U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Generalized dominant dystrophic epidermolysis bullosa(DDEB)

MedGen UID:
140935
Concept ID:
C0432322
Congenital Abnormality
Synonyms: DDEB; DDEB, generalized; DDEB-gen; DYSTROPHIC EPIDERMOLYSIS BULLOSA, AUTOSOMAL DOMINANT; Epidermolysis bullosa dystrophica, autosomal dominant
SNOMED CT: Dominant dystrophic epidermolysis bullosa of Pasini (75875004); Albopapuloid dystrophic epidermolysis bullosa of Pasini (75875004); Dominant dystrophic epidermolysis bullosa, albopapular type (75875004); Epidermolysis bullosa dystrophica, Pasini type (75875004)
Modes of inheritance:
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:0007549
OMIM®: 131750
Orphanet: ORPHA231568

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 descriptions

From OMIM
Epidermolysis bullosa dystrophica is a clinically heterogeneous disorder characterized by blistering and scarring of the skin and mucous membranes in response to mechanical force. Microscopic examination of the skin shows cleavage below the basement membrane within the papillary dermis. All forms are caused by mutation in the COL7A1 gene. Fine et al. (2000) proposed that the Cockayne-Touraine and Pasini subtypes of dystrophic epidermolysis bullosa be combined into 1 category known as 'dominant dystrophic epidermolysis bullosa' (DDEB), since both are caused by mutations in the COL7A1 gene and show overlapping clinical features. Epidermolysis bullosa simplex (see, e.g., 131800) and epidermolysis bullosa junctional (see, e.g., 226700) are clinically and genetically distinct disorders characterized by tissue separation at the levels of the basal keratinocyte layer and lamina lucida, respectively.  http://www.omim.org/entry/131750
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

Clinical features

From HPO
Atrophic scars
MedGen UID:
57875
Concept ID:
C0162154
Pathologic Function
Scars that form a depression compared to the level of the surrounding skin because of damage to the collagen, fat or other tissues below the skin.
Nail dystrophy
MedGen UID:
66368
Concept ID:
C0221260
Disease or Syndrome
Onychodystrophy (nail dystrophy) refers to nail changes apart from changes of the color (nail dyschromia) and involves partial or complete disruption of the various keratinous layers of the nail plate.
Milia
MedGen UID:
87528
Concept ID:
C0345996
Anatomical Abnormality
Presence of multiple small cysts containing keratin (skin protein) and presenting as tiny pearly-white bumps just under the surface of the skin.
Nail dysplasia
MedGen UID:
331737
Concept ID:
C1834405
Congenital Abnormality
The presence of developmental dysplasia of the nail.
Abnormal blistering of the skin
MedGen UID:
412159
Concept ID:
C2132198
Finding
The presence of one or more bullae on the skin, defined as fluid-filled blisters more than 5 mm in diameter with thin walls.
Sub-lamina densa cleavage
MedGen UID:
1778332
Concept ID:
C5539822
Finding
A type of blistering in which the cleavage plane of blisters is located below the lamina densa.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVGeneralized dominant dystrophic epidermolysis bullosa
Follow this link to review classifications for Generalized dominant dystrophic epidermolysis bullosa in Orphanet.

Professional guidelines

PubMed

Arline Diana I, Tan EC, Gondokaryono SP, Koh MJ, Dwiyana RF, Rahardja JI, Yogya Y, Rafi'ee K, Suwarsa O
Australas J Dermatol 2023 Nov;64(4):e327-e332. Epub 2023 Jul 14 doi: 10.1111/ajd.14121. PMID: 37452458
Liy-Wong C, Tarango C, Pope E, Coates T, Bruckner AL, Feinstein JA, Schwieger-Briel A, Hubbard LD, Jane C, Torres-Pradilla M, Zmazek M, Lara-Corrales I
Orphanet J Rare Dis 2023 Feb 23;18(1):38. doi: 10.1186/s13023-022-02448-w. PMID: 36823529Free PMC Article
Chen F, Wei R, Deng D, Zhang X, Cao Y, Pan C, Wang Y, Cao Q, Wang J, Zeng M, Huang L, Gu Y, Yao Z, Li M
J Eur Acad Dermatol Venereol 2023 Feb;37(2):411-419. Epub 2022 Nov 5 doi: 10.1111/jdv.18692. PMID: 36287101

Recent clinical studies

Etiology

Arline Diana I, Tan EC, Gondokaryono SP, Koh MJ, Dwiyana RF, Rahardja JI, Yogya Y, Rafi'ee K, Suwarsa O
Australas J Dermatol 2023 Nov;64(4):e327-e332. Epub 2023 Jul 14 doi: 10.1111/ajd.14121. PMID: 37452458
Kern JS, Sprecher E, Fernandez MF, Schauer F, Bodemer C, Cunningham T, Löwe S, Davis C, Sumeray M, Bruckner AL, Murrell DF; EASE investigators
Br J Dermatol 2023 Jan 23;188(1):12-21. doi: 10.1093/bjd/ljac001. PMID: 36689495
Chen F, Wei R, Deng D, Zhang X, Cao Y, Pan C, Wang Y, Cao Q, Wang J, Zeng M, Huang L, Gu Y, Yao Z, Li M
J Eur Acad Dermatol Venereol 2023 Feb;37(2):411-419. Epub 2022 Nov 5 doi: 10.1111/jdv.18692. PMID: 36287101
Polizzi A, Santonocito S, Patini R, Quinzi V, Mummolo S, Leonardi R, Bianchi A, Isola G
Biomed Res Int 2022;2022:6493156. Epub 2022 May 31 doi: 10.1155/2022/6493156. PMID: 35686231Free PMC Article
Dourado Alcorte M, Sogayar MC, Demasi MA
Expert Opin Ther Pat 2019 May;29(5):327-337. Epub 2019 Apr 24 doi: 10.1080/13543776.2019.1608181. PMID: 31017019

Diagnosis

Arline Diana I, Tan EC, Gondokaryono SP, Koh MJ, Dwiyana RF, Rahardja JI, Yogya Y, Rafi'ee K, Suwarsa O
Australas J Dermatol 2023 Nov;64(4):e327-e332. Epub 2023 Jul 14 doi: 10.1111/ajd.14121. PMID: 37452458
Liy-Wong C, Tarango C, Pope E, Coates T, Bruckner AL, Feinstein JA, Schwieger-Briel A, Hubbard LD, Jane C, Torres-Pradilla M, Zmazek M, Lara-Corrales I
Orphanet J Rare Dis 2023 Feb 23;18(1):38. doi: 10.1186/s13023-022-02448-w. PMID: 36823529Free PMC Article
Chen F, Wei R, Deng D, Zhang X, Cao Y, Pan C, Wang Y, Cao Q, Wang J, Zeng M, Huang L, Gu Y, Yao Z, Li M
J Eur Acad Dermatol Venereol 2023 Feb;37(2):411-419. Epub 2022 Nov 5 doi: 10.1111/jdv.18692. PMID: 36287101
Yadav RS, Jayswal A, Shrestha S, Gupta SK, Paudel U
JNMA J Nepal Med Assoc 2018 Sep-Oct;56(213):879-882. doi: 10.31729/jnma.3791. PMID: 31065125Free PMC Article
Burkhart CG, Ruppert ES
Clin Pediatr (Phila) 1981 Aug;20(8):493-6. doi: 10.1177/000992288102000801. PMID: 7249491

Therapy

Kern JS, Sprecher E, Fernandez MF, Schauer F, Bodemer C, Cunningham T, Löwe S, Davis C, Sumeray M, Bruckner AL, Murrell DF; EASE investigators
Br J Dermatol 2023 Jan 23;188(1):12-21. doi: 10.1093/bjd/ljac001. PMID: 36689495
Naso G, Petrova A
Br Med Bull 2020 Dec 15;136(1):30-45. doi: 10.1093/bmb/ldaa029. PMID: 32888294
Ertop P, Vural S, Gökpınar Ili E, Durmaz CD, Heper AO, McGrath JA, Ilgın RH, Boyvat A
Int J Dermatol 2020 Jul;59(7):851-855. Epub 2020 Jun 7 doi: 10.1111/ijd.14951. PMID: 32506551
Bonafont J, Mencía Á, García M, Torres R, Rodríguez S, Carretero M, Chacón-Solano E, Modamio-Høybjør S, Marinas L, León C, Escamez MJ, Hausser I, Del Río M, Murillas R, Larcher F
Mol Ther 2019 May 8;27(5):986-998. Epub 2019 Mar 15 doi: 10.1016/j.ymthe.2019.03.007. PMID: 30930113Free PMC Article
Kirkorian AY, Weitz NA, Tlougan B, Morel KD
Pediatr Dermatol 2014 Jan-Feb;31(1):33-7. Epub 2013 Nov 14 doi: 10.1111/pde.12243. PMID: 24224977

Prognosis

Ali FM, Zhou J, Wang M, Wang Q, Sun L, Mshenga MM, Lu H
BMC Pediatr 2024 Apr 5;24(1):242. doi: 10.1186/s12887-024-04715-0. PMID: 38580989Free PMC Article
Arline Diana I, Tan EC, Gondokaryono SP, Koh MJ, Dwiyana RF, Rahardja JI, Yogya Y, Rafi'ee K, Suwarsa O
Australas J Dermatol 2023 Nov;64(4):e327-e332. Epub 2023 Jul 14 doi: 10.1111/ajd.14121. PMID: 37452458
Merzel Šabović EK, Luzar B, Wechtersbach K, Dolenc-Voljč M
Acta Dermatovenerol Croat 2022 Nov;30(3):151-156. PMID: 36812272
Polizzi A, Santonocito S, Patini R, Quinzi V, Mummolo S, Leonardi R, Bianchi A, Isola G
Biomed Res Int 2022;2022:6493156. Epub 2022 May 31 doi: 10.1155/2022/6493156. PMID: 35686231Free PMC Article
Kocher T, March OP, Bischof J, Liemberger B, Hainzl S, Klausegger A, Hoog A, Strunk D, Bauer JW, Koller U
J Invest Dermatol 2020 Oct;140(10):1985-1993.e5. Epub 2020 Mar 3 doi: 10.1016/j.jid.2020.02.012. PMID: 32142798

Clinical prediction guides

Illmer J, Zauner R, Piñón Hofbauer J, Wimmer M, Gruner S, Ablinger M, Bischof J, Dorfer S, Hainzl S, Tober V, Bergson S, Sarig O, Samuelov L, Guttmann-Gruber C, Shalom-Feuerstein R, Sprecher E, Koller U, Laimer M, Bauer JW, Wally V
Br J Dermatol 2023 Dec 20;190(1):80-93. doi: 10.1093/bjd/ljad335. PMID: 37681509
Chen F, Wei R, Deng D, Zhang X, Cao Y, Pan C, Wang Y, Cao Q, Wang J, Zeng M, Huang L, Gu Y, Yao Z, Li M
J Eur Acad Dermatol Venereol 2023 Feb;37(2):411-419. Epub 2022 Nov 5 doi: 10.1111/jdv.18692. PMID: 36287101
Tang JY, Marinkovich MP, Lucas E, Gorell E, Chiou A, Lu Y, Gillon J, Patel D, Rudin D
Orphanet J Rare Dis 2021 Apr 13;16(1):175. doi: 10.1186/s13023-021-01811-7. PMID: 33849616Free PMC Article
Kocher T, March OP, Bischof J, Liemberger B, Hainzl S, Klausegger A, Hoog A, Strunk D, Bauer JW, Koller U
J Invest Dermatol 2020 Oct;140(10):1985-1993.e5. Epub 2020 Mar 3 doi: 10.1016/j.jid.2020.02.012. PMID: 32142798
Bruckner-Tuderman L
Exp Dermatol 1992 Oct;1(3):115-20. doi: 10.1111/j.1600-0625.1992.tb00001.x. PMID: 1365310

Recent systematic reviews

Tang JY, Marinkovich MP, Lucas E, Gorell E, Chiou A, Lu Y, Gillon J, Patel D, Rudin D
Orphanet J Rare Dis 2021 Apr 13;16(1):175. doi: 10.1186/s13023-021-01811-7. PMID: 33849616Free PMC Article
Krämer S, Lucas J, Gamboa F, Peñarrocha Diago M, Peñarrocha Oltra D, Guzmán-Letelier M, Paul S, Molina G, Sepúlveda L, Araya I, Soto R, Arriagada C, Lucky AW, Mellerio JE, Cornwall R, Alsayer F, Schilke R, Antal MA, Castrillón F, Paredes C, Serrano MC, Clark V
Spec Care Dentist 2020 Nov;40 Suppl 1(Suppl 1):3-81. doi: 10.1111/scd.12511. PMID: 33202040Free PMC Article
Montaudié H, Chiaverini C, Sbidian E, Charlesworth A, Lacour JP
Orphanet J Rare Dis 2016 Aug 20;11(1):117. doi: 10.1186/s13023-016-0489-9. PMID: 27544590Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...