With dominant inheritance one parent has a single faulty dominant gene and a normal gene. This dominant gene overpowers the effects of the normal gene and results in the affected individual displaying signs and symptoms of the disease. Each child of an affected parent can be either affected or not affected. To be an affected child, the child must inherit the single faulty dominant gene from the affected parent. Each child of an affected parent has a 50% chance of inheriting the dominant form of EB; and a 50 % chance of being unaffected.

With recessive inheritance both parents carry a normal gene, and a faulty, recessive gene. The parents, although carriers, are unaffected by the faulty gene and do not display any signs or symptoms of the disease. Each child of an affected parent can be either affected, not affected, or a carrier. To be an affected child, the child must inherit a defective copy of the EB gene - one from each parent - to have EB. Each time two carrier parents conceive a child, there is a 25% chance that the child will have a recessive form of EB; there is a 50% chance that a child will be a carrier; and a 25% chance that the child will be unaffected.

The Three Major Categories of EB

Epidermolysis Bullosa Simplex (EBS)

The most common form of EBS is the mild subtype Weber - Cockayne. It is characterised by occasional blistering primarily affecting the feet and hands. The nails, mucous membranes (includes the digestive tract and mouth) and teeth are unaffected. The more severe forms are the Dowling -Meara and Koebner subtypes. These forms are characterised by generalised blistering with involvement of the nails, teeth, or mucous membranes. EBS is also often referred to as the non-scarring type.

EBS - Weber Cockayne

Junctional Epidermolysis Bullosa (JEB)

The most severe type of JEB is the Herlitz or gravis variant and is associated with generalised blistering at birth, significant mucous membrane involvement, early loss of nails and pitted teeth with underdeveloped enamel. The survival rate is very low with the Herlitz variant with patients often succumbing to the disorder within the first two years of life. The non-Herlitz variant is a less severe form of the Herlitz variant and generally carries a better prognosis.

Herlitz JEB

Dystrophic Epidermolysis Bullosa (DEB)

DEB is characterised by extensive blistering of the skin that heals with scarring. Patients with dominantly inherited DEB in general show more localised and/or less severe disease than recessive patients. Sometimes the mucous membranes (includes the digestive tract and mouth) are involved. Patients with recessively inherited DEB can present with a mild, localised form of the disease however, most cases are characterised by extensive blistering and scarring. Often, the scarring process can lead to contractures of the limbs or mitten-hand deformities of the hands. In addition, often the mucous membranes are involved. Perhaps the most severe and devastating complication of recessive DEB is the development of squamous cell carcinomas in the areas of chronic blistering and scarring.

Dominant DEB	Dominant DEB
Recessive DEB

What causes EB?

A genetic change ormutation in one of the genesassociated with Epidermolysis Bullosa (EB) results in the skin layers not adhering properly to each other causing areas of structural weakness. As a result, the fragile skin is vulnerable to damage from mild friction, causing the blisters, which are the characteristic feature of EB.

Diagnosis of EB

Diagnosis of EB is first dependant on the patient's clinical presentation and family history. Information from electron microscopy and immunofluorescence mapping from a skin biopsy is often required to assist in providing a diagnosis.

Electron microscopy involves the use of a highly powered microscope that evaluates the skin sample by looking at the level of skin separation present and also noting the number and appearance of specific structures, such as anchoring fibrils or hemidesmosomes, located within the skin. This will assist in diagnosing the correct subtype of EB.

Electron micrographs of the dermal-epidermal junction of skin samples obtained by a skin biopsy and found to be normal (A) and affected with JEB (B). The hemidesmosomes (arrows) are formed in normal skin and absent in the affected skin. Source: Dr Dédée Murrell, Consultant Dermatologist St George Hospital NSW.

Immunofluorescence mapping involves using the skin sample and a panel of antibodies tagged with a fluorescent marker to detect the presence, or degree of binding, of the antibodies to the skin protiens. This may provide an indication as to the specific protein involved in the structural weakness of the skin.

Immunofluorescance mapping of normal skin (A) and affected (B). Source: Dr Dédée Murrell, Consultant Dermatologist St George Hospital NSW.

Current Therapy of EB

Currently, there is no permanent treatment for EB. At present, treatment involves protecting the skin from injury and infection. Management of this disorder is usually under the care of a dermatologist but may include specialists such as a podiatrist, dentist and gastroenterologist.

Gene Therapy and EB

Within the realm of experimental medicine, gene therapy involves the transfer of a therapeutic or unaltered gene into specific cells of an individual in order to repair a genetic mistake. Presently, gene therapy is not available in the permanent treatment of EB however, important strides have been made. Dr. Peter Marinkovich, from Stanford University in California, successfully transferred a corrected gene to a JEB patient's keratinocytes/cells. He was able to demonstrate normal expression of the protein in the grafted skin on a mouse for up to 12 weeks (this is the longest time period for which they can maintain grafts on mice). This data verifies the effectiveness of a potential gene therapy approach and will assist in obtaining FDA approval for human trials.