Genodermatoses are genetic diseases that are expressed as skin conditions. The diseases are usually detectable upon birth if not soon after. The type of disease depends on how the genes are affected but the resultant conditions can be serious, rare and severely affect the patient’s life by leading to disabilities, a short life span, and the development of other chronic diseases and cancer.
Patient suffering from neurofibromatosis
There are approximately 400 different kinds of genodermatoses with an incidence that can vary from between 1 in 6000 people to 1 in 500,000 people. The burden of the disease can be difficult for the patient and families who potentially have access to only a very limited range of expensive medicines to help in disease management. They can also find it challenging to have normal lives at school, work or socially.
Single gene disorders (monogenic)
There are approximately 170 skin disorders that are caused by an abnormality in a single gene. The way a patient is affected can depend on environmental factors.
When there is autosomal dominant inheritance, both men and women can develop the disease. One of their parents will usually have been affected. Examples of diseases include:
- Acute intermittent porphyrin
This shows blister symptoms most commonly in the late teens to early forties. It is also more common in women than men.
This causes blisters on the skin with rubbing or any type of friction. The skin can resemble that of burns patients. Approximately 1 in every 17,000 children born in the UK develop this condition.
The skin becomes rough, scaly and severely dry. The regeneration of the skin can either be too fast or too slow, resulting in the fish-like appearance of the skin.
In autosomal recessive (AR) inheritance approximately 1 in every 4 children from parents heterozygous for an abnormal gene can develop a genodermatosis. Both males and females can be affected though there may be no obvious family history of the disease. These types of diseases can be observed when the two parents come from the same ancestor. Examples of the disease include:
- Epidermolysis bullosa
- Acrodermatitis enteropathica
This can cause a rash around the mouth and also the anus alongside other symptoms.
In X-linked recessive inheritance, women can be a carrier and males are more likely to develop the diseases. It cannot be genetically transmitted from fathers to sons. Examples of this type of disease include:
This causes red spots on the skin due to globotriaosylceramide building up in body cells. The patient is also unable to sweat normally.
- Anhidrotic ectodermal dysplasia
The affected skin becomes more thin, scaly, wrinkled and darker. The patient also presents with areas in the skin without hair and can develop abnormally sparse hair growth (hypotrichosis).
For X-linked dominant diseases, affected males transmit the disease to their sons and affected females transmit the disease to half of their sons and half of their daughters. One example of a disease is:
In this condition, the patient first develops blisters. These later develop into warts on the skin. There can also be brown and grey skin discoloration.
In polygenic disorders, several gene mutations (defects) influence the type of disease that the patient experiences. As well as the interaction between these genes, the environment, race, the immune system, lifestyle and other factors have an impact on the phenotype of the disease. There are more than 100 types of these skin disorders. Some are as follows:
In this disease, white patches which lack melanin present on the skin of the patient. The disease can make it easier for the person’s skin to burn in the sun.
Hand of patient with vitiligo
The affected skin becomes flaky. Itchy and sore in areas such as the scalp, elbows, knees and lower back. The patients develop the condition because of a disorder in about 25 different genes that have been linked to its development when it presents genetically.
Patient with psoriasis on elbow
In this condition, blisters develop on the skin of the patients in areas such as the mouth, throat, genitals and nose.
Reviewed by Afsaneh Khetrapal BSc (Hons)
- Genodermatoses and rare skin disorders: http://www.genodermatoses-network.org/spip.php?article35
- US National Library of Medicine National Institutes of Health on Genodermatoses for practitioners – principles and concepts: http://www.ncbi.nlm.nih.gov/pubmed/20806176
- WO2009091889 A1 patent, Treatment of skin disorders with egfr inhibitors: http://www.google.com/patents/WO2009091889A1?cl=en
- Assistant Professor Dr. Khudair Kh. Al-Kayalli from the College of Medicine at Diyala University on genodermatoses/dermatology: http://www.medicine.uodiyala.edu.iq/uploads/lectures/dermatology/Genodermatosis.pdf
- NHS Choices on epidermolysis bullosa: http://www.nhs.uk/conditions/Epidermolysis-Bullosa/Pages/Introduction.aspx
- DermNet Nz on acrodermatitis enteropathica: http://www.dermnetnz.org/systemic/acrodermatitis-enteropathica.html
- NHS Choices on pemphigus vulgaris: http://www.nhs.uk/conditions/Pemphigus-vulgaris/Pages/Definition.aspx
- NHS Choices on psoriasis: http://www.nhs.uk/conditions/Psoriasis/Pages/Introduction.aspx
- Genetics Home Reference on anhidrotic ectodermal dsiplasia: https://ghr.nlm.nih.gov/condition/anhidrotic-ectodermal-dysplasia-with-immune-deficiency
- Genetics Home Reference on incontinentia pigmenti: https://ghr.nlm.nih.gov/condition/incontinentia-pigmenti
- Genetics Home Reference on Fabry disease: https://ghr.nlm.nih.gov/condition/fabry-disease
Porphyria Foundation on AIP: http://www.porphyriafoundation.com/about-porphyria/types-of-porphyria/AIP