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Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease.

ABSTRACT: BACKGROUND:Many patients remain without a diagnosis despite extensive medical evaluation. The Undiagnosed Diseases Network (UDN) was established to apply a multidisciplinary model in the evaluation of the most challenging cases and to identify the biologic characteristics of newly discovered diseases. The UDN, which is funded by the National Institutes of Health, was formed in 2014 as a network of seven clinical sites, two sequencing cores, and a coordinating center. Later, a central biorepository, a metabolomics core, and a model organisms screening center were added. METHODS:We evaluated patients who were referred to the UDN over a period of 20 months. The patients were required to have an undiagnosed condition despite thorough evaluation by a health care provider. We determined the rate of diagnosis among patients who subsequently had a complete evaluation, and we observed the effect of diagnosis on medical care. RESULTS:A total of 1519 patients (53% female) were referred to the UDN, of whom 601 (40%) were accepted for evaluation. Of the accepted patients, 192 (32%) had previously undergone exome sequencing. Symptoms were neurologic in 40% of the applicants, musculoskeletal in 10%, immunologic in 7%, gastrointestinal in 7%, and rheumatologic in 6%. Of the 382 patients who had a complete evaluation, 132 received a diagnosis, yielding a rate of diagnosis of 35%. A total of 15 diagnoses (11%) were made by clinical review alone, and 98 (74%) were made by exome or genome sequencing. Of the diagnoses, 21% led to recommendations regarding changes in therapy, 37% led to changes in diagnostic testing, and 36% led to variant-specific genetic counseling. We defined 31 new syndromes. CONCLUSIONS:The UDN established a diagnosis in 132 of the 382 patients who had a complete evaluation, yielding a rate of diagnosis of 35%. (Funded by the National Institutes of Health Common Fund.).

SUBMITTER: Splinter K

PROVIDER: S-EPMC6481166 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease.

Splinter Kimberly K Adams David R DR Bacino Carlos A CA Bellen Hugo J HJ Bernstein Jonathan A JA Cheatle-Jarvela Alys M AM Eng Christine M CM Esteves Cecilia C Gahl William A WA Hamid Rizwan R Jacob Howard J HJ Kikani Bijal B Koeller David M DM Kohane Isaac S IS Lee Brendan H BH Loscalzo Joseph J Luo Xi X McCray Alexa T AT Metz Thomas O TO Mulvihill John J JJ Nelson Stanley F SF Palmer Christina G S CGS Phillips John A JA Pick Leslie L Postlethwait John H JH Reuter Chloe C Shashi Vandana V Sweetser David A DA Tifft Cynthia J CJ Walley Nicole M NM Wangler Michael F MF Westerfield Monte M Wheeler Matthew T MT Wise Anastasia L AL Worthey Elizabeth A EA Yamamoto Shinya S Ashley Euan A EA

The New England journal of medicine 20181010 22

<h4>Background</h4>Many patients remain without a diagnosis despite extensive medical evaluation. The Undiagnosed Diseases Network (UDN) was established to apply a multidisciplinary model in the evaluation of the most challenging cases and to identify the biologic characteristics of newly discovered diseases. The UDN, which is funded by the National Institutes of Health, was formed in 2014 as a network of seven clinical sites, two sequencing cores, and a coordinating center. Later, a central bio ...[more]

PMID: 30304647

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Project description:BACKGROUND: Conventional screening for hypothyroidism is controversial. Although hypothyroidism is underdiagnosed, many organizations do not recommend screening, citing low disease prevalence in unselected populations. We studied attendees at a thyroid health fair, hypothesizing that certain patient characteristics would enhance the yield of testing. METHODS: We carried out an observational study of participants at a Michigan health fair that focused on thyroid disease. We collected patient-reported symptoms and demographics by questionnaire, and correlated these with the TSH values obtained through the health fair. RESULTS: 794 of 858 health fair attendees participated. Most were women, and over 40% reported a family history of thyroid disease. We identified 97 (12.2%) participants with previously unknown thyroid dysfunction. No symptom or combination of symptoms discriminated between hypothyroid and euthyroid individuals. Hypothyroid and euthyroid participants in the health fair reported each symptom with a similar prevalence (p?>?0.01), a prevalence which was very high. In fact, when compared with a previously published case-control study that reported symptoms, the euthyroid health fair participants reported a higher symptom prevalence (range 3.9% to 66.3%, mean 31.5%), than the euthyroid individuals from the case-control study (range 2% to 54%, mean 17.4%). CONCLUSIONS: A high proportion of previously undiagnosed thyroid disease was identified at this health fair. We initially hypothesized symptoms would distinguish between thyroid function states. However, this was not the case in this health fair screening population. The prevalence of reported symptoms was similar and high in both euthyroid and hypothyroid participants. Because attendees were self-selected, it is possible that this health fair that focused on thyroid disease attracted participants specifically concerned about thyroid health. Despite the lack of symptom discrimination, the much higher prevalence of hypothyroidism in this study (12%) compared with the general population (<2%) suggests that screening may be appropriate and effective in certain circumstances such as thyroid health fairs.

Project description:Because osteoporosis is under-recognized in patients with vertebral fractures, we evaluated characteristics associated with osteoporosis identification. Most patients with vertebral fractures did not receive evaluation or treatment for osteoporosis. Black, younger, and male participants were particularly unlikely to have had recognized osteoporosis, which could increase their risk of negative outcomes.IntroductionVertebral fractures may be identified on imaging but fail to prompt evaluation for osteoporosis. Our objective was to evaluate characteristics associated with clinical osteoporosis recognition in patients who had vertebral fractures detected on their thoracolumbar spine imaging reports.MethodsWe prospectively identified individuals who received imaging of the lower spine at primary care clinics in 4 large healthcare systems who were eligible for osteoporosis screening and lacked indications of osteoporosis diagnoses or treatments in the prior year. We evaluated characteristics of participants with identified vertebral fractures that were associated with recognition of osteoporosis (diagnosis code in the health record; receipt of bone mineral density scans; and/or prescriptions for anti-osteoporotic medications). We used mixed models to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs).ResultsA total of 114,005 participants (47% female; mean age 65 (interquartile range: 57-72) years) were evaluated. Of the 8579 (7%) participants with vertebral fractures identified, 3784 (44%) had recognition of osteoporosis within the subsequent year. In adjusted regressions, Black participants (OR (95% CI): 0.74 (0.57, 0.97)), younger participants (age 50-60: 0.48 (0.42, 0.54); age 61-64: 0.70 (0.60, 0.81)), and males (0.39 (0.35, 0.43)) were less likely to have recognized osteoporosis compared to white participants, adults aged 65 + years, or females.ConclusionIndividuals with identified vertebral fractures commonly did not have recognition of osteoporosis within a year, particularly those who were younger, Black, or male. Providers and healthcare systems should consider efforts to improve evaluation of osteoporosis in patients with vertebral fractures.

Dataset Information

Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease.

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Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease.

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