Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database

Wakap, Stéphanie Nguengang; Lambert, Deborah; Olry, Annie; Rodwell, Charlotte; Gueydan, Charlotte; Lanneau, Valérie; Murphy, Daniel N.; Cam, Yann Le; Rath, Ana

doi:10.1038/s41431-019-0508-0

Cited by 785 publications

(549 citation statements)

References 20 publications

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“…For instance in general care settings, the rare-disease prevalence data from Orphanet could be used. 40 LIRICAL is implemented as a standalone Java desktop application that can be installed in less than an hour. LIRICAL is freely available for academic use and source code can be downloaded from https://github.com/TheJacksonLaboratory/LIRICAL.…”

Section: Discussionmentioning

confidence: 99%

Interpretable Clinical Genomics with a Likelihood Ratio Paradigm

Robinson

Ravanmehr

Jacobsen

et al. 2020

Preprint

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Human Phenotype Ontology (HPO)-based analysis has become standard for genomic diagnostics of rare diseases. Current algorithms use a variety of semantic and statistical approaches to prioritize the typically long lists of genes with candidate pathogenic variants. These algorithms do not provide robust estimates of the strength of the predictions beyond the placement in a ranked list, nor do they provide measures of how much any individual phenotypic observation has contributed to the prioritization result. However, given that the overall success rate of genomic diagnostics is only around 25-50% or less in many cohorts, a good ranking cannot be taken to imply that the gene or disease at rank one is necessarily a good candidate. Likelihood ratios (LR) are statistics for summarizing diagnostic accuracy, providing a measure of how much more (or less) a patient with a disease has a particular test result compared to patients without the disease. Here, we present an approach to genomic diagnostics that exploits the LR framework to provide an estimate of (1) the posttest probability of candidate diagnoses; (2) the LR for each observed HPO phenotype, and (3) the predicted pathogenicity of observed genotypes. LIkelihood Ratio Interpretation of Clinical AbnormaLities (LIRICAL) placed the correct diagnosis within the first three ranks in 92.9% of 384 cases reports comprising 262 Mendelian diseases, with the correct diagnosis having a mean posttest probability of 67.3%. Simulations show that LIRICAL is robust to many typically encountered forms of genomic and phenomic noise. In summary, LIRICAL provides accurate, clinically interpretable results for phenotype-driven genomic diagnostics.

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Section: Discussionmentioning

confidence: 99%

Interpretable Clinical Genomics with a Likelihood Ratio Paradigm

Robinson

Ravanmehr

Jacobsen

et al. 2020

Preprint

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“…We found that 69% of RD patients surveyed were diagnosed in adulthood. This is a striking disparity considering 75% of RDs start in the paediatric period [4]. This may be accounted for by a bias of the selection of the diseases for the survey; 8 of the 22 diseases are exclusively of adult onset.…”

Section: Discussionmentioning

confidence: 99%

“…Collectively, they pose a significant economic burden [1][2][3]. The greater than 6100 known RDs are estimated to affect 3.5-5.9% of the population (excluding rare cancers and infectious diseases) equating to 263-446 million persons globally [4] and approximately 300,000 Irish people. 72% of RDs are genetic and 75% of RDs have paediatric onset [4].…”

Section: Introductionmentioning

confidence: 99%

“…The greater than 6100 known RDs are estimated to affect 3.5-5.9% of the population (excluding rare cancers and infectious diseases) equating to 263-446 million persons globally [4] and approximately 300,000 Irish people. 72% of RDs are genetic and 75% of RDs have paediatric onset [4]. However, the true prevalence of only a few rare disease in Ireland is unknown as there is currently no national RD registry and there are Niall Byrne and Jacqueline Turner both authors are joint first authors as they contributed equally to the manuscript.…”

Section: Introductionmentioning

confidence: 99%

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The role of primary care in management of rare diseases in Ireland

Byrne¹,

Turner²,

Marron³

et al. 2020

Ir J Med Sci

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Background 'Slaintecare' aims to address complex patient care needs in an integrated fashion with an emphasis on patientcentred, patient-empowered community care.Currently there is a lack of knowledge of the impact of rare disease management in primary care and of the information tools required by general practitioners to deliver integrated care for rare disease patients. Aims To complete a pilot survey to estimate the general practice clinical workload attributable to selected rare diseases and assess the use of relevant information sources. Methods A retrospective cross-sectional survey was carried out of general practice consultations (2013-2017) for patients with 22 commonly recognised rare diseases. Results Around 31 general practitioners from 10 Irish practices completed information on 171 patients with rare diseases over 3707 consultations. General practice-specific coding systems were inadequate for rare disease patient identification. Over 139 (81.3%) patients were adult, and 32 (18.7%) were children. Management of care was hospital and not primary care based in 63%. Those eligible for state-reimbursed care had a significantly higher median number of consultations (23 consultations, IQR = 13-37, or 5.8 consultations/year) than those who paid privately (10 consultations, IQR = 4-19, or 2.5 consultations/year) (p < 0.005).General practitioners had access to public information resources on rare diseases but few had knowledge of (35.5%), or had ever used (12.9%) Orphanet, the international rare disease information portal. Conclusions Both specific rare disease-specific coding and use of the relevant rare disease information sources are lacking in general practice in Ireland.

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“…Patients with genetic diseases are common in general practice. Rare diseases, for example, 80% of which have a genetic basis (Institute of Medicine Committee on Accelerating Rare Diseases Research and Orphan Product 2010), may be individually rare but are collectively common with an estimated prevalence of 3.5-5.9% (Nguengang Wakap et al 2019). General practitioners play a pivotal role in identifying, supporting and managing patients and their families with inherited disorders, and as the largest group of clinicians working in the NHS, with 54,024 licenced GPs in England andScotland in 2016 (GMC 2018), will be expected to play a greater role in frontline genetic and genomic services.…”

Section: Introductionmentioning

confidence: 99%

How genomic information is accessed in clinical practice: an electronic survey of UK general practitioners

et al. 2020

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Genomic technologies are having an increasing impact across medicine, including primary care. To enable their wider adoption and realize their potential, education of primary health-care practitioners will be required. To enable the development of such resources, understanding where GPs currently access genomic information is needed. One-hundred fifty-nine UK GPs completed the survey in response to an open invitation, between September 2017 and September 2018. Questions were in response to 4 clinical genomic scenarios, with further questions exploring resources used for rare disease patients, direct-to-consumer genetic testing and collecting a family history. Respondents were most commonly GP principals (independent GPs who own their clinic) (64.8%), aged 35-49 years (54%), worked as a GP for more than 15 years (44%) and practiced within suburban locations (typically wealthier) (50.3%). The most popular 'just in time' education source for all clinical genomic scenarios were online primary care focussed resources with general Internet search engines also popular. For genomic continuous medical education, over 70% of respondents preferred online learning. Considering specific scenarios, local guidelines were a popular resource for the familial breast cancer scenario. A large proportion (41%) had not heard of Genomics England's 100,000 genome project. Few respondents (4%) would access rare disease specific Internet resources (Orphanet, OMIM). Twenty-five percent of respondents were unsure how to respond to a direct-to-consumer commercial genetic test query, with 41% forwarding such queries to local genetic services. GPs require concise, relevant, primary care focussed resources in trusted and familiar online repositories of information. Inadequate genetic education of GPs could increase burden on local genetic services.

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Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database

Cited by 785 publications

References 20 publications

Interpretable Clinical Genomics with a Likelihood Ratio Paradigm

Interpretable Clinical Genomics with a Likelihood Ratio Paradigm

The role of primary care in management of rare diseases in Ireland

How genomic information is accessed in clinical practice: an electronic survey of UK general practitioners

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