| Site of cleavage within the epidermis | Subtypes | Inheritance
Mutated gene
Targeted gene product | Clinical features |
| Suprabasal (cytolysis of suprabasal keratinocytes; intact blisters usually not clinically evident; keratinocytes form numerous interdigitating cellular protrusions; only few desmosomal remnants present) | Acantholytic EBS (EBS-acanth) | - Autosomal recessive
- DSP, JUP
- Desmoplakin (absent), plakoglobin (absent)
| - 5 cases of lethal acantholytic epidermolysis bullosa due to mutations in DSP and 1 due to JUP have been described[1-5]
- Generalized skin fragility with rapidly progressive epidermolysis and large sheets of detached skin with superficial erosions at birth; skin detachment on hands and feet in a glove and stocking pattern; complete disruption of the epidermal barrier without intact blisters or vesicles; no excessive granulation tissue
- Universal alopecia (complete absence of scalp hair, eyebrows, eyelashes despite discrete follicular openings on scalp), nail loss, and neonatal teeth
- Involvement of oropharynx, gastrointestinal, genitourinary, and respiratory tract with extensive suprabasal acantholytic separation
- Demise in neonatal period[1]
|
Skin fragility syndromes - Desmoplakin deficiency (EBS-desmoplakin; skin fragility-woolly hair syndrome)
- Plakoglobin deficiency (EBS-plakoglobin; skin fragility-plakoglobin deficiency)
- Plakophilin deficiency (EBS-plakophilin; skin fragility-ectodermal dysplasia syndrome)
| - Autosomal recessive
- DSP, JUP, PKP1
- Desmoplakin (reduced), plakoglobin (reduced), plakophilin-1 (absent or reduced)
| - Generalized skin fragility with trauma-induced and spontaneous superficial erosions from birth; palmoplantar keratoderma with painful, often disabling fissures (walking, bearing weight); nail dystrophy; alopecia
- Chronic cheilitis, perioral scale, perioral and lingual fissures
- Blepharitis, astigmatism
- Persistent abnormal hair (hypotrichosis, loss of eyelashes, complete alopecia; woolly hair)
- Esophageal strictures, constipation
- Growth retardation (usually below the third centile for height and weight)
- Variable clinical features include scattered scale-crust on the trunk and limbs, follicular hyperkeratosis, inflammatory scaly plaques in flexures, perianal erythema and erosions, pruritus; reduced sweating; dental caries; recurrent systemic infections; chronic diarrhea
|
| EBS superficialis | | - Blistering between stratum corneum and granulosum
- Superficial erosions with scarring and milia formation from birth or early infancy[6]
|
| Acral peeling skin syndrome[7] | - Autosomal recessive
- TGM5
- Transglutaminase-5
| - Superficial painless skin peeling (volar and dorsal aspects of hands, feet; elbows, knees)
- Acral blisters, erosions at birth/since infancy; pruritus aggravated by heat, sweating, humidity, mechanical trauma, exposure to water
- Spontaneous healing with residual erythema, burning sensation, pruritus, and hyperpigmentation
- No scarring or atrophy
|
| Basal (cytolysis of basal keratinocytes) | EBS, localized (EBS-loc, former Weber-Cockayne) | - Autosomal dominant
- KRT5, KRT14
- Keratin 5, keratin 14
| - Most common EBS subtype
- Mainly limited, regional involvement of palms and soles
- Clinical onset usually during infancy or, rarely, early adulthood
- Extracutaneous manifestations (other than clinically insignificant blisters within oral cavity during early childhood) rare[8]
|
| EBS, generalized severe (former Dowling-Meara) | - Autosomal dominant
- KRT5, KRT14
- Keratin 5, keratin 14
| - Generalized, peculiar herpetiform distribution (arcuate grouping) of blisters from birth (typically and best seen when patients have relatively milder disease activity[9])
- Atrophic scarring, milia formation, confluent palmoplantar hyperkeratosis, nail manifestations
- Often mucosal involvement
|
| EBS, generalized intermediate (includes former Koebner) | - Autosomal dominant
- KRT5, KRT14, EXPH5, DYS, KLHL24
- Keratin 5, keratin 14, exophilin 5, dystonin, Kelch-like family member 24
| - Widespread but less severe form that usually presents at birth
- Rarely eye involvement
|
| EBS-MP (EBS with mottled pigmentation) | - Autosomal dominant
- KRT5
- Keratin 5
| - Skin blistering with reticulate brown skin pigmentation, keratoderma, nail dystrophy
- Pigmentary lesions usually present in early childhood, but may become less distinctive or even imperceptible by adult life[9]
|
| EBS, migratory circinate | - Autosomal dominant
- KRT5
- Keratin 5
| - Blistering lesions on hands, legs, and feet from birth
- Annular migratory erythema with vesicles and crusts at the advancing edge
- Brown postinflammatory hyperpigmentation
- Improves in the first few years of life
|
| EBS with muscular dystrophy | - Autosomal recessive
- PLEC1
- Plectin
| - Generalized blistering from birth
- Atrophic scarring, milia formation, nail dystrophy and loss
- Granulation tissue formation and stenosis within respiratory tract
- Muscular dystrophy may either be present on or shortly after birth in a child with severe generalized skin involvement (usually appearing as "floppy" babies who are unable to easily lift their arms and legs), or, in others, may arise insidiously in later childhood or adulthood; this variant harbors a higher mortality rate from muscle involvement[8]
|
| EBS with pyloric atresia | - Autosomal recessive
- PLEC1, ITGA6, ITGB4
- Plectin, integrin-alpha-6, integrin-beta-4
| - Gestational hydramnion
- Generalized blistering of variable severity from birth, atrophic scarring[10-12]
- Association with aplasia cutis congenita[13]
- Mucosal involvement (protein losing enteropathy, diarrhea)
- Enamel hypoplasia, caries
- Anemia, growth retardation, contractures, cryptorchidism, high mortality
|
| EBS, autosomal recessive K14 | - Autosomal recessive
- KRT14[14]
- Keratin 14
| - Generalized blistering from birth (frequently anogenital), ichthyosiform plaques; rarely milia formation or atrophic scarring
- Involvement of oral cavity (caries) and genitourinary tract
- Growth retardation, constipation
|
| EBS, Ogna type | - Autosomal dominant
- PLEC1
- Plectin
| - Hemorrhagic blisters at predominantly acral sites from birth
- Onychogryphosis (markedly curved and deformed nails resembling ram's horns)[9]
|
| EBS, autosomal recessive-exophilin 5 deficiency | - Autosomal recessive
- EXPH5
- Exophilin-5 (Rab27B GTPase effector protein Slac2-b)
| - First described in 3 siblings born to first cousin parents[15]
- Disrupted keratinocyte adhesion within the lower epidermis with prominent skin fragility at birth
- Generalized trauma-induced, occasionally spontaneous scale, partly hemorrhagic crusts and intermittent skin blistering/erosions; bruising
- Healing with slightly atrophic scars and mild pigmentary mottling
- No involvement of mucous membranes, nails, and hair
- Symptomatic improvement within the first years of life with occasional small blisters, erosions, linear crusts at sites of mechanical trauma as the main feature
|
| EBS, autosomal recessive-BP230 deficiency | - Autosomal recessive
- DST/BPAG1-e
- Dystonin/coiled coil domain of epithelial isoform of bullous pemphigoid antigen-1 (BPAG1-e)
| - Only 1 reported case[14]
- Generalized, lifelong but relatively mild trauma-induced and spontaneous blistering (ankles, feet)
- Skin peeling; erosions, hemorrhage
- Nail dystrophy; normal hair growth
- Healing with postinflammatory hypo- and hyperpigmentation
- No scarring, milia formation, or mucosal blistering
- Episodes of collapse; recurrent bilateral headaches, transient episodes of arm numbness and weakness reported in index patient may represent manifestation of concomitant neurologic diagnosis of CADASIL syndrome
|
| Recessive EBS due to stabilizing mutations in the ubiquitin ligase enzyme that processes KRT14[16-18] | - Autosomal recessive
- KLHL-24
- Kelch-like family member 24
| - 26 cases in 3 reports from China, Israel, and the United Kingdom
- Quite marked birth traumas, especially the lower limbs
- Early involvement of trunk and arms
- Heal with subtle atrophic scarring
- Nail defects
- Oral ulceration
- Not much dyspigmentation
- Transient milia
- Alopecia ±
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