PhenomeCentral: A Tool for Improving Rare Disease Diagnosis

PhenomeCentral: A Tool for Improving Rare Disease Diagnosis

Ian Stedman was born with a rare disease, but it wasn’t until he was 32 that he received a correct diagnosis. When Stedman was a child, he was plagued by persistent rashes, severe joint pain, and headaches that caused him to miss out on school and other activities.1 Stedman spent years going from clinic to clinic trying to get a diagnosis for his condition, but he never got one. Stedman accepted his symptoms and lived with them until his daughter was born with the same distinctive rashes. Stedman took matters into his own hands and did his own research using the symptoms he had experienced as a basis for his search. Eventually Stedman came across Muckle-Wells Syndrome, a disease so rare its prevalence is unknown. Stedman got in contact with Ronald Laxer, one of two specialists in Canada. Stedman took a genetic test, which came back positive for Muckle-Wells syndrome. The diagnosis has lifted a weight off of Stedman’s shoulders as he has started treatment and knows it will be available for his daughter, saving her from the pain he experienced.


“In Canada, it takes an average of seven years to obtain a correct diagnosis and treatment plan...”

In Canada, it takes an average of seven years to obtain a correct diagnosis and treatment plan, and this process takes a major toll on a patient’s well being.2 There are many reasons a rare disease patient can go so long without a correct diagnosis. Firstly, doctors are trained with the refrain: “When you hear hoofbeats, think horses, not zebras.”1 This refrain is taught because usually, the most common condition is the correct diagnosis, but this rationale can make getting a rare disease diagnosis difficult. A lack of diagnosis takes a toll on the patient and their family. Consequently, the patient, typically a child, has to live with the burden of a disease that continues to go untreated. Furthermore, parents have to deal with the stress and isolation of not knowing what is causing the symptoms, or how long their child will live.3 The search for a diagnosis is a time-consuming and costly process, and in some cases, patients need to fly to a different province or to the US to get a proper diagnosis. The good news is that Canada has efforts in place to reduce the wait for a diagnosis with research programs and technological advances.4


In Canada, programs such as newborn screening and genetic research funding help increase rare disease diagnosis. Every province has newborn screening, which can be used to identify rare diseases in newborns and improve outcomes.5 Canada also has programs to incentivize research on rare diseases, which can help facilitate a quicker diagnosis. Many rare diseases are genetic and programs that increase genetic research, such as Canadian Institutes of Health Research, can increase the understanding of genetic diseases.5 Additionally, initiatives like the Finding of Rare Disease Genes (FORGE), a Canadian consortium of clinicians and scientists, have increased understanding of rare genetic diseases. In a two-year period, FORGE studied 264 diseases and was able to identify genetic variants in 146 of them, 67 of which were not previously associated with a human disease.6 Large-scale projects such as FORGE can improve understanding of the genetics that cause rare diseases and improve diagnosis.


Recently, there has been a new tool used to improve diagnosis of rare diseases: genotype and phenotype matching software. This technology has been unified by the Matchmaker Exchange (MME), which developed an algorithm to identify similar cases by matching patients entries with similar phenotypes and genomes.7 This can allow for the clinician who entered the information to make a better informed diagnosis of the patient. Additionally, it allows for collaboration between clinicians and scientists to increase knowledge about rare diseases. There are multiple platforms that use MME, and one, called PhenomeCentral was created in Canada at the University of Toronto in 2014.8 PhenomeCentral is a matchmaking software that identifies similar patients from either a hypothesis-free or hypothesis-driven perspective.8 The clinician enters their patient’s phenotypic description and genetic information into the database which uses the MME algorithm to find similar cases. This kind of software is extremely helpful because it can be very difficult to find other patients with similar indications, and data sharing allows for more accurate diagnosis.


There are some concerns associated with matchmaker software, such as privacy and lack of a universal diagnosis vocabulary. The program has different levels of privacy to allow patients to control who can access their information.8 The private setting does not share any data with other users. The matchable setting makes the data visible to others but the patient and clinician cannot be discovered. The public setting allows all registered users (clinicians and researchers) to access the information and the submitter’s contact details. These setting are very important to allow the patients to feel secure about their personal information. Another important consideration for this software is wording used by clinicians. The program is based on an automated algorithm, so it is important that a unified language is used for describing patient phenotype. The Human Phenotype Ontology (HPO) is the most complete vocabulary available for describing phenotypes, and if used as the standard for all clinicians will allow for precise descriptions.8 Despite the perceived risks of using a software for patient matching, there are provisions in place to make the use of PhenomeCentral a success.


“Since its release in 2014, PhenomeCentral currently has grown to 1,176 members, thousands of cases, and is continuing to grow.”

Since its release in 2014, PhenomeCentral currently has grown to 1,176 members, thousands of cases, and is continuing to grow.9 Most contributors are from Canada, the US, and the EU, but the program continues to grow. Often rare disease gene finding projects, such as FORGE, will contribute many useful entries to the database.8 When researcher projects contribute knowledge about genes linked to rare diseases, clinicians can use this data to make better informed diagnoses. Additionally, the wide range of members increases the chances of finding a match, which also contributes to improved rare disease diagnosis.


“Developments like PhenomeCentral are integral to creating a relationship between the research community and clinicians.”

Developments like PhenomeCentral are integral to creating a relationship between the research community and clinicians. As clinicians enter data about rare disease phenotype and genotypes, researchers can gather this data and study it to better understand rare diseases. As researchers publish more findings on these rare diseases, clinicians will be able to use that information to make more informed diagnoses, creating a positive feedback loop. PhenomeCentral also has positive impacts on the undiagnosed patient population by increasing the ability of clinicians to make a correct diagnosis. When a correct diagnosis is made, it relieves the patient and their family of the confusion and stress that come with being undiagnosed, and allows the patient to start treatment. Continued development of these innovative software will have a positive impact on the rare disease community, in Canada and around the world.


Works Cited:

1. Glauser W, Stasiuk M, Taylor M. When it’s a zebra: Does Canada need a rare disease strategy?. Healthy Debate. http://healthydebate.ca/2015/11/topic/rare-diseases-undiagnosed-national-strategy. Published 2015.

2. Canadian Organization for Rare Disorders. Now Is The Time: A Strategy For Rare Diseases Is A Strategy For All Canadians.; 2015. Available at: http://www.raredisorders.ca/content/uploads/CORD_Canada_RD_Strategy_22May15.pdf.

3. EURODIS, SWAN UK, The Wilhelm Foundation, Rare Voices Australia, CORD, ASrid, NORD. International Joint Recommendations To Address Specific Needs Of Undiagnosed Rare Disease Patients.; 2016. Available at: http://download.eurordis.org.s3.amazonaws.com/documents/pdf/Undiagnosed-International-Joint-Recommendations.pdf.

4. Zonneville J. Exploring the Impact of Canada's Healthcare Research Footprint on Rare Diseases. Market Wired. http://www.marketwired.com/press-release/exploring-the-impact-of-canadas-healthcare-research-footprint-on-rare-diseases-2079452.htm. Published 2015.

5. Critical Care Services Ontario. Rare Diseases Working Group Report.; 2017. Available at: http://www.health.gov.on.ca/en/common/ministry/publications/reports/rare_diseases_2017/rare_diseases_report_2017.pdf.

6. Beaulieu C, Majewski J, Schwartzentruber J et al. FORGE Canada Consortium: Outcomes of a 2-Year National Rare-Disease Gene-Discovery Project. The American Journal of Human Genetics. 2014;94(6):809-817. doi:10.1016/j.ajhg.2014.05.003.

7. Philippakis A, Azzariti D, Beltran S et al. The Matchmaker Exchange: A Platform for Rare Disease Gene Discovery. Hum Mutat. 2015;36(10):915-921. doi:10.1002/humu.22858.

8. Buske O, Girdea M, Dumitriu S et al. PhenomeCentral: A Portal for Phenotypic and Genotypic Matchmaking of Patients with Rare Genetic Diseases. Hum Mutat. 2015;36(10):931-940. doi:10.1002/humu.22851.

9. Dumitriu S. About PhenomeCentral | PhenomeCentral. Phenomecentralorg. 2018. Available at: https://www.phenomecentral.org/About#HDiscoveringsimilarcasesinPhenomeCentral.


Cite This Article:

Smith E., Chan G., Palczewski K., Lewis K., Ho J. PhenomeCentral: A Tool for Improving Rare Disease Diagnosis. Illustrated by R. Michaels-Walker. Rare Disease Review. February 2019. DOI:10.13140/RG.2.2.27557.35048.

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