Rare Disease - CHEO Research Institute

Care4Rare is a nation-wide research program focusing on the improvement of both the diagnosis and treatment of rare diseases. Led out of the Children’s Hospital of Eastern Ontario (CHEO) Research Institute, CARE for RARE includes 21 academic sites across the country, and is recognized internationally as a pioneer in the field of genomics and personalized medicine.

Its team uses state of the art DNA sequencing technology to identify new rare disease genes for patients across Canada and around the world, and develops novel therapeutic approaches. Together, 80 physicians and 50 scientists work to advance rare disease research as part of the CARE for RARE program.

Currently, 25% rare disease patients wait 5-30 years for a diagnosis; 40% initially receive a misdiagnosis, and half will never receive a diagnosis. In contrast, the evidence-based approach being developed by CARE for RARE will result in an accurate rapid diagnosis for many affected by rare disease. Securing a clear diagnosis means that patients and families can make future projections about their healthcare, tap into best practice guidelines, seek reproductive counselling, and potentially start therapies.

In addition, only 5% of children with rare disease have access to an effective treatment. By investigating approved drugs for effectiveness in other diseases, CARE for RARE hopes to identify novel therapies for some of those currently without any treatment.

More information is also available at the Care4rare web page.

Research Projects

Assessment of longitudinal bone growth in osteogenesis imperfecta using metacarpophalangeal pattern profiles
27/07/2020

COL1A1 and COL1A2 mutations affect bone growth not only by inducing fractures and bone deformities, but also through longitudinal growth deficits in bones that do not fracture or deform.
Utility and practice of electrodiagnostic testing in the pediatric population: An AANEM consensus statement
02/11/2019

The panel found that electrodiagnostic studies continue to have high utility for the diagnosis of numerous childhood neuromuscular disorders, and that standardized approaches along with the use of high‐quality reference values are important to maximize the diagnostic yield of these tests in infants, children, and adolescents.
ALU transposition induces familial hypertrophic cardiomyopathy
01/09/2019

Our results demonstrate that haploinsufficiency resulting from MYBPC3 complete deletion, potentially mediated by Alu recombination, is an important disease mechanism in cardiomyopathy and emphasizes the importance of copy number variation analysis in patients clinically suspected of HCM.
Epilepsy genetics: Current knowledge, applications, and future directions
01/07/2018

Drug screening with in vitro and in vivo models of epilepsy can potentially facilitate new treatment strategies.
Benefits of early referral to pediatric palliative care for a child with a rare disease
01/06/2018

This case is described to provide a voice for families who are caring for a child with an undiagnosed or life-limiting illness and especially for the families who won’t consider PPC either out of fear or not knowing it exists.
Iron Overload In Transfusion-Dependent Survivors Of Hemoglobin Bart’s Hydrops Fetalis
03/05/2018

While homozygous α0-thalassemia is currently considered a rare disease, its prevalence is likely to rise given the high α0-thalassemia gene carrier rates in Southeast Asia coupled with recent advances in fetal medicine that is delivering improved access to intra-uterine transfusions.
Addressing Challenges in the Diagnosis and Treatment of Rare Genetic Diseases
01/03/2018

Here, we discuss the increasing opportunity for diagnosis and therapy of rare diseases and how to tackle the associated challenges.
International Cooperation to Enable the Diagnosis of All Rare Genetic Diseases
05/05/2017

Provision of a molecularly confirmed diagnosis in a timely manner for children and adults with rare genetic diseases shortens their "diagnostic odyssey," improves disease management, and fosters genetic counseling with respect to recurrence risks while assuring reproductive choices.
Utility of whole‐exome sequencing for those near the end of the diagnostic odyssey: time to address gaps in care
01/03/2016

In the next decade we will witness a paradigm shift in the way we care for patients with rare genetic diseases, addressing a significant gap in the management of individuals with rare diseases. The diagnostic journey for patients will include clinical genomic sequencing, which in the not too distant future will be WGS as costs decrease with new platforms. The accessibility of WGS‐based diagnostics for patients will be central to understanding the complete compendium of human genetic pathology. Strategies and infrastructure should be put in place to facilitate discovery in clinical settings, and to further mine large phenotypic and genomic datasets for disease mechanisms. As we understand the etiology of more rare diseases, it is probable that we will increasingly implicate known genes and that the approach to the completion of the complete Mendelian dataset will be asymptotic. There will be a subset of rare diseases that are due to non‐coding mutations in regulatory regions that may be more readily identified with the imminent use of WGS and RNA sequencing, and to implicate and understand this type of variation will require large‐scale data sharing at an impressive level. Ultimately, such datasets will be instrumental in identifying modifiers of disease, providing insight into phenotypic variability, prognosis, and for a subset of diseases, identifying drug targets. Finally, NGS technologies are providing significant opportunities to implement personalized health strategies including prevention or early detection of disease, improved health maintenance, and development of tailored therapy for patients with rare genetic diseases.
Biallelic Mutations in BRCA1 Cause a New Fanconi Anemia Subtype
01/08/2015

The proband presented at birth with microsomia and dysmorphic features (Fig. 1A). Growth parameters were less than the 0.4 percentile at term (birth weight 1990g, height 40.5 cm, head circumference (HC) 27 cm), and subsequent catch-up growth was not evident at 25 years of age (weight 40 kg, −3.03 S.D.; 135 cm tall, −4.35 S.D.; HC 48.5 cm, approx.−4 to −5 S.D.). Additional congenital abnormalities included sparse hair, upslanted palpebral fissures, blepharophimosis, a narrow palate, dental malocclusion, a high-pitched and hoarse voice, hyper and hypopigmented skin lesions, duodenal stenosis and a slightly enlarged left kidney. She has proximally inserted thumbs (Fig. 1A), 2nd digit camptodactyly, 2–3 toe syndactyly and hyperextensible knees as well as a history of hip dislocation. Conductive hearing loss was diagnosed at 4 years of age. Bone age at 2y 3m was delayed (1y and 6m (−2S.D.)), but had normalized by 9 years. The patient also has mild intellectual disability with significantly delayed speech. At 23 years of age she was diagnosed with ductal breast carcinoma that was estrogen and progesterone receptor positive and Her2 negative. Mastectomy was performed followed by treatment with docetaxel, fluorouracil-epirubicin-cyclophosphamide and radiation therapy. A prophylactic mastectomy was performed on the contralateral breast at age 25. The patient did not experience unusual treatment associated toxicity and has not been diagnosed with bone marrow failure to date.
Evidence for Clinical, Genetic and Biochemical Variability in Spinal Muscular Atrophy With Progressive Myoclonic Epilepsy
01/12/2014

The results of the WES and the functional studies prompted an electromyography (EMG) study that showed evidence of motor neuron disease despite only mild proximal muscle weakness.
Mutations in PIK3R1 Cause SHORT Syndrome
06/06/2013

Our findings show that PIK3R1 mutations are the major cause of SHORT syndrome and suggest that the molecular mechanism of disease might involve downregulation of the PI3K-AKT-mTOR pathway.
Targeted therapies for congenital myasthenic syndromes: systematic review and steps towards a treatabolome

We assess the strength and quality of the evidence and create a dataset that provides the foundation for a computer-aided system to enable clinicians to gain easier access to information about treatable variants and the evidence they need to consider.