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Recessive dystrophic epidermolysis bullosa(RDEB)

MedGen UID:
36311
Concept ID:
C0079474
Disease or Syndrome
Synonyms: DYSTROPHIC EPIDERMOLYSIS BULLOSA, AUTOSOMAL RECESSIVE; Epidermolysis Bullosa Distrophica Autosomal Recessive (RDEB); EPIDERMOLYSIS BULLOSA DYSTROPHICA, AUTOSOMAL RECESSIVE; EPIDERMOLYSIS BULLOSA DYSTROPHICA, GENERALIZED SEVERE, AUTOSOMAL RECESSIVE; EPIDERMOLYSIS BULLOSA DYSTROPHICA, HALLOPEAU-SIEMENS TYPE; Hallopeau-Siemens Disease; RDEB; severe generalized recessive dystrophic epidermolysis bullosa
SNOMED CT: Recessive dystrophic epidermolysis bullosa (48528004); Dysplastic epidermolysis bullosa dystrophica (48528004); Polydysplastic epidermolysis bullosa (48528004)
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).
 
Genes (locations): COL7A1 (3p21.31); MMP1 (11q22.2)
 
Monarch Initiative: MONDO:0009179
OMIM®: 226600
Orphanet: ORPHA79408

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
Autosomal recessive dystrophic epidermolysis bullosa is a severe skin disorder beginning at birth and characterized by recurrent blistering at the level of the sublamina densa beneath the cutaneous basement membrane. This results in mutilating scarring and contractures of the hands, feet, and joints. Patients also developed strictures of the gastrointestinal tract from mucosal involvement, which can lead to poor nutrition. Affected individuals have an increased risk of developing aggressive squamous cell carcinoma (Christiano et al., 1996; Varki et al., 2007). Allelic disorders include autosomal dominant DEB (DDEB; 131750), in which the phenotype is less severe, and nonsyndromic congenital nail disorder-8 (NDNC8; 607523), which has been found to segregate as an autosomal dominant trait in heterozygous carriers in some families with recessive DEB.  http://www.omim.org/entry/226600
From MedlinePlus Genetics
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.

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.

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.

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.

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.  https://medlineplus.gov/genetics/condition/dystrophic-epidermolysis-bullosa

Clinical features

From HPO
Squamous cell carcinoma
MedGen UID:
2874
Concept ID:
C0007137
Neoplastic Process
The presence of squamous cell carcinoma of the skin.
Mitten deformity
MedGen UID:
369963
Concept ID:
C1969236
Congenital Abnormality
Fusion of the hands and feet by a thin membrane of skin (scarring) seen in forms of dystrophic epidermolysis bullosa and leading to a "mitten" hand deformity.
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Infrequent or difficult evacuation of feces.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Malnutrition
MedGen UID:
56429
Concept ID:
C0162429
Disease or Syndrome
A deficiency in the intake of energy and nutrients.
Boerhaave syndrome
MedGen UID:
65948
Concept ID:
C0238115
Disease or Syndrome
The occurrence of the full-thickness tear (perforation) of the wall of the esophagus.
Abnormal esophagus morphology
MedGen UID:
539700
Concept ID:
C0266126
Congenital Abnormality
A structural abnormality of the esophagus.
Esophageal stricture
MedGen UID:
1637009
Concept ID:
C4551650
Disease or Syndrome
A pathological narrowing of the esophagus that is caused by the development of a ring of scar tissue that constricts the esophageal lumen.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Corneal scarring
MedGen UID:
83899
Concept ID:
C0349702
Finding
Replacement of corneal tissue with scar tissue as a result of injury to the deeper layers of the cornea.
Conjunctivitis
MedGen UID:
1093
Concept ID:
C0009763
Disease or Syndrome
Inflammation of the conjunctiva.
Enamel hypoplasia
MedGen UID:
3730
Concept ID:
C0011351
Disease or Syndrome
Developmental hypoplasia of the dental enamel.
Narrow mouth
MedGen UID:
44435
Concept ID:
C0026034
Congenital Abnormality
Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective).
Alopecia
MedGen UID:
7982
Concept ID:
C0002170
Finding
A noncongenital process of hair loss, which may progress to partial or complete baldness.
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.
Fragile skin
MedGen UID:
66826
Concept ID:
C0241181
Finding
Skin that splits easily with minimal injury.
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.
Oral mucosal blisters
MedGen UID:
208888
Concept ID:
C0853945
Sign or Symptom
Blisters arising in the mouth.
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.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVRecessive dystrophic epidermolysis bullosa

Professional guidelines

PubMed

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
Li AW, Prindaville B, Bateman ST, Gibson TE, Wiss K
Pediatr Dermatol 2017 Nov;34(6):647-655. Epub 2017 Sep 25 doi: 10.1111/pde.13276. PMID: 28944966
Nevala-Plagemann C, Lee C, Tolar J
Cytotherapy 2015 Jun;17(6):786-795. Epub 2015 Mar 18 doi: 10.1016/j.jcyt.2015.03.006. PMID: 25795271Free PMC Article

Recent clinical studies

Etiology

Subramaniam KS, Antoniou MN, McGrath JA, Lwin SM
Br J Dermatol 2022 Apr;186(4):609-619. Epub 2022 Apr 1 doi: 10.1111/bjd.20910. PMID: 34862606
Tartaglia G, Cao Q, Padron ZM, South AP
Int J Mol Sci 2021 May 12;22(10) doi: 10.3390/ijms22105104. PMID: 34065916Free PMC Article
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
Boria F, Maseda R, Martín-Cameán M, De la Calle M, de Lucas R
Actas Dermosifiliogr (Engl Ed) 2019 Jan-Feb;110(1):50-52. Epub 2017 Dec 6 doi: 10.1016/j.ad.2017.06.024. PMID: 29203033
Has C, He Y
Cell Tissue Res 2017 Jul;369(1):63-73. Epub 2017 Apr 22 doi: 10.1007/s00441-017-2623-y. PMID: 28432467

Diagnosis

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
Robertson SJ, Prodinger C, Liu L, Skilbeck C, Petrof G, Martinez AE, Mellerio JE, Greenblatt DT
Clin Exp Dermatol 2022 Apr;47(4):717-723. Epub 2022 Jan 5 doi: 10.1111/ced.15029. PMID: 34826142
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
Li AW, Prindaville B, Bateman ST, Gibson TE, Wiss K
Pediatr Dermatol 2017 Nov;34(6):647-655. Epub 2017 Sep 25 doi: 10.1111/pde.13276. PMID: 28944966
Woodley DT, Chen M
J Invest Dermatol 2015 Jul;135(7):1705-1707. doi: 10.1038/jid.2015.149. PMID: 26066885

Therapy

So JY, Nazaroff J, Iwummadu CV, Harris N, Gorell ES, Fulchand S, Bailey I, McCarthy D, Siprashvili Z, Marinkovich MP, Tang JY, Chiou AS
Orphanet J Rare Dis 2022 Oct 17;17(1):377. doi: 10.1186/s13023-022-02546-9. PMID: 36253825Free PMC Article
Gurevich I, Agarwal P, Zhang P, Dolorito JA, Oliver S, Liu H, Reitze N, Sarma N, Bagci IS, Sridhar K, Kakarla V, Yenamandra VK, O'Malley M, Prisco M, Tufa SF, Keene DR, South AP, Krishnan SM, Marinkovich MP
Nat Med 2022 Apr;28(4):780-788. Epub 2022 Mar 28 doi: 10.1038/s41591-022-01737-y. PMID: 35347281Free PMC Article
Zauner R, Wimmer M, Dorfer S, Ablinger M, Koller U, Piñón Hofbauer J, Guttmann-Gruber C, Bauer JW, Wally V
Int J Mol Sci 2022 Jan 17;23(2) doi: 10.3390/ijms23021007. PMID: 35055192Free PMC Article
Chen F, Guo Y, Zhou K, Deng D, Yue W, Yang W, Zhang B, Li Y, Liang J, Li M, Yao Z
Clin Genet 2022 Jan;101(1):110-115. Epub 2021 Sep 15 doi: 10.1111/cge.14062. PMID: 34494659
Woodley DT, Chen M
J Invest Dermatol 2015 Jul;135(7):1705-1707. doi: 10.1038/jid.2015.149. PMID: 26066885

Prognosis

Dieter K, Niebergall-Roth E, Daniele C, Fluhr S, Frank NY, Ganss C, Kiritsi D, McGrath JA, Tolar J, Frank MH, Kluth MA
Cytotherapy 2023 Jul;25(7):782-788. Epub 2023 Mar 1 doi: 10.1016/j.jcyt.2023.01.015. PMID: 36868990Free PMC Article
Zauner R, Wimmer M, Dorfer S, Ablinger M, Koller U, Piñón Hofbauer J, Guttmann-Gruber C, Bauer JW, Wally V
Int J Mol Sci 2022 Jan 17;23(2) doi: 10.3390/ijms23021007. PMID: 35055192Free PMC Article
Onoufriadis A, Proudfoot LE, Ainali C, Torre D, Papanikolaou M, Rayinda T, Rashidghamat E, Danarti R, Mellerio JE, Ma'ayan A, McGrath JA
Exp Dermatol 2022 Mar;31(3):420-426. Epub 2021 Nov 2 doi: 10.1111/exd.14481. PMID: 34694680
von Bischhoffshausen S, Ivulic D, Alvarez P, Schuffeneger VC, Idiaquez J, Fuentes C, Morande P, Fuentes I, Palisson F, Bennett DLH, Calvo M
Brain 2017 May 1;140(5):1238-1251. doi: 10.1093/brain/awx069. PMID: 28369282Free PMC Article
Woodley DT, Chen M
J Invest Dermatol 2015 Jul;135(7):1705-1707. doi: 10.1038/jid.2015.149. PMID: 26066885

Clinical prediction guides

So JY, Nazaroff J, Iwummadu CV, Harris N, Gorell ES, Fulchand S, Bailey I, McCarthy D, Siprashvili Z, Marinkovich MP, Tang JY, Chiou AS
Orphanet J Rare Dis 2022 Oct 17;17(1):377. doi: 10.1186/s13023-022-02546-9. PMID: 36253825Free PMC Article
Robertson SJ, Prodinger C, Liu L, Skilbeck C, Petrof G, Martinez AE, Mellerio JE, Greenblatt DT
Clin Exp Dermatol 2022 Apr;47(4):717-723. Epub 2022 Jan 5 doi: 10.1111/ced.15029. PMID: 34826142
Chen F, Guo Y, Zhou K, Deng D, Yue W, Yang W, Zhang B, Li Y, Liang J, Li M, Yao Z
Clin Genet 2022 Jan;101(1):110-115. Epub 2021 Sep 15 doi: 10.1111/cge.14062. PMID: 34494659
Kiritsi D, Dieter K, Niebergall-Roth E, Fluhr S, Daniele C, Esterlechner J, Sadeghi S, Ballikaya S, Erdinger L, Schauer F, Gewert S, Laimer M, Bauer JW, Hovnanian A, Zambruno G, El Hachem M, Bourrat E, Papanikolaou M, Petrof G, Kitzmüller S, Ebens CL, Frank MH, Frank NY, Ganss C, Martinez AE, McGrath JA, Tolar J, Kluth MA
JCI Insight 2021 Nov 22;6(22) doi: 10.1172/jci.insight.151922. PMID: 34665781Free PMC Article
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

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

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