Good to know
- Genetic testing is transforming care for people with rare diseases by helping clinicians identify the underlying causes of complex, often life‑limiting conditions and end prolonged diagnostic journeys for patients and families.
- At UHN, advanced genomic testing enables clinicians to pinpoint disease‑causing variants, improving diagnostic accuracy and guiding decisions about monitoring, prevention and treatment.
The zebra has a poignant meaning for people living with rare diseases.
There's a well-known medical adage — "When you hear hoof beats, think horses, not zebras" — that reminds clinicians common conditions are usually the most likely explanation for a patient's symptoms.
Advocacy groups — like the
Canadian Organization for Rare Disorders — have adopted the striped equine as a symbol of these uncommon conditions and the effort to improve awareness, treatment and research.
At UHN, the Division of Clinical Genomics combines advanced genetic testing with specialized expertise to uncover the causes of rare and unexplained conditions for patients across Ontario and Canada, offering long-sought answers and a path toward potentially life-changing treatments.
What is a rare disease?
Rare diseases aren't rare when you add them all up. More than 300 million people worldwide, including three million Canadians, live with one. There is no single internationally accepted definition, but a disease is generally considered rare if it affects less than one in 2,000 individuals.
Rare diseases can take many forms, including genetic conditions, metabolic disorders, cancers, blood disorders and autoimmune diseases. These illnesses are typically serious, complex and life limiting. They often begin in childhood, making an early, accurate diagnosis especially important, although some don't appear until adulthood.
Why diagnosing rare diseases is difficult and how genomics help
Clinicians may encounter certain rare diseases only once in their careers, and symptoms often resemble far more common conditions. Diagnosis often begins by ruling out these conditions before consulting specialists, which can lead many patients through a lengthy diagnostic odyssey.
About 80 per cent of rare diseases are genetic. Genomic testing has become central to diagnosis, allowing clinicians to pinpoint the genetic variant and determine whether it was inherited or arose spontaneously.
"Genetics underpins the vast majority of rare diseases, and the ability to analyze DNA has advanced enormously in the last 25 years," says Dr. Kathy Siminovitch, medical director of UHN's Division of Clinical Genomics. "Genomic testing now gives us far clearer answers, transforming how quickly and accurately we can reach a diagnosis."
How does genomic testing work?
Clinicians consider genomic testing when symptoms involve multiple organ systems, when family history points to an inherited condition or when standard testing does not yield answers. A medical geneticist and a genetic counsellor determine the appropriate strategy, which can focus on a single gene or involve whole-genome sequencing.
UHN's Division of
Clinical Laboratory Genetics performs more than 30,000 tests annually, including the largest clinical cancer genetics testing service in Canada. Some very rare cases are sent to specialized international laboratories.
DNA is extracted from a sample — usually blood, but sometimes saliva or cells collected with a cheek swab. Machines then compare the sample against reference sequences to identify variants.
How genetic information shapes rare disease care for patients
Genetic testing isn't just about finding an answer — it's about using that answer to guide care. Identifying variants helps clinical teams adjust therapies, anticipate health risks and plan long-term monitoring.
"Knowing someone is genetically at risk lets us intervene earlier and take steps to prevent complications," says Jillian Murphy, clinic manager at the Fred A. Litwin Family Centre in Genetic Medicine.
She cites phenylketonuria (PKU), a condition where the body cannot properly break down a common amino acid. Diagnosis leads directly to specialized diets and regular monitoring.
A genetic diagnosis offers a practical roadmap, identifying which specialty should lead follow up and when to involve additional clinical teams. The results can prompt testing of at-risk relatives, even if they have no symptoms, and provide clear guidance on what to monitor over time. Multidisciplinary care is delivered by geneticists, genetic counsellors, dietitians, nurses and social workers who collaborate with other specialists across UHN to tailor care to each patient's medical and psychosocial needs.
Across UHN, genetic counsellors support a range of specialty programs — from cardiac genetics at the
Peter Munk Cardiac Centre to the GoodHope Ehlers–Danlos Syndrome Clinic to the Elisabeth Raab Neurofibromatosis Clinic — bringing genetics expertise into the clinics where patients already receive care.
For conditions such as Fabry disease or Gaucher disease, genetic findings directly shape care — including enzyme replacement therapy — and guide long-term follow up. Many of these patients transition from pediatric care at SickKids Hospital, reflecting the long‑term nature of rare‑disease care.
What does treatment look like for rare diseases?
Genomics helps explain the "why," but treatment depends on the network of teams who turn that information into long-term, co-ordinated care, drawing on specialist expertise, as well as opportunities to take part in clinical trials.
Many rare diseases affect more than one organ system, so understanding the underlying genetics helps clinicians predict which areas need closer surveillance. For example, a condition like porphyria can cause both gastrointestinal and neurological symptoms, depending on the subtype. Knowing the genetic variant determines whether the patient is followed by gastroenterology, neurology or both, and what complications to watch for.
Individually, rare diseases are uncommon. But taken together they affect millions, creating a need that far exceeds what their name suggests. Effective care depends not only on identifying the genetic cause, but on integrating that knowledge into clinical practice and supporting patients across specialties over the long term.
