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Epidermolysis bullosa dystrophica

MedGen UID:
37179
Concept ID:
C0079294
Disease or Syndrome
Synonyms: Dystrophic epidermolysis bullosa; Dystrophic epidermolysis bullosa, Hallopeau-Siemens type (formerly)
SNOMED CT: Dystrophic epidermolysis bullosa (254185007); DEB - Dystrophic epidermolysis bullosa (254185007); Epidermolysis bullosa dystrophica (254185007)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): COL7A1 (3p21.31)
 
Monarch Initiative: MONDO:0006543
Orphanet: ORPHA303

Disease characteristics

Excerpted from the GeneReview: Dystrophic Epidermolysis Bullosa
Dystrophic epidermolysis bullosa (DEB) is a genetic skin disorder affecting skin and nails that usually presents at birth. DEB is divided into two major types depending on inheritance pattern: recessive dystrophic epidermolysis bullosa (RDEB) and dominant dystrophic epidermolysis bullosa (DDEB). Each type is further divided into multiple clinical subtypes. Absence of a known family history of DEB does not preclude the diagnosis. Clinical findings in severe generalized RDEB include skin fragility manifest by blistering with minimal trauma that heals with milia and scarring. Blistering and erosions affecting the whole body may be present in the neonatal period. Oral involvement may lead to mouth blistering, fusion of the tongue to the floor of the mouth, and progressive diminution of the size of the oral cavity. Esophageal erosions can lead to webs and strictures that can cause severe dysphagia. Consequently, malnutrition and vitamin and mineral deficiency may lead to growth restriction in young children. Corneal erosions can lead to scarring and loss of vision. Blistering of the hands and feet followed by scarring fuses the digits into "mitten" hands and feet, with contractures and pseudosyndactyly. The lifetime risk of aggressive squamous cell carcinoma is higher than 90%. In contrast, the blistering in the less severe forms of RDEB may be localized to hands, feet, knees, and elbows with or without involvement of flexural areas and the trunk, and without the mutilating scarring seen in severe generalized RDEB. In DDEB, blistering is often mild and limited to hands, feet, knees, and elbows, but nonetheless heals with scarring. Dystrophic nails, especially toenails, are common and may be the only manifestation of DDEB. [from GeneReviews]
Authors:
Ellen G Pfendner  |  Anne W Lucky   view full author information

Additional description

From MedlinePlus Genetics
Dystrophic epidermolysis bullosa is one of the major forms of a group of conditions called epidermolysis bullosa. Epidermolysis bullosa cause the skin to be very fragile and to blister easily. Blisters and skin erosions form in response to minor injury or friction, such as rubbing or scratching. The signs and symptoms of dystrophic epidermolysis bullosa vary widely among affected individuals. In mild cases, blistering may primarily affect the hands, feet, knees, and elbows. Severe cases of this condition involve widespread blistering that can lead to vision loss, scarring, and other serious medical problems.

Researchers classify dystrophic epidermolysis bullosa into major types based on the inheritance pattern and features of the condition. Although the types differ in severity, their features overlap significantly and they are caused by mutations in the same gene.

Recessive dystrophic epidermolysis bullosa severe generalized (RDEB-sev gen) is the classic form of the condition and is the most severe. Affected infants are typically born with widespread blistering and areas of missing skin, often caused by trauma that occurs during birth. Most often, blisters are present over the whole body and affect mucous membranes such as the moist lining of the mouth and digestive tract. As the blisters heal, they result in severe scarring. Scarring in the mouth and esophagus can make it difficult to chew and swallow food, leading to chronic malnutrition and slow growth. Additional complications of ongoing scarring can include fusion of the skin between the fingers and toes, loss of fingernails and toenails, joint deformities (contractures) that restrict movement, and eye inflammation leading to vision loss. Additionally, people with RDEB-sev gen have a very high risk of developing a form of skin cancer called squamous cell carcinoma in young adulthood. In these individuals, the cancer tends to be unusually aggressive and is often life-threatening.

Other types of recessive dystrophic epidermolysis bullosa fall along a spectrum referred to as RDEB-generalized and localized (RDEB-gen and -loc). These forms of the condition are somewhat less severe than RDEB-sev gen and are distinguished by the affected regions of the body. Blistering is often limited to the hands, feet, knees, and elbows in mild cases, but may be widespread in more severe cases. Rare forms affect specific regions of the body, such as the shins or the abdomen. Affected people often have malformed fingernails and toenails. The RDEB-gen and -loc types involve scarring in the areas where blisters occur, but these forms of the condition do not cause the severe scarring characteristic of RDEB-sev gen.

Another major type of this condition is known as dominant dystrophic epidermolysis bullosa (DDEB). The signs and symptoms of this condition tend to be milder than those of the recessive forms, with blistering often limited to the hands, feet, knees, and elbows. The blisters heal with scarring, but it is less severe than in recessive forms of this condition. Most affected people have malformed fingernails and toenails, and the nails may be lost over time. In the mildest cases, abnormal nails are the only sign of the condition.  https://medlineplus.gov/genetics/condition/dystrophic-epidermolysis-bullosa

Professional guidelines

PubMed

Will LM, Reichrath J, Vogt T
J Dtsch Dermatol Ges 2021 Jul;19(7):983-986. Epub 2021 May 5 doi: 10.1111/ddg.14446. PMID: 33951274
Anton-Lamprecht I
J Invest Dermatol 1983 Jul;81(1 Suppl):149s-56s. doi: 10.1111/1523-1747.ep12540961. PMID: 6345689

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