A rare disease is a condition that affects fewer than one in 2000 people. It is often reported that there are approximately 7000 rare diseases, of which about 80% are genetic. This figure is an underestimate if you include cancers and infectious diseases.
It is not humanely possible for an individual doctor to attain knowledge and experience with anything more than a tiny fraction of all rare diseases. Therefore, an important cognitive step is suspecting that the patient might have a rare disease of some kind. The following memory aide can be used to raise suspicion whether a patient has a rare disease.
Family history: multiple affected siblings or individuals in multiple generations. Remember that lack of a family history does NOT rule out genetic causes.
G: group of congenital anomalies: Common anatomic variations are, well, common; but two or more anomalies are much more likely to indicate the presence of a syndrome with genetic implications.
E: extreme or exceptional presentation of common conditions: Early onset cardiovascular disease, cancer, or renal failure. Unusually severe reaction to infectious or metabolic stress. Recurrent miscarriage. Bilateral primary cancers in paired organs, multiple primary cancers of different tissues
N: neurodevelopmental delay or degeneration: Developmental delay in the paediatric age group carries a very high risk for genetic disorders. Developmental regression in children or early onset dementia in adults should similarly raise suspicion for genetic etiologies
E: extreme or exceptional pathology: Unusual tissue histology, such as pheochromoctyoma, acoustic neuroma, medullary thyroid cancer, multiple colon polyps, plexiform neurofibromas, multiple exostoses, most paediatric malignancies.
S: surprising laboratory values: Markedly abnormal pathology results
There are many sources to assist with the diagnostic process.
- Rare Disease 101 course: https://learn.m4rd.org/
- https://www.findzebra.com/: Open access, web-based tool specifically to assist rare disease diagnosis. Start with two most specific terms.
- http://www.omim.org/: The OMIM database is a comprehensive compendium of human genes and genetic phenotypes
- http://www.orpha.net/: Search keywords such as a disease or genes. tutorial
- https://compbio.charite.de/phenomizer/: An open access, web-based tool to assist diagnosis
- https://rarediseases.org/: NORD (national organisation for rare diseases)
- https://www.eurordis.org/: Rare Diseases Europe