Another extensive area where the principles of precision medicine are applied is in the field of rare and ultra-rare diseases. Rare Diseases (RD) are clinically heterogeneous, predominantly inherited, multisystem diseases with a very low prevalence in the general population, which affect the quality of life and social integration of patients or threaten their lives. In the European Union, a disease is defined as rare if it affects fewer than one patient per 2000 individuals; ultra-rare diseases are a subset of rare diseases with a prevalence of 1 per 200,000 populations. The severity of RDs lies in the fact that there are more than 8,000 different RDs (6,000 of which are genetically determined), so the cumulative number of patients is not negligible. It is estimated that RDs affect 1 in 16 individuals in the general population despite the low prevalence of individual clinical entities. Within the EU, a total of 24 European Reference Networks for Rare Diseases (ERNs) have therefore been established for patients with rare diseases. At the University Hospital Brno, we have a total of 5 ERN centers (ERN-EpiCare, ERN-EuroBloodNet, ERN-EURO-NMD, ERN PaedCan, and ERN Skin). The centers within these networks provide cutting-edge multidisciplinary care for patients with a specific type of diagnosed rare disease.
As more than 80% of rare diseases have a genetic origin, obtaining an accurate molecular diagnosis is crucial for appropriate clinical care, family and reproductive counseling, and support. However, diagnosing these diseases can be challenging due to the limited number of patients (often very small number or low tens of patients worldwide) and the lack of information and clinical experiences. For undiagnosed pediatric patients (more information) and their families, it is challenging to face sometimes lengthy and complex diagnostic procedures that can take several years, sometimes referred to as a "diagnostic odyssey." The aim of precision medicine in this field is to find and describe the genetic basis of the disease, thus enabling not only a diagnosis but also a better understanding of the individual clinical manifestations of the patient and, if the nature of the disease allows it, to set up an appropriate treatment plan or long-term follow-up plan.
A specific group of rare diseases where the principles of precision medicine have been successfully implemented in recent years is vascular malformations (more information). The causes of vascular malformations are genetic mutations in signaling pathways responsible for the formation and development of blood vessels, which are very well known and can be therapeutically influenced by targeted oncology drugs. After appropriate molecular testing, it is thus possible to treat these diseases in a personalized way.