Rare Genetic Skin Diseases

What is a rare (orphan) disease?

A disease is called 'rare' when it is found in only a small portion of the population. In Europe, a disease is classified as 'rare' if it affects fewer than 1 in 2,000 people. In the United States, a 'rare' disease is considered to occur in fewer than 200,000 people at any given time.

Although this may appear to be a very small number, there are currently between 5,000 and 7,000 distinct rare diseases and this number is expected to continuously rise. Orphan diseases can affect people of any age (many children), gender, or ethnicity and collectively millions of individuals worldwide have been diagnosed. In Europe, about 30 million people are affected, which is approximately 7% of the entire population.

Various causes may underlie these diseases, however, approximately 80% of them are of genetic origin. Since diagnosis and treatment of most rare diseases are complex and challenging, they can have a significant impact on the lives of individuals and their families.

What is a genetic disease?

Genetic diseases arise from irregularities or abnormalities in a person's DNA. DNA (or deoxyribonucleic acid) is the genetic material that carries the instructions for the growth and function of all living organisms, including humans. A change (=mutation) in the DNA can disturb normal functioning and development of bodily structures, leading to a genetic disorder. Some may be considered mild with little impact on an individual's health, whereas others may be severe and life-threatening.

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 the complete set of genetic instructions encoded in the DNA of a human cell. It is located in the nucleus of every body cell, organized into 23 pairs of chromosomes, with one pair determining the sex (XX in females, XY in males). Mature egg and sperm cells carry only one element of each chromosome pair, which combines during fertilization. Each chromosome contains thousands of genes (sequence of monomeric untis in the DNA, the nucleotides). The information contained in a gene is used to make proteins, large biomolecules that perform many relevant functions within organisms and providing structure to cells. Proteins are made up of amino acids, and the sequence of amino acids in a protein is determined by the sequence of nucleotides in a gene. It is currently estimated that there are 19,000 to 20,000 genes in the human genome, coding for proteins.

The human genome includes both coding and non-coding DNA regions (genes). The coding regions, which carry instructions for protein synthesis, represent a minor fraction, comprising less than 2% of the genome. The non-coding regions, which make up the majority of the genome, include regulatory elements that control the expression of genes, as well as other functional and structural elements.


Many types of genetic diseases exist, which can be broadly classified into several categories:

  1. Single-gene disorders: are caused by mutations in one gene that cna be identified through specific analyses available at a limited number of laboratories. Examples: epidermolysis bullosa, ichtyosis, neurofibromatosis, cystic fibrosis, Huntington's disease

  2. Chromosomal disorders: are caused by changes in the number or structure of chromosomes and can be detected through cytogenetic tests (e.g. karyotype) Examples: Down syndrome, Turner syndrome

  3. Complex disorders: are caused by a combination of genetic and environmental factors and can be influenced by multiple genes. Examples: atopic dermatitis, psoriasis, heart disease, diabetes​​​

  4. Mitochondrial disorders: are caused by mutations in the mitochondrial DNA and may induce a wide range of symptoms including muscle weakness, vision loss, cognitive impairment. Examples: Mitochondrial myopathy, Leigh syndrome

What is a rare genetic disease of the skin?

Genetic skin diseases, or genodermatoses, are inherited conditions that primarily affect the skin and its appendages. 

These disorders are typically caused by single gene mutations that can be passed down from one or both carrier parents, or may arise spontaneously during the maturation of parents' egg or sperm cell. This group of disorders is very heterogenous and comprises more than 400 distinct clinical entities, almost all rare.

Genodermatoses frequently manifest at birth or early in life, are typically chronic, often severe and can be life-threatening. Thus, genodermatoses have significnat medical and social implications. Diagnosis can be challenging, as healthcare professionals may not be familiar with their clinical presentation and diagnostic tests are only available in a few specialized laboratories. Furthermore, the lack of curative treatments presents significant challenges in the clinical management of these patients, often requiring a costly and time-consuming multidisciplinary approach. Finally, both patients and their families may experience a significant reduction in their quality of life due to the negative psycho-social effects of the diseases' physical manifestations and the loss of autonomy/independence.

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

The diagnosis and treatment of genetic diseases can be complex, and may require genetic testing, counseling and specialized medical care. Although many genetic diseases cannot be cured, there are treatments and therapies available to manage symptoms and improve quality of life. Advances in scientific research are crucial to improve diagnosis and management of rare genetic skin diseases. The advent of new molecular biology technologies have enabled the identification of an increasing number of genes responsible for genodermatoses. Thus, molecular and pre-natal diagnosis is now available for the majority of these diseases.

However, in many cases, the connection between the mutated gene and disease manifestation is still unknown, which has hindered the development of therapeutic approaches. In the absence of curative therapies, the management of these disorders focuses on early diagnosis, preventing complications and improving patients’ quality of life.

A relevant challenge is that only a few European centrers are equipped to handle these diseases and even their expertise is limited to a few disorders. Expert knowledge in diagnosis, management and research initiatives are isolated and scattered throughout Europe. As a result, patients often struggle to find healthcare teams with the necessary expertise in highly specialised and multidisciplinary management. A Europe-wide mobilization of activities and resources is necessary to facilitate the development of cost-effective health care services that substantially improve patient outcomes.

The GENESKIN project has made significant strides in this direction, actively promoting collaboration between European expert groups in the field of genetic skin diseases. The GENESKIN website, launched during the project and now managed by the EDF, provides up-to-date information on genetic skin diseases, with a particular focus on providing patients with 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 European Union has made the fight against rare disease a priority, with the adoption of a Recommendation in 2009 (2009/C151/02) demanding that Member States develop a plan for guiding relevant actions in this field. To support this effort, the European Commission established the European Union Committee of Experts on Rare Diseases (EUCERD) (2009/872/EC), which includes representatives of Member States and stakeholders in the field. 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 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.

This includes promoting action on rare diseases, where community action can provide added value to national efforts. The program has funded more than 30 projects on rare diseases to date, including the well-known European website Orphanet.

Research on rare diseases is also an objective of the Framework Programmes for Research and Technological Development, which seek to improve the prevention and management of major causes of mortality and ill health. The 7th Framework Programme (2007-2013) focuses on pan-European studies of natural history, pathophysiology and the development of preventive, diagnostic and therapeutic interventions for rare diseases.

International collaboration is also seen as essential, leading to the launch of the​​​​​​​ International Rare Diseases Research Consortium (IRDiRC) in 2011, with the aim of  delivering 200 new therapies and diagnostic tools for most rare diseases by 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
  • 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 an integral part of EDF's objectives. 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 communication among dermatologists, other specialists involved in genetic skin disease care, patients’ organizations, pharmaceuticals and biotechnology companies, healthcare providers and general public.

The ultimate goal is to contribute to the improved care and quality of life of affected patients and their families.