Penetrance

Penetrance is 100% for biallelic KRT5 and KRT14 loss-of-function variants but appears to be less than 100% for heterozygous dominant-negative variants, as rare heterozygotes for dominant-negative variants are asymptomatic . Heterozygous pathogenic variants in PLEC and KLHL24 and biallelic pathogenic variants in CD151, DST, EXPH5, and PLEC are presumed to be fully penetrant as asymptomatic individuals have not been reported to date.

Source: GeneReviews — "Epidermolysis Bullosa Simplex"

Differential Diagnosis

The 2020 classification system names four major types of epidermolysis bullosa (EB):

• EB simplex (EBS)

• Junctional EB (JEB)

• Dystrophic EB (DEB)

• Kindler syndrome

All forms of EB are characterized by increased skin fragility (and often mucosa) and blistering with little or no trauma. Classification into major type is based on the location of blistering in relation to the dermal-epidermal junction of skin. Subtypes are predominantly determined by clinical features and supported by molecular diagnosis .

Table 6.

Clinical Features Observed in the Four Major Types of Epidermolysis Bullosa

Feature | Comment

Easy fragility of skin ( often mucosa) manifested by blistering w/little or no trauma | Shared by 4 major EB types

Source: GeneReviews — "Epidermolysis Bullosa Simplex"

Clinical Guidance

Excessive heat and sweating may exacerbate blistering, wounding, and infection in EBS. Poorly fitting or coarse-textured clothing and footwear can cause trauma and should be avoided. Avoiding activities that traumatize the skin (e.g., hiking, mountain biking, contact sports) can reduce skin damage; however, affected individuals who are determined to find ways to participate in these endeavors should be encouraged. Many individuals with EBS cannot use medical tape or Band-Aids® with adhesives.

Source: GeneReviews — "Epidermolysis Bullosa Simplex"

Therapies Under Investigation

Proposed approaches for gene therapy in EBS include the use of CRISPR/Cas9-mediated DNA repair , TALEN-mediated DNA repair , viral vectors carrying corrected gene products to transduce keratinocytes , RNA trans-splicing repair , addition of other functional proteins , induction of a compensating pathogenic variant via revertant mosaicism , and pathogenic variant-specific siRNAs . Systemic gentamicin may also induce PLEC readthrough and increase plectin expression in individuals with EBS, intermediate with muscular dystrophy caused by pathogenic nonsense variants . To date, however, no clinical trials of gene therapy for EBS have been completed.

Source: GeneReviews — "Epidermolysis Bullosa Simplex"