Epidermolysis bullosa dystrophica
Encyclopedia
Epidermolysis bullosa dystrophica or Dystrophic EB (DEB) is an inherited disease affecting the skin and other organs. "Butterfly children" is the term given to those born with the disease, as their skin is seen to be as delicate and fragile as that of a butterfly.
s) within the human COL7A1 gene encoding the protein
type VII collagen (collagen VII). DEB-causing mutations can be either dominant or recessive.
Most families with family members with this condition have distinct mutations.
Collagen VII is a very large molecule (780 nm) that dimerizes to form a semicircular looping structure: the anchoring fibril. Anchoring fibrils are thought to form a structural link between the epidermal basement membrane
and the fibrillar collagen
s in the upper dermis
.
Types include:
ing.
Collagen VII is also associated with the epithelium
of the esophageal lining
, and DEB patients may suffer from chronic scarring, webbing, and obstruction of the esophagus
. Affected individuals are often severely malnourished due to trauma to the oral and esophageal mucosa and require feeding tubes for nutrition. They also suffer from iron-deficiency anemia of uncertain origin, which leads to chronic fatigue.
Open wounds on the skin heal slowly or not at all, often scarring extensively, and are particularly susceptible to infection. Many individuals bathe in a bleach and water mixture to fight off these infections.
The chronic inflammation leads to errors in the DNA of the affected skin cells, which in turn causes squamous cell carcinoma
(SCC). The majority of these patients die before the age of 30, either of SCC or complications related to DEB.
response against type VII collagen can result in an acquired form of epidermolysis bullosa called epidermolysis bullosa acquisita.
There exist other types of inherited epidermolysis bullosa
, junctional epidermolysis bullosa and epidermolysis bullosa simplex, which are not related to type VII collagen deficiency. These arise from mutations in the genes encoding other proteins of the epidermis or the basement membrane
at the junction between the epidermis and the dermis
.
Causes
DEB is caused by genetic defects (or mutationMutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s) within the human COL7A1 gene encoding the protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
type VII collagen (collagen VII). DEB-causing mutations can be either dominant or recessive.
Most families with family members with this condition have distinct mutations.
Collagen VII is a very large molecule (780 nm) that dimerizes to form a semicircular looping structure: the anchoring fibril. Anchoring fibrils are thought to form a structural link between the epidermal basement membrane
Basement membrane
The basement membrane is a thin sheet of fibers that underlies the epithelium, which lines the cavities and surfaces of organs including skin, or the endothelium, which lines the interior surface of blood vessels.- Composition :...
and the fibrillar collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
s in the upper dermis
Dermis
The dermis is a layer of skin between the epidermis and subcutaneous tissues, and is composed of two layers, the papillary and reticular dermis...
.
Types include:
| OMIM | Name | Locus | Gene |
|---|---|---|---|
Presentation and prognosis
The deficiency in anchoring fibrils impairs the adherence between the epidermis and the underlying dermis. The skin of DEB patients is thus highly susceptible to severe blisterBlister
A blister is a small pocket of fluid within the upper layers of the skin, typically caused by forceful rubbing , burning, freezing, chemical exposure or infection. Most blisters are filled with a clear fluid called serum or plasma...
ing.
Collagen VII is also associated with the epithelium
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
of the esophageal lining
Esophagus
The esophagus is an organ in vertebrates which consists of a muscular tube through which food passes from the pharynx to the stomach. During swallowing, food passes from the mouth through the pharynx into the esophagus and travels via peristalsis to the stomach...
, and DEB patients may suffer from chronic scarring, webbing, and obstruction of the esophagus
Esophagus
The esophagus is an organ in vertebrates which consists of a muscular tube through which food passes from the pharynx to the stomach. During swallowing, food passes from the mouth through the pharynx into the esophagus and travels via peristalsis to the stomach...
. Affected individuals are often severely malnourished due to trauma to the oral and esophageal mucosa and require feeding tubes for nutrition. They also suffer from iron-deficiency anemia of uncertain origin, which leads to chronic fatigue.
Open wounds on the skin heal slowly or not at all, often scarring extensively, and are particularly susceptible to infection. Many individuals bathe in a bleach and water mixture to fight off these infections.
The chronic inflammation leads to errors in the DNA of the affected skin cells, which in turn causes squamous cell carcinoma
Squamous cell carcinoma
Squamous cell carcinoma , occasionally rendered as "squamous-cell carcinoma", is a histologically distinct form of cancer. It arises from the uncontrolled multiplication of malignant cells deriving from epithelium, or showing particular cytological or tissue architectural characteristics of...
(SCC). The majority of these patients die before the age of 30, either of SCC or complications related to DEB.
Related conditions
In the absence of mutations of the COL7A1 gene, an autoimmuneAutoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
response against type VII collagen can result in an acquired form of epidermolysis bullosa called epidermolysis bullosa acquisita.
There exist other types of inherited epidermolysis bullosa
Epidermolysis bullosa
Epidermolysis bullosa is an inherited connective tissue disease causing blisters in the skin and mucosal membranes, with an incidence of 1/50,000. Its severity ranges from mild to lethal. It is caused by a mutation in the keratin or collagen gene....
, junctional epidermolysis bullosa and epidermolysis bullosa simplex, which are not related to type VII collagen deficiency. These arise from mutations in the genes encoding other proteins of the epidermis or the basement membrane
Basement membrane
The basement membrane is a thin sheet of fibers that underlies the epithelium, which lines the cavities and surfaces of organs including skin, or the endothelium, which lines the interior surface of blood vessels.- Composition :...
at the junction between the epidermis and the dermis
Dermis
The dermis is a layer of skin between the epidermis and subcutaneous tissues, and is composed of two layers, the papillary and reticular dermis...
.