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 are 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 is working in this direction, actively supporting the cooperation between European expert groups in the field of genetic skin diseases. In particular for patients, the program 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, as stated in both the Community Action Programmes for Public Health and in the Framework Programmes for Research and Technological Development.
One of the three general objectives of the present Community Action Programme for Public Health (2003-2008) is to collect  information through initiatives such as networks, training and the dissemination of data and knowledge. A second objective is the rapid response to health threats through the development of prevention strategies and mechanisms, and the exchange of expertise on non-communicable disease threats, including rare diseases. Within this Community Action Programme, eight projects 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 general 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. It is also an objective of specific topics defined by these Programmes. Under the 5th Framework Programme, 47 projects on rare diseases were funded. In the present 6th Framework Programme (2002-2006), the Thematic Priority “Life Sciences, Genomics and Biotechnology for Health” includes a specific topic on combating rare diseases.