care of FD/MAS patients and feedback from patients and patient groups across the globe. This has led to the formulation of a set of statements to inform healthcare professionals, patients, their families, carers and patient groups of the best practice of care. It is anticipated the implementation of these recommendations will lead to improvement in the care of patients with FD/MAS internationally.
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Project description:The diagnosis of Waldenström's macroglobulinemia (WM), an IgM-associated lymphoplasmacytic lymphoma, can be challenging due to the different forms of disease presentation. Furthermore, in recent years, WM has witnessed remarkable progress on the diagnostic front, as well as a deeper understanding of the disease biology, which has affected clinical practice. This, together with the increasing variety of tools and techniques available, makes it necessary to have a practical guidance for clinicians to perform the initial evaluation of patients with WM. In this paper, we present the consensus recommendations and laboratory requirements for the diagnosis of WM developed by the European Consortium of Waldenström's Macroglobulinemia (ECWM), for both clinical practice as well as the research/academical setting. We provide the procedures for multiparametric flow cytometry, fluorescence in situ hybridization and molecular tests, and with this offer guidance for a standardized diagnostic work-up and methodological workflow of patients with IgM monoclonal gammopathy of uncertain significance, asymptomatic and symptomatic WM.
| S-EPMC9898035 | biostudies-literature