Rare versus common diseases: a false dichotomy in precision medicine

Abstract

Precision medicine initiatives are being launched worldwide, each with the capacity to sequence many thousands to millions of human genomes. At the strategic planning level, all are debating the extent to which these resources will be directed towards rare diseases (and cancers) versus common diseases. However, these are not mutually exclusive choices. The organizational and governmental infrastructure created for rare diseases is extensible to common diseases. As we will explain, the underlying technology can also be used to identify drug targets for common diseases with a strategy focused on naturally occurring human knockouts. This flips on its head the prevailing modus operandi of studying people with diseases of interest, shifting the onus to defining traits worth emulating by pharmaceuticals, and searching phenotypically for people with these traits. This also shifts the question of what is rare or common from the many underlying causes to the possibility of a common final pathway.

Fig. 1. Five different epilepsies, five different treatments.

Worldwide, ~50 million people have epilepsy, making it one of the most common neurological diseases. Pediatric‐onset intractable cases are defined by onset before 18-years-of-age with two failed trials of tolerated appropriately-chosen-and-used anti-epileptic drugs (AED) to achieve sustained seizure freedom. An estimated 30% of epilepsy patients fall into this category. Diverse disease etiologies make accurate and specific diagnoses challenging. From the ClinGen Epilepsy Gene Curation Expert Panel, there are 2702 genes associated with epilepsy. A proper molecular diagnosis is therefore essential. Here, we show five examples from the University of Hong Kong (HKU) Paediatric Exome Project, demonstrating how genome medicine enables personalized treatment of difficult epilepsy cases. Informed consent was obtained from the parents for the use of these clinical photographs.

Fig. 2. Summary of disease prevalence from Orphanet.

Data are sorted from most to least common disease. The solid red line is the cumulant.