Clinical and Genetic Evaluation of Individuals With Undiagnosed Disorders Through the Undiagnosed Diseases Network

Study Overview
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Brief Summary
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Without an explanation for severe and sometimes life-threatening symptoms, patients and their families are left in a state of unknown. Many individuals find themselves being passed from physician to physician, undergoing countless and often repetitive tests in the hopes of finding answers and insight about what the future may hold. This long and arduous journey to find a diagnosis does not end for many patients- the Office of Rare Diseases Research (ORDR) notes that 6% of individuals seeking their assistance have an undiagnosed disorder. In 2008, the National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) was established with the goal of providing care and answers for these individuals with mysterious conditions who have long eluded diagnosis. The NIH UDP is a joint venture of the NIH ORDR, the National Human Genome Research Institute Intramural Research Program (NHGRI-IRP), and the NIH Clinical Research Center (CRC) (1-3). The goals of the NIH UDP are to: (1) provide answers for patients with undiagnosed diseases; (2) generate new knowledge about disease mechanisms; (3) assess the application of new approaches to phenotyping and the use of genomic technologies; and (4) identify potential therapeutic targets, if possible. To date, the UDP has evaluated 3300 medical records and admitted 750 individuals with rare and undiagnosed conditions to the NIH Clinical Center. The NIH UDP has identified more than 70 rare disease diagnoses and several new conditions. The success of the NIH UDP prompted the NIH Common Fund to support the establishment of a network of medical research centers, the Undiagnosed Diseases Network (UDN), for fiscal years 2013-2020. The clinical sites will perform extensive phenotyping, genetic analyses, and functional studies of potential disease-causing variants. The testing performed on patients involves medically indicated studies intended to help reach a diagnosis, as well as research investigations that include a skin biopsy, blood draws, and DNA analysis. In addition, the UDN will further the goals of the UDP by permitting the sharing of personally identifiable phenotypic and genotypic information within the network. By sharing participant information and encouraging collaboration, the UDN hopes to improve the understanding of rare conditions and advance the diagnostic process and care for individuals with undiagnosed diseases.

Detailed Description
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Without an explanation for severe and sometimes life-threatening symptoms, patients and their families are left in a state of unknown. Many individuals find themselves being passed from physician to physician, undergoing countless and often repetitive tests in the hopes of finding answers and insight about what the future may hold. This long and arduous journey to find a diagnosis does not end for many patients- the Office of Rare Diseases Research (ORDR) notes that 6% of individuals seeking their assistance have an undiagnosed disorder. In 2008, the National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) was established with the goal of providing care and answers for these individuals with mysterious conditions who have long eluded diagnosis. The NIH UDP is a joint venture of the NIH ORDR, the National Human Genome Research Institute Intramural Research Program (NHGRI-IRP), and the NIH Clinical Research Center (CRC). The goals of the NIH UDP are to: (1) provide answers for patients with undiagnosed diseases; (2) generate new knowledge about disease mechanisms; (3) assess the application of new approaches to phenotyping and the use of genomic technologies; and (4) identify potential therapeutic targets, if possible. Prior to formation of the Undiagnosed Diseases Network (UDN), the UDP had evaluated 3300 medical records, admitted 750 individuals with rare and undiagnosed conditions to the NIH Clinical Center, and identified more than 70 rare disease diagnoses and several new conditions. The success of the NIH UDP prompted the NIH Common Fund to support the establishment of a network of medical research centers, the UDN, for fiscal years 2013-2022. The clinical sites perform extensive phenotyping, genetic analyses, and functional studies of potential disease-causing variants. The testing performed on patients involves medically indicated studies intended to help reach a diagnosis, as well as research investigations that include a skin biopsy, blood draws, and DNA analysis. In addition, the UDN is furthering the goals of the UDP by permitting the sharing of personally identifiable phenotypic and genotypic information within the network. By sharing participant information and encouraging collaboration, the UDN hopes to improve the understanding of rare conditions and advance the diagnostic process and care for individuals with undiagnosed diseases.

Official Title
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Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network

Conditions
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Genetic Disease

Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: Ideal applicants to the UDN include individuals with: One or more objective findings pertinent to the phenotype for which a UDN application was submitted. No diagnosis despite evaluation by at least two specialists who assessed the patient for the objective finding(s). Agreement for the storage and sharing of information and biomaterials, in an identified fashion amongst the UDN centers, and in a de-identified fashion to research sites beyond the network. Applicants unable to consent can be enrolled. EXCLUSION CRITERIA: -Applicants who are unlikely to be accepted include individuals with: Reported symptoms with no relevant objective findings. A diagnosis explaining objective findings. A diagnosis suggested on record review. Unwillingness to share data.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Undiagnosed disorders<br>Patients with rare, undiagnosed disorders. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Create an integrated and collaborative research community across multiple clinical sites and between laboratory and clinical investigators prepared to investigate the pathophysiology of these new and rare diseases, the impact of the diagnostic p... | Create an integrated and collaborative research community across multiple clinical sites and between laboratory and clinical investigators prepared to investigate the pathophysiology of these new and rare diseases, the impact of the diagnostic process on patients and families, and share this understanding to identify improved options for optimal patient management. | Day 1-5 and followup | 
| Facilitate research into the etiology of undiagnosed diseases, by collecting and sharing standardized, high-quality clinical and laboratory data including genotyping, phenotyping, and documentation of environmental exposures | Facilitate research into the etiology of undiagnosed diseases, by collecting and sharing standardized, high-quality clinical and laboratory data including genotyping, phenotyping, and documentation of environmental exposures. | Day 1-5 and followup | 
| Improve the level of diagnosis and care for patients with undiagnosed diseases through the development of common and site-specific protocols designed by an enlarged community of investigators | Improve the level of diagnosis and care for patients with undiagnosed diseases through the development of common and site-specific protocols designed by an enlarged community of investigators. | Day 1-5 and followup | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rare Diseases, Undiagnosed Diseases, Natural History