Epidermolysis bullosa dystrophica, also referred to as dystrophic epidermolysis bullosa (DEB) or dermolytic epidermolysis bullosa, is defined in the packet as a genetic skin disorder caused by mutations in the type VII collagen gene and characterized by blistering and scarring of the skin and mucous membranes. GeneReviews describes DEB as characterized by increased skin fragility and dystrophic or absent nails, with features usually present at birth. It divides DEB into recessive (RDEB) and dominant (DDEB) types, each with clinical subtypes based on severity. The packet lists onset categories of neonatal and infantile and a prevalence category of rare, with an estimate of 1-9 in 1,000,000.

The packet has no structured phenotype entries (phenotype count 0), so this section draws on the GeneReviews clinical description. GeneReviews reports skin fragility with blistering after minimal trauma that heals with milia and scarring, dystrophic or absent nails, and absent lingual papillae in the severe and intermediate recessive subtypes. Onset ranges from birth in severe RDEB to birth, infancy, childhood or adulthood in localized dominant DEB, where blisters are described as rare and primarily on the feet.

In severe RDEB, GeneReviews describes blisters present at birth or in the neonatal period, sometimes with aplasia cutis congenita of the extremities, and blistering that can affect the whole body including oral and esophageal mucosa and corneas. Chronic non-healing wounds with secondary infection are described as common. Oral involvement may lead to ankyloglossia, microstomia and dental caries. Esophageal blisters, webs and strictures can cause severe dysphagia, and gastroesophageal reflux and constipation are reported. Malnutrition may result in growth restriction and delayed puberty, and osteopenia, osteoporosis, vitamin and mineral deficiencies and anemia are described. Corneal erosions can lead to scarring and loss of vision. GeneReviews describes squamous cell carcinoma (SCC) as a feature of severe RDEB.

The packet's structured gene list (known_genes) and inheritance field (inheritance_patterns) are empty, so gene-level causes and structured inheritance are not certified in this packet and no gene symbol is named here. The packet definition attributes the condition to mutations in the type VII collagen gene. The packet does not supply a molecular mechanism field.

The GeneReviews chapter included in the packet states that DEB is inherited in an autosomal recessive (RDEB) or autosomal dominant (DDEB) manner, and that some variants of the causative gene are associated with both forms. It also reports compound heterozygous cases with one variant associated with DDEB and another with RDEB. For genotype-phenotype correlation, GeneReviews reports that severe RDEB is typically caused by biallelic variants resulting in no functional protein, intermediate RDEB generally by a glycine substitution in the triple helical domain on one allele and a premature stop codon on the other, and most DDEB by dominant-negative glycine substitutions in the collagenous triple helical domain of collagen VII. GeneReviews states that penetrance for DDEB is reduced, with unaffected variant carriers identified. These genetic details are attributed to GeneReviews alone.

The packet's diagnostic method fields are not populated, so this section follows the GeneReviews diagnosis chapter. GeneReviews states that DEB is suspected in individuals with skin fragility and blistering with minimal trauma that heals with milia and scarring, absent lingual papillae, blistering and erosions that may include aplasia cutis congenita, pseudosyndactyly, oral or esophageal scarring, and corneal erosions, and dystrophic or absent nails. Family history is described as consistent with autosomal recessive or autosomal dominant inheritance, and absence of a known family history does not preclude the diagnosis.

Per GeneReviews, the diagnosis is established in a proband with biallelic pathogenic or likely pathogenic variants (RDEB) or a heterozygous pathogenic or likely pathogenic variant (DDEB) identified by molecular genetic testing, or with characteristic skin biopsy findings on transmission electron microscopy (absent or abnormal anchoring fibrils) or immunofluorescent antigen mapping. GeneReviews describes molecular genetic testing as the preferred diagnostic method, with skin biopsy considered if molecular results are inconclusive or testing is not available. It states that variants of uncertain significance neither establish nor rule out the diagnosis, and that phenotypic severity and biopsy findings alone are not sufficient to determine mode of inheritance.

The packet has no approved_treatments or foundational_therapies fields and no verified FDA records, so this section reflects the GeneReviews management chapter and the orphan drug list. GeneReviews notes that international clinical practice guidelines for DEB have been published by DEBRA International, covering topics such as skin and wound care, pain care, oral health, anemia, constipation management, hand surgery and psychosocial care. It describes multidisciplinary supportive care aimed at quality of life, function and reduced complications, and lists evaluations following diagnosis across multiple organ systems. For skin, GeneReviews describes measures to minimize blister formation, such as protective handling, padding, soft clothing, and layered dressings.

Under targeted therapies, GeneReviews lists three products: beremagene geperpavec-svdt (Vyjuvek), a topical HSV-1 vector-based gene therapy described as FDA approved for wound treatment in those aged 6 months and older with molecularly confirmed RDEB or DDEB; prademagene zamikeracel (Zevaskyn), an autologous keratinocyte graft described as FDA approved for wound treatment in RDEB; and birch triterpenes (Filsuvez), a botanical drug product described as EMA and FDA approved for wound treatment in those aged 6 months and older with EB. These approval statements come from GeneReviews rather than a certified FDA field in the packet.

The orphan drug list contains one designation, a human decorin protein fused to a vascular homing peptide (sponsor Theravia), with status DESIGNATED for treatment of epidermolysis bullosa. A designation is not an approval.

The packet has no natural_history field, so prognosis is not certified as a structured element. GeneReviews describes severity as varying by subtype. For severe RDEB, it reports a lifetime risk of squamous cell carcinoma greater than 90% with significant metastatic potential, usually appearing in the third decade but as early as the second, and states that affected individuals often succumb to aggressive metastatic SCC and that satisfactory treatment is currently not available. GeneReviews describes phenotypic variability in RDEB as extreme, with some individuals having very mild disease that mimics DDEB. No overall life expectancy figure is supplied in the packet.

The packet lists ten clinical trial records. Interventional records include NCT07596927 (curcumin-based photodynamic therapy in epidermolysis bullosa, phase 4, Universidade Ceuma, active not recruiting), NCT06834035 (targeting collagen VII antibodies with IV IgG in DEB, phase 1, M. Peter Marinkovich, recruiting), NCT04171661 (self-assembled skin substitute, early phase 1, CHU de Quebec-Universite Laval, active not recruiting), NCT07193134 (a gene-modified skin substitute for RDEB, phase 1, CHU de Quebec-Universite Laval, recruiting), NCT04186650 (ex vivo gene therapy for RDEB using genetically corrected autologous skin equivalent grafts, phase 1, INSERM France, active not recruiting), NCT06917690 (Oleogel-S10 in Japanese patients with epidermolysis bullosa, phase 3, Chiesi Farmaceutici S.p.A., recruiting) and NCT05725018 (phase 3b study in DEB in new and previously EB-101 treated patients, Abeona Therapeutics, active not recruiting). Other records are NCT01019148 (characteristics of patients with RDEB, Stanford University), NCT05843994 (an artificial intelligence patient app for RDEB SCCs, Northwestern University) and NCT06563414 (natural history of corneal abrasions in DEB, Krystal Biotech).

GeneReviews states that stem cell approaches, gene-corrected fibroblasts, stop codon read-through, exon skipping, protein therapy and revertant mosaicism are being investigated. The research landscape digest classifies 109 publications, with basic science and preclinical work dominant, and notes gene therapy, biomarker and recent trial publications, plus 25 case reports and 10 reviews. The packet lists no patient organizations.