Rare Diseases

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

Resources

• 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