EPIDERMOLYSIS BULLOSA

Epidermolysis Bullosa — the first genetic skin disease with an FDA-approved gene therapy (Vyjuvek, 2023), where molecular diagnosis of the specific gene and variant determines treatment eligibility and wound management approach.

Whole genome sequencing evaluates all 20+ epidermolysis bullosa genes simultaneously — KRT5, KRT14, COL7A1, COL17A1, LAMB3, and others — providing the molecular diagnosis required for gene therapy eligibility and accurate prognosis.

COL7A1
KRT5
KRT14
LAMB3
COL17A1

About this condition

Epidermolysis Bullosa

Epidermolysis bullosa (EB) is a group of inherited skin fragility disorders characterized by blistering and erosion of the skin and mucous membranes in response to minimal mechanical trauma. EB encompasses over 30 subtypes caused by variants in more than 20 genes encoding structural proteins of the dermal-epidermal junction. The four major types — EB simplex (EBS, primarily KRT5/KRT14), junctional EB (JEB, primarily LAMB3/LAMA3/COL17A1), dystrophic EB (DEB, COL7A1), and Kindler EB (FERMT1) — differ dramatically in severity, affected skin layer, and prognosis.

Dystrophic EB caused by biallelic COL7A1 loss-of-function variants (recessive DEB) is among the most severe forms: absent type VII collagen results in blistering below the lamina densa, producing chronic wounds, scarring contractures of the hands (mitten deformity), esophageal strictures, and a dramatically elevated risk of aggressive squamous cell carcinoma — the leading cause of death, with median onset in the third decade. Junctional EB (severe generalized form) can be lethal in infancy. EB simplex is generally the mildest major type but can cause significant morbidity.

Beremagene geperpavec (Vyjuvek), an HSV-1-based topical gene therapy delivering functional COL7A1, received FDA approval in May 2023 for treatment of wounds in dystrophic EB patients 6 months and older with COL7A1 pathogenic variants. This is the first FDA-approved gene therapy for any dermatological condition. Additional gene and cell therapy approaches are in clinical development for other EB subtypes. Molecular diagnosis confirming the specific EB gene and variant is required for Vyjuvek eligibility and for enrollment in all gene therapy clinical trials.

Beremagene geperpavec (Vyjuvek) — FDA approved May 2023 — is the first gene therapy for any skin disease. It delivers functional COL7A1 to dystrophic EB wounds. Molecular confirmation of COL7A1 variants is required for prescribing.

Gene locus: COL7A1 (3p21.31), KRT5 (12q13.13), KRT14 (17q21.2), LAMB3 (1q32.2), COL17A1 (10q25.1)

20+ genes cause EB. Skin biopsy with immunofluorescence narrows the type but does not provide the molecular diagnosis required for gene therapy eligibility or accurate genetic counseling.

Vyjuvek gene therapy requires confirmed COL7A1 variants — clinical or biopsy diagnosis alone is not sufficient

Beremagene geperpavec is indicated specifically for wounds in patients with dystrophic EB caused by COL7A1 pathogenic variants. Skin biopsy with immunofluorescence mapping can identify absent or reduced type VII collagen — but does not provide the molecular variant identification required for Vyjuvek prescribing or for enrollment in clinical trials. Additionally, knowing the specific COL7A1 variants determines eligibility for other emerging therapies including exon-skipping antisense oligonucleotides that target specific exons. Whole genome sequencing provides the definitive molecular diagnosis.

Prenatal diagnosis in families with severe EB enables delivery planning and immediate neonatal skin management

Families with a prior child affected by severe junctional or recessive dystrophic EB require prenatal molecular diagnosis to determine whether subsequent pregnancies are affected. Affected neonates require immediate specialized skin management at delivery — non-adherent dressings, careful handling to prevent iatrogenic blistering, and neonatal intensive care in some cases. Knowing the fetal genotype before delivery enables planned cesarean section (to reduce skin trauma) at a facility with EB-experienced neonatal care. This requires confirmed parental COL7A1, LAMB3, or other EB gene variants from whole genome sequencing.

Epidermolysis Bullosa — the first genetic skin disease with an FDA-approved gene therapy (Vyjuvek, 2023), where molecular diagnosis of the specific gene and variant determines treatment eligibility and wound management approach.

Epidermolysis Bullosa

20+ genes cause EB. Skin biopsy with immunofluorescence narrows the type but does not provide the molecular diagnosis required for gene therapy eligibility or accurate genetic counseling.

Vyjuvek gene therapy requires confirmed COL7A1 variants — clinical or biopsy diagnosis alone is not sufficient

Prenatal diagnosis in families with severe EB enables delivery planning and immediate neonatal skin management

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