| Epidermolysis bullosa dystrophica |
| Classification and external resources |
| Specialty |
medical genetics |
| ICD-10 |
Q81.2 |
| ICD-9-CM |
757.39 |
| OMIM |
131750 |
| DiseasesDB |
29580 |
| MeSH |
D016108 |
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.
Contents
- 1 Classification
- 2 Signs and symptoms
- 3 Causes
- 4 Pathophysiology
- 5 See also
- 6 References
- 7 External links
Classification
| Name |
Locus & Gene |
OMIM |
Dominant dystrophic epidermolysis bullosa (DDEB)
- Also known as "Cockayne-Touraine disease", this variant is characterized by vesicles and bullae on the extensor surfaces of the extremities.[1][2]
|
3p21.3 (COL7A1) |
131750 |
Recessive dystrophic epidermolysis bullosa (RDEB)
- Also known as "Hallopeau–Siemens variant of epidermolysis bullosa"[3] and "Hallopeau–Siemens disease",[4] this variant results from mutations in the gene encoding type VII collagen, COL7A1, characterized by debilitating oral lesions that produce pain, scarring, and microstomia.[5][2] It is named for François Henri Hallopeau and Hermann Werner Siemens.
|
11q22-q23 (COL7A1), 3p21.3 (MMP1) |
226600 |
| Epidermolysis bullosa dystrophica, pretibial |
3p21.3 (COL7A1) |
131850 |
| Epidermolysis bullosa pruriginosa |
3p21.3 (COL7A1) |
604129 |
| Epidermolysis bullosa with congenital localized absence of skin and deformity of nails |
3p21.3 (COL7A1) |
132000 |
| Transient bullous dermolysis of the newborn (TBDN) |
3p21.3 (COL7A1) |
131705 |
Signs and symptoms
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 blistering.
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.
Causes
DEB is caused by genetic defects (or mutations) within the human COL7A1 gene encoding the protein type VII collagen (collagen VII).[6] DEB-causing mutations can be either dominant or recessive.
Most families with family members with this condition have distinct mutations.[7]
Collagen VII is a very large molecule (300 kDa) 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 collagens in the upper dermis.
Pathophysiology
In the absence of mutations of the COL7A1 gene, an autoimmune response against type VII collagen can result in an acquired form of epidermolysis bullosa called epidermolysis bullosa acquisita.[8]
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.[9]
See also
References
- ^ James, Berger & Elston 2005, p. 558
- ^ a b Freedberg et al. 2003, p. 601
- ^ Freedberg et al. 2003
- ^ Rapini, Bolognia & Jorizzo 2007, p. 458
- ^ James, Berger & Elston 2005, pp. 558–9
- ^ Varki, R.; Sadowski, S.; Uitto, J.; Pfendner, E. (March 2007). "Epidermolysis bullosa. II. Type VII collagen mutations and phenotype–genotype correlations in the dystrophic subtypes". Journal of Medical Genetics 44 (3): 181–92. doi:10.1136/jmg.2006.045302. PMC 2598021. PMID 16971478.
- ^ Csikós, M.; Szőcs, H. I.; Lászik, A.; Mecklenbeck, S.; Horváth, A.; Kárpáti, S.; Bruckner-Tuderman, L. (May 2005). "High frequency of the 425A→G splice-site mutation and novel mutations of the COL7A1 gene in central Europe: significance for future mutation detection strategies in dystrophic epidermolysis bullosa". British Journal of Dermatology 152 (5): 879–886. doi:10.1111/j.1365-2133.2005.06542.x. PMID 15888141.
- ^ Mihai, Sidonia; Sitaru, Cassian (May–June 2007). "Immunopathology and molecular diagnosis of autoimmune bullous diseases". Journal of Cellular and Molecular Medicine 11 (3): 462–481. doi:10.1111/j.1582-4934.2007.00033.x. PMID 17521373.
- ^ Fine, Jo-David; Eady, Robin A. J.; Bauer, Eugene A.; Bauer, Johann W.; Bruckner-Tuderman, Leena; Heagerty, Adrian; Hintner, Helmut; Hovnanian, Alain; Jonkman, Marcel F.; Leigh, Irene; McGrath, John A.; Mellerio, Jemima E.; Murrell, Dedee F.; Shimizu, Hiroshi; Uitto, Jouni; Vahlquist, Anders; Woodley, David; Zambruno, Giovanna (2008). "The classification of inherited epidermolysis bullosa (EB): Report of the Third International Consensus Meeting on Diagnosis and Classification of EB". Journal of the American Academy of Dermatology 58 (6): 931–950. doi:10.1016/j.jaad.2008.02.004. PMID 18374450.
Sources
- Freedberg, Irwin M.; Eisen, Arthur Z.; Wolff, Klauss; Austen, K. Frank; Goldsmith, Lowell A.; Katz, Stephen I., eds. (2003). Fitzpatrick's Dermatology in General Medicine (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
- James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders. ISBN 0-7216-2921-0.
- Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0.
External links
- ebd at NIH/UW GeneTests
- 1959788591 at GPnotebook
|
Genetic disorder, extracellular: scleroprotein disease (excluding laminin and keratin)
|
|
| Collagen disease |
| COL1: |
- Osteogenesis imperfecta
- Ehlers–Danlos syndrome, types 1, 2, 7
|
|
| COL2: |
- Hypochondrogenesis
- Achondrogenesis type 2
- Stickler syndrome
- Marshall syndrome
- Spondyloepiphyseal dysplasia congenita
- Spondyloepimetaphyseal dysplasia, Strudwick type
- Kniest dysplasia (see also C2/11)
|
|
| COL3: |
- Ehlers–Danlos syndrome, types 3 & 4
|
|
| COL4: |
|
|
| COL5: |
- Ehlers–Danlos syndrome, types 1 & 2
|
|
| COL6: |
- Bethlem myopathy
- Ullrich congenital muscular dystrophy
|
|
| COL7: |
- Epidermolysis bullosa dystrophica
- Recessive dystrophic epidermolysis bullosa
- Bart syndrome
- Transient bullous dermolysis of the newborn
|
|
| COL8: |
|
|
| COL9: |
- Multiple epiphyseal dysplasia 2, 3, 6
|
|
| COL10: |
- Schmid metaphyseal chondrodysplasia
|
|
| COL11: |
- Weissenbacher–Zweymüller syndrome
- Otospondylomegaepiphyseal dysplasia (see also C2/11)
|
|
| COL17: |
|
|
|
| Laminin |
- Junctional epidermolysis bullosa
- Laryngoonychocutaneous syndrome
|
|
| Other |
- Congenital stromal corneal dystrophy
- Raine syndrome
- Urbach–Wiethe disease
- TECTA
|
|
|
see also fibrous proteins
|
Index of cells
|
|
| Description |
- Structure
- Organelles
- peroxisome
- cytoskeleton
- centrosome
- epithelia
- cilia
- mitochondria
- Membranes
- Membrane transport
- ion channels
- vesicular transport
- solute carrier
- ABC transporters
- ATPase
- oxidoreduction-driven
|
|
| Disease |
- Structural
- peroxisome
- cytoskeleton
- cilia
- mitochondria
- nucleus
- scleroprotein
- Membrane
- channelopathy
- solute carrier
- ATPase
- ABC transporters
- other
- extracellular ligands
- cell surface receptors
- intracellular signalling
- Vesicular transport
- Pore-forming toxins
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