Over 30 different subtypes of EB have now been described. Thanks to medical research over the last few decades we now know much more about the underlying causes. Skin consists of a tough protective outer layer known as the epidermis, an underlying dermis, where the blood vessels and nerves reside and a basement membrane in between. There are a number of different genes that, when faulty, can cause EB but all are responsible for making proteins that play a role in the area of the basement membrane. These proteins are responsible for the structure of the skin and for ‘gluing’ the epidermis and dermis to each other. Broadly, EB can be divided into three major types:
EB Simplex
EB simplex (EBS) is caused by mutations (or faults in the DNA) in the keratin 5 and keratin 14 genes and is almost always inherited in a dominant fashion. These keratin genes are responsible for making proteins that are involved in maintaining the structure of the upper layer of skin, above the basement membrane. In milder forms of EBS, the blistering tends to be mainly limited to the palms of the hands and soles of the feet, although friction can cause blistering elsewhere. There are however, more severe forms of EBS, such as the Dowling-Meara form, where blistering can be widespread and internal tissues, such as the oesophagus and intestines, may be affected.
Junctional EB
Junctional EB (JEB) is divided into two major subtypes, both of which are inherited in a recessive manner; Herlitz and non-Hertlitz JEB. The Herlitz variant is a very severe form of EB and is often associated with infant mortality. It is caused by changes in the COL17A1 which makes the collagen 17 protein or by changes in the genes LAMA3, LAMB3 and LAMC2, all of which are responsible for making parts of the laminin-32 protein. The non-Herlitz form is also caused by mutations in the LAMA3, LAMB3 and LAMC2 genes. There is also a rare and very severe form of JEB known as JEB with pylorus atresia, (caused by problems in the α6β4 integrin gene) which is additionally complicated by a blockage between the stomach and intestines and is often fatal in the first few months of life. All JEB proteins are involved in maintaining the structure of the skin through the basement membrane. In addition to skin problems, patients with JEB may suffer from problems with the eyes, teeth, nails, internal tissues and may experience hair loss.
Dystrophic EB
Dystrophic EB (DEB) can be either dominant or recessive but all forms are caused by mutations in the collagen 7A1 gene. The collagen 7 protein is a major part of what are known as anchoring fibrils, which are responsible for attaching the dermis and epidermis to each other. As the skin defects in this form of EB are deeper (below the basement membrane) than in the other forms, DEB is often associated with scarring. Recessive DEB is usually (but not always) very severe with internal linings affected, reduced flexibility of the joints, fusion of the fingers and toes and problems with the teeth, nails and eyes. It is also additionally complicated by the high risk of an aggressive form of skin cancer from early adulthood. In general the dominant form of DEB tends to be considerably milder, with a very low risk of skin cancer, although blistering may be widespread.
