Skip to main content


University of Utah Health's Penelope Program for Rare and Undiagnosed diseases is dedicated to solving some of most complex medical cases in our community. Finding answers can unlock better care, novel therapies, and helpful connections with others facing similar circumstances.

The Penelope Program

Undiagnosed diseases are some of the most daunting challenges in medicine. Families often spend years—if not decades—searching for answers to the mysterious illnesses affecting their children. Responding to this challenge, the U of U Health in 2015 launched the Penelope Program.  

The Penelope Program is a collaboration between the Department of Pediatrics, the Department of Human Genetics, ARUP Laboratories, Utah Center for Genetic Discovery, Center for Genomic Medicine, and Primary Children’s Hospital. 

Team, Technology, Access. The core of the Penelope Program is its team of experienced clinicians from multiple specialties, molecular geneticists, data scientists, and researchers. Their pooled cognitive expertise -- their knowledge and experience -- helps evaluate the family and child from different angles and perspectives, to identify potential diagnoses and develop a global diagnostic plan. Prior testing and clinical records are carefully reviewed and assembled, and each case is discussed in depth. 

The team has access to advanced technologies, and diagnostic tools, including some that are not yet clinically available, to push the envelope of discovery. The team can reanalyze prior genetic testing using novel tools, looking for diagnoses that may have been missed. New testing, such as whole genome sequencing and RNA sequencing, can unmask genetic causes hidden in the depths of a complex genome. 

The program is actively engaged in increasing access and reducing disparities in the field of rare and undiagnosed diseases. We will work with families to support the evaluation and diagnostic testing of children regardless of health insurance coverage.  The Penelope program is committed to the notion that genetic evaluation and diagnosis should be available regardless of means.

Generous support. Philanthropic donations support the Penelope Program. We are particularly grateful to Mark and Katie Miller. Their generous support for the program helps us serve and support families who otherwise would not have had access to these services.  

One in a Million

A glowing example of translation between medical discovery and intervention, the Penelope Program uses the power of genomic medicine to end suffering and improve quality of life. 

How to Apply

WHO CAN APPLY. The Penelope Program currently focuses on children with serious, complex conditions who remain without a diagnosis despite multiple evaluations.  

  • Based on many years of experience, we have seen that certain elements increase the change of a successful evaluation:
    • Having clear objective findings (by clinical assessment, laboratory testing, imaging, etc.). A thoughtful referral letter from the provider highlighting these findings is invaluable. 
    • Committed family and referring provider, willing to partner with the Penelope program for the duration of the evaluation. This means, for example, prompt communications, sharing of past records, and willingness to be tested to help diagnose their child.   
  • Additional elements that increase the chance of identifying a genetic cause include having a positive family history (one or more other family members with a similar presentation), early onset (the condition was identified early in life) and having both biologic parents also available for testing. However, these are not essential requirements to apply. 

Because of the significant commitment and cost associated with these evaluations, the program can see a limited number of families every year. We review in detail every referral, including associated medical records. We may request further information if needed. 

For those families who are not entered into the program, we typically provide diagnostic recommendations and suggestions. For example, if a child has not seen a medical geneticist or a specific specialist in the past, we may recommend such clinical evaluations, prior to considering further the referral.  

HOW TO APPLY. To expedite the evaluation, we ask that the referral come from the family’s healthcare provider, in the form of a detailed letter summarizing the clinical history, past testing, and reason for the referral.  This letter can be emailed to  

Some points to note. 

  • A sample referral document can be found here. A complete, detailed letter will make the evaluation much more efficient.  An accompanying letter from the family can be added but is not essential at this stage. However, we ask that the provider first discuss the referral with the family to be sure they are willing to commit to the evaluation. This will save time and effort in the long run. 
  • The referring provider can be their primary care provider or one of the specialists caring for the child (e.g., their neurologist, cardiologist, hematologist, etc.). 
  • If the provider is unsure about the referral or would like to discuss the possibility of referral, they are welcome to contact the program at


The Penelope Program also functions as the core of University of Utah’s Intermountain West site for the Undiagnosed Diseases Network (UDN). The UDN is a national research program for undiagnosed diseases funded by the National Institutes of Health. This program runs in parallel with the Penelope Program, with some differences. 

  • It accepts applications from both adults and children
  • Serves a large geographic area in the Intermountain West
  • It is time-limited (it is based on a grant currently ending in early summer of 2024)
  • Can accept a relatively small number of referrals. 
  • Families can apply through the UDN website, together with a letter from the referring provider

We encourage providers who are unsure whether to refer to the Penelope Program or the UDN’s clinical site to contact us, so we can discuss options and answer questions. 

The Best Care that Science and Medicine Has to Offer

Digital Pedigree CGM

What to expect in the evaluation. The Penelope Program leverages U of U Health’s strengths in medical genetics, many subspecialties, and state-of-the-art DNA analysis. Patients take part in a thorough evaluation that includes:

  • a complete clinical history review
  • medical examinations with detailed phenotyping by multiple specialists 
  • advanced genetic testing including genome sequencing or RNA analysis.

With this information, our experts collaborate to arrive at an in-depth understanding of each patient’s condition with the goal of finding an underlying cause and improving care.

This medical evaluation is just the beginning. A core mission of the program is an enduring commitment to patients and their families. While not all patients receive a definitive answer immediately, sometimes a diagnosis becomes possible as science advances. With this in mind, patient cases are re-reviewed periodically. Our staff further assist families by connecting them with social, community and support services.


Your generous donation to support rare and undiagnosed disease research will not only help find answers for patients and their families, but will also go toward developing new treatments, and maybe even a cure. There are many ways your gift can support genomic medicine and research.


Partnering to Make a Difference

Our physicians and researchers are changing the way rare and undiagnosed diseases are diagnosed and treated, and advancing our understanding of health and disease.

The Penelope Program is a proud partnership between:

Penelope Program Partners Team Portrait

Penelope Program Team

Penelope Team Jan 2024