What is a rare disease?

A disease is defined as “rare” if it occurs in only a small number of people compared to the general population. According to the present European regulation, a disease is classified as “rare” if it affects less than 1 in 2,000 people. Although this figure seems to be very low, between 5,000 and 7,000 distinct rare diseases have so far been described, and this number is expected to increase further. In Europe, some 30 million people are affected by rare diseases, i.e. approximately 7% of the entire population. While the range of causes of rare diseases is wide, most (approximately 80%) have identified genetic origin.


What is a genetic disease?

With the exception of traumatic injuries, almost all human diseases present genetic factors contributing to their aetiology or pathogenesis. However, a disease is considered “genetic” when it result from heritable alterations of the genome in the affected individual. The human genome is mostly encased within the nucleus of every cell of the body and is organized in 23 pairs of chromosomes, one of which specifies the sex (XX in women, XY in men). Mature egg and sperm cells carry only one element of each pair allowing the chromosome pairs to form again by fertilization. Each chromosome presents thousands of genes, which constitute the units of heredity. Genes (the total number in humans is estimated at approximately 28,000) consist of DNA, the molecule forming the blueprint of our physical existence.
Genetic diseases can arise from two kinds of alterations to the genetic heritage, chromosome changes and single gene changes. While chromosomal abnormalities are detected by cytogenetic tests (e.g. karyotype), gene mutations are identified by specific analyses available in a limited number of laboratories.

What is a rare genetic disease of the skin?

Genetic skin diseases, or genodermatoses, are heritable conditions mainly affecting the skin and its appendages. They are typically caused by single gene mutations which may be transmitted by one or both carrier parents, or arise as new events during the maturation of sperm or egg cells in healthy parents. This heterogeneous group of disorders comprises nearly 300 distinct clinical entities, almost all rare. They frequently occur at birth or early in life, are generally chronic, often severe and may even be life-threatening. Thus, genodermatoses have important medical and social implications. They are difficult to diagnose, as healthcare professionals may be not aware of their clinical presentation and diagnostic tests are available only in a few laboratories. Furthermore, the current absence of curative therapies poses significant problems in the clinical management of patients, which frequently requires a costly and time consuming multidisciplinary approach. Finally, the quality of life of both patients and their families may be severely compromised by the negative psycho-social impact of disease physical manifestations and the lack or loss of autonomy.

How to improve the diagnosis and management of rare genetic skin diseases?

Major advances in the diagnosis and management of rare genetic skin diseases can only ensue from scientific research. The advent of new technologies in molecular biology is facilitating the identification of an increasing number of genes responsible for genodermatoses. Molecular and pre-natal diagnosis is therefore now available for the majority, but not all, of these diseases. However, in many cases, the link between the mutated gene and the manifestation of the disease remains unknown. To date, this lack of knowledge has hampered the development of therapeutic approaches, while scientific research is trying to make up the short-fall.
In the absence of curative therapies, the management of these disorders is at present focused on early diagnosis, preventing complications and improving patients’ quality of life. A significant logistical problem is that only a few centres in Europe are able to deal with these diseases and even their expertise is, in general, limited to a few disorders. Thus, expert knowledge in diagnosis, management and research initiatives are isolated and scattered throughout Europe. As a result, patients experience significant difficulties in finding expert healthcare teams able to offer highly specialised and multi-disciplinary management. This situation can only be overcome by a Europe-wide mobilisation of activities and resources to facilitate the development of substantially improved and cost-effective health care services.
The GENESKIN project has worked in this direction, actively supporting the cooperation between European expert groups in the field of genetic skin diseases. The GENESKIN website, started during the GENESKIN project and now managed by the EDF, aims to provide updated information on genetic skin diseases. In particular for patients, the website seeks to provide precise information on where and how to obtain appropriate treatment and early diagnosis of these conditions.

What is the European policy in the field of rare diseases?

The fight against rare diseases is a specific objective of European Union policy. In 2009 the European Council has adopted a Recommendation on an action in the field on rare diseases (2009/C151/02) demanding that Member States “elaborate and adopt a plan or a strategy as soon as possible, preferably by the end of 2013 at the latest, aimed at guiding and structuring relevant actions in the field of rare diseases, within the framework of their health and social systems”. The European Commission has then established a European Union Committee of Experts on Rare Diseases (EUCERD) (2009/872/EC), composed of representatives of all EU Member States and main stakeholders (pharmaceutical industry, patients’ organisations, public health and research projects funded by the European Commission, the relevant European authorities in the fields of research and public health). The EUCERD shall assist the European Commission with the preparation and implementation of Community activities in the field of rare diseases.
Strategies for tackling rare diseases are also a priority of both the Community Action Programmes for Public Health and the Framework Programmes for Research and Technological Development. The three main objectives of the Second Community Action Programme for Public Health (2008-2013) are: (i) to improve citizens' health security; (ii) to promote health, which involves reducing inequalities in this area; (iii) to generate and disseminate health information and knowledge. In particular, aim (ii) specifically mentions the promotion of action on rare diseases, where Community action by tackling their determinants can provide significant added value to national efforts. Within the first and second Community Action Programmes for public health, 32 projects on rare diseases have been funded to date, among which Orphanet is the best known European website dedicated to rare diseases and orphan drugs. Research on rare diseases is part of the objectives of the Framework Programmes for Research and Technological Development which seek to improve the prevention and management of important causes of mortality and ill health. Under the 5th and 6th Framework Programme, 47 and 59 projects on rare diseases were funded, respectively. In the 7th Framework Programme (2007-2013), rare disease research features under the theme “Health”, and the focus is on pan-European studies of natural history, pathophysiology, and the development of preventive, diagnostic and therapeutic interventions.
Finally, recognition of the need for strengthened international collaboration has led in 2011 to the launch of an International Rare Diseases Research Consortium (IRDiRC), with the European Commission and the US National Institutes of Health as the initiating institutions. IRDiRC will team up researchers and funding agencies with the ambitious objective to deliver 200 new therapies for rare diseases and diagnostic tools for most rare diseases by the year 2020.

Why and how is European Dermatology Forum involved in rare diseases?

Major aims of the European Dermatology Forum (EDF) are the improvement and dissemination of knowledge on skin diseases to stakeholders and society in general, and the promotion of the highest possible standards in their prevention, diagnosis and treatment. In this perspective, dissemination of knowledge on rare diseases, which represent a significant proportion of dermatological diseases, is integral part of EDF goals. By supporting the maintenance and development of the GENESKIN website, the EDF seeks (i) to increase awareness about rare genetic skin diseases at the European level, (ii) to facilitate contacts among dermatologists, and between dermatologists and other specialists involved genetic skin disease care, as well as between dermatologists and patients’ organizations, pharmaceuticals and biotechnology companies, healthcare providers and general public. The final goal is to contribute to improved care and quality of life of affected patients and their families.