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

June 10, 2026 updated by: National Human Genome Research Institute (NHGRI)

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

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.

Study Overview

Status

Recruiting

Conditions

Detailed Description

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.1-3 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, 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.

Study Type

Observational

Enrollment (Estimated)

20000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • University of Alabama at Birmingham
        • Contact:
      • Huntsville, Alabama, United States, 35806
        • Completed
        • HudsonAlpha Institute for Biotechnology, Inc.
    • California
      • Los Angeles, California, United States, 90095
        • Recruiting
        • University of California, Los Angeles
        • Contact:
      • Orange, California, United States, 92668
        • Recruiting
        • University of California, Irvine Medical Center
        • Contact:
      • Stanford, California, United States, 94305
        • Recruiting
        • Leland Stanford Junior University
        • Contact:
      • Stanford, California, United States, 94305
        • Recruiting
        • Stanford Hospital and Clinics
        • Contact:
      • Stanford, California, United States, 94020
        • Completed
        • Lucile Salter Packard Children's Hospital at Stanford
      • Stanford, California, United States, 94305-5584
        • Recruiting
        • Stanford University
        • Contact:
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
    • Florida
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami Miller School of Medicine
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Not yet recruiting
        • Lurie Children s Hospital
        • Contact:
    • Indiana
      • Indianapolis, Indiana, United States, 46202-5262
        • Recruiting
        • Indiana University
        • Contact:
          • Stephane Ware, M.D.
          • Phone Number: 317-274-8938
          • Email: stware@iu.edu
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • Recruiting
        • National Institutes of Health Clinical Center
        • Contact:
          • For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)
          • Phone Number: TTY dial 711 800-411-1222
          • Email: ccopr@nih.gov
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Brigham and Women's Hospital
        • Contact:
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
      • Boston, Massachusetts, United States, 02115
      • Boston, Massachusetts, United States, 02115
        • Not yet recruiting
        • Harvard U Faculty of Medicine
        • Contact:
      • Boston, Massachusetts, United States, 02115
        • Completed
        • Harvard T.H. Chan School of Public Health
    • Minnesota
      • Rochester, Minnesota, United States, 55905
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University in St. Louis
        • Contact:
    • New York
      • New York, New York, United States, 10013
        • Active, not recruiting
        • New York Genome Center
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University Health System
        • Contact:
    • Oregon
      • Eugene, Oregon, United States, 97403
        • Not yet recruiting
        • University of Oregon
        • Contact:
      • Portland, Oregon, United States, 97201-3098
        • Completed
        • Oregon Health Sciences University
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Children's Hospital of Philadelphia
        • Contact:
      • Philadelphia, Pennsylvania, United States, 19104-6056
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt University Medical Center
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Baylor College of Medicine
        • Contact:
          • Brendan Lee, M.D.
          • Phone Number: 713-798-8835
          • Email: blee@bcm.edu
    • Utah
      • Salt Lake City, Utah, United States, 84112
    • Washington
      • Richland, Washington, United States, 99354
        • Completed
        • Pacific Northwest National Laboratory
      • Seattle, Washington, United States, 98195
        • Recruiting
        • University of Washington
        • Contact:
          • Gail Jarvik, M.D.
          • Phone Number: Not Listed
          • Email: pair@uw.edu
      • Seattle, Washington, United States, 98101
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 100 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Individuals with undiagnosed conditions

Description

  • INCLUSION CRITERIA:

Ideal participants for tier 2-4 evaluations include individuals with:

  • One or more objective findings pertinent to the phenotype for which a case was submitted.
  • No diagnosis despite evaluation by 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.

Participants unable to consent can be enrolled.

EXCLUSION CRITERIA:

Individuals who are unlikely to be assigned to tier 2-4 evaluations include those with:

  • Reported symptoms with no relevant objective findings.
  • A diagnosis explaining objective findings.
  • A diagnosis suggested on record review.
  • Unwillingness to share data.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Undiagnosed disorders
Patients with rare, undiagnosed disorders.

What is the study measuring?

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...
Time Frame: Day 1-5 and followup
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
Time Frame: 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.
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
Time Frame: 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.
Day 1-5 and followup

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Human Genome Research Institute (NHGRI)

Investigators

  • Principal Investigator: William A Gahl, M.D., National Human Genome Research Institute (NHGRI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 16, 2015

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

May 19, 2015

First Submitted That Met QC Criteria

May 19, 2015

First Posted (Estimated)

May 21, 2015

Study Record Updates

Last Update Posted (Actual)

June 11, 2026

Last Update Submitted That Met QC Criteria

June 10, 2026

Last Verified

June 9, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 150130
  • 15-HG-0130

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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