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Dystrophic Epidermolysis Bullosa

Synonyms: DEB, Epidermolysis Bullosa Dystrophica

, MD, , MD, MSc, and , MMSc, CGC.

Author Information and Affiliations

Initial Posting: ; Last Revision: May 8, 2025.

Estimated reading time: 40 minutes

Summary

Clinical characteristics.

Dystrophic epidermolysis bullosa (DEB) is characterized by skin fragility manifested by blistering and erosions with minimal trauma. Many individuals also have dystrophic or absent nails. DEB is divided into two major types depending on inheritance pattern: recessive dystrophic epidermolysis bullosa (RDEB) and dominant dystrophic epidermolysis bullosa (DDEB).

Clinical findings in severe RDEB include skin fragility manifested by blistering and erosions 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 and mouth opening. Esophageal erosions can lead to webs and strictures that can cause severe dysphagia. Malnutrition with vitamin and mineral deficiency may lead to growth deficiency in young children. Corneal erosions can lead to scarring and loss of vision. Blistering of the hands and feet followed by scarring results in contractures and pseudosyndactyly. The lifetime risk of aggressive squamous cell carcinoma (SCC) is greater than 90%.

In contrast, the blistering in intermediate RDEB may be localized to hands, feet, knees, and elbows with or without involvement of flexural areas and the trunk, and without severe scarring.

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.

Diagnosis/testing.

The diagnosis of DEB is established in a proband with characteristic clinical findings and biallelic COL7A1 pathogenic variants (for RDEB) or a heterozygous pathogenic variant in COL7A1 (for DDEB) identified by molecular genetic testing. Skin biopsy using transmission electron microscopy and/or immunofluorescent antibody/antigen mapping can be considered in those with inconclusive molecular genetic testing or if genetic mutation analysis is not available.

Management.

Targeted therapies: Beremagene geperpavec-svdt topical therapy in those with molecularly confirmed DEB; birch triterpenes / birch bark extract topical therapy.

Supportive care: Minimize new blisters with education of caretakers, wrapping and padding extremities, and soft and loose-fitting clothing; vaginal delivery is the preferred method, but in certain circumstances, cesarian delivery may be recommended to prevent trauma of an affected fetus; encourage play that reduces risk of skin trauma; dressing and padding to protect bone prominences; new blisters should be lanced, drained, and in most cases dressed with nonadherent dressings, covered with padding for stability and protection, and secured with an elastic mesh-like wrap for integrity (e.g., burn net). Antibiotics and antiseptics for wound infection; appropriate footwear and physical therapy to preserve ambulation; topical, oral, and psychological therapies for pain and itch; specialized treatment of SCC; good dental care; dilation of esophageal strictures and webs to improve swallowing; management of constipation. Fluid and electrolyte management as needed; nutritional support including feeding gastrostomy tube, vitamin A, zinc, selenium, and carnitine supplementation. Anemia is treated with iron supplements and transfusions as needed. Eye lubricants and protective contact lenses may prevent corneal abrasions. Angiotensin-converting enzyme inhibitors for cardiomyopathy; treatment of urologic and kidney manifestations per urologist and nephrologist. Occupational and physical therapy may help prevent hand and other joint contractures. Surgical release of fingers often needs to be repeated. Calcium and vitamin D supplementation and bisphosphonates as needed for osteoporosis. Estrogen replacement as needed for delayed puberty; suppression of menses can prevent exacerbation of anemia; psychosocial support.

Surveillance: Thorough skin examination at each visit and as recommended by dermatologist; evaluation of crusted, non-healing, and painful lesions as well as those with exuberant scar tissue at least annually beginning at age ten years; biopsies of suspicious lesions for evidence of SCC. Assess oral mucosa, feeding, esophageal involvement, gastrointestinal manifestations, growth, nutrition, hand function, footwear, mobility, and family needs at each visit. Serum vitamin A, selenium, carnitine, zinc, 25-hydroxyvitamin D3, complete blood count, iron studies, and urinalysis every six to 12 months; ophthalmology examinations as needed; annual echocardiogram to identify dilated cardiomyopathy starting at age two years; annual spine radiographs and DXA scan to assess for osteoporosis starting at age six years or earlier in those with unexplained pain and/or fractures; evaluation of pubertal status at each visit beginning at age ten to 12 years.

Agents/circumstances to avoid: Nasogastric tubes are discouraged because of oral and esophageal fragility; poorly fitting or coarse-textured clothing and footwear; activities/bandages that traumatize the skin.

Evaluation of relatives at risk: Molecular genetic testing of at-risk relatives should be offered to permit early diagnosis and treatment in order to identify those who would benefit from management of trauma to the skin.

Genetic counseling.

DEB is inherited in either an autosomal dominant (DDEB) or autosomal recessive (RDEB) manner. Some COL7A1 pathogenic variants are associated with both DDEB and RDEB. Molecular characterization of the COL7A1 pathogenic variants is the only accurate method to determine mode of inheritance and recurrence risk; phenotype severity and skin biopsy findings alone are not sufficient.

DDEB: About 70% of individuals diagnosed with DDEB are reported to have an affected parent. If a parent of a proband with DDEB is affected and/or is known to be heterozygous for the COL7A1 pathogenic variant, the risk to the sibs is 50%. Each child of an individual with DDEB has a 50% chance of inheriting the pathogenic variant. Intrafamilial clinical variability and reduced penetrance have been observed among heterozygous family members.

RDEB: If both parents are known to be heterozygous for a COL7A1 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being heterozygous, and a 25% chance of inheriting neither of the familial pathogenic variants. Heterozygous sibs of a proband with RDEB are typically asymptomatic, although some pathogenic variants are associated with both DDEB and RDEB.

Once the COL7A1 pathogenic variant(s) have been identified in an affected family member, prenatal and preimplantation genetic testing are possible.

GeneReview Scope

Dystrophic Epidermolysis Bullosa (DEB): Included Phenotypes
  • Recessive DEB (RDEB)
    • Severe
    • Intermediate
    • Inversa
    • Localized
    • Pruriginosa
    • Self-improving
  • Dominant DEB (DDEB)
    • Intermediate
    • Localized
    • Pruriginosa
    • Self-improving
  • Compound heterozygous DEB 1
    • DEB, severe

For synonyms and outdated names see Nomenclature.

1.

Individuals with one COL7A1 pathogenic variant associated with DDEB and a second COL7A1 pathogenic variant associated with RDEB

Diagnosis

Suggestive Findings

Dystrophic epidermolysis bullosa (DEB) should be suspected in individuals with the following clinical findings:

  • Fragility of the skin, manifested by blistering with minimal trauma that heals with milia and scarring
  • Absent lingual papillae
  • Blistering and erosions that may:
    • Lead to aplasia cutis congenita at birth (absence of skin, especially on extremities; noted in all types of epidermolysis bullosa);
    • Be present in the neonatal period;
    • Affect the whole body, including mucous membranes (most severe forms), or primarily the hands, feet, knees, and elbows (milder forms);
    • Lead to pseudosyndactyly of the hands and feet (severe forms);
    • Lead to oral and/or esophageal scarring and strictures;
    • Lead to corneal erosions, scarring, and loss of vision;
    • Predispose to squamous cell carcinoma.
  • Dystrophic or absent nails, especially toenails

Family history is consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity) or autosomal dominant inheritance (e.g., affected males and females in multiple generations). Absence of a known family history does not preclude the diagnosis.

Establishing the Diagnosis

The diagnosis of DEB is established in a proband with suggestive findings and one of the following:

Note: (1) Molecular genetic testing is the preferred diagnostic method [Phillips et al 2022]; skin biopsy for diagnostic purposes should only be considered if molecular results are inconclusive or molecular testing is not available. (2) Per ACMG/AMP variant interpretation guidelines, the terms "pathogenic variant" and "likely pathogenic variant" are synonymous in a clinical setting, meaning that both are considered diagnostic and can be used for clinical decision making [Richards et al 2015]. Reference to "pathogenic variants" in this GeneReview is understood to include likely pathogenic variants. (3) Identification of a heterozygous or biallelic variants of uncertain significance does not establish or rule out the diagnosis.

Molecular Genetic Testing

Molecular testing approaches can include a combination of gene-targeted testing (multigene panel, single-gene testing) and comprehensive genomic testing (exome sequencing, genome sequencing). Gene-targeted testing requires that the clinician determine which gene(s) are likely involved (see Option 1), whereas comprehensive genomic testing does not (see Option 2).

Option 1

An epidermolysis bullosa multigene panel that includes COL7A1 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition while limiting identification of pathogenic variants and variants of uncertain significance in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.

For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.

Single-gene testing. Sequence analysis of COL7A1 is performed first to detect missense, nonsense, and splice site variants and small intragenic deletions/insertions. Note: (1) Depending on the sequencing method used, single-exon, multiexon, or whole-gene deletions/duplications may not be detected. If no variant is detected by the sequencing method used, the next step is to perform gene-targeted deletion/duplication analysis to detect exon and whole-gene deletions or duplications. (2) DEB may be difficult to distinguish from other types of epidermolysis bullosa, especially in infants. Therefore, a multigene panel is often considered as a first-tier test.

Option 2

When the phenotype is indistinguishable from many other inherited disorders characterized by epidermolysis bullosa, comprehensive genomic testing does not require the clinician to determine which gene is likely involved. Exome sequencing is most commonly used; genome sequencing is also possible.

For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.

Table 1.

Molecular Genetic Testing Used in Dystrophic Epidermolysis Bullosa

Gene 1MethodProportion of Pathogenic Variants 2 Identified by Method
COL7A1 3Sequence analysis 495% 5
Gene-targeted deletion/duplication analysis 6<2% 7
1.
2.

See Molecular Genetics for information on variants detected in this gene.

3.

Some pathogenic variants in COL7A1 have been described in both recessive and dominant inheritance patterns [Almaani et al 2011]. If two variants in COL7A1 are found, parental testing should be performed to establish that the variants are biallelic.

4.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

5.

Pathogenic variant detection rate by sequence analysis in individuals with biopsy-diagnosed DEB is 95% [Kern et al 2006, Bale & Pfendner 2014, Pfendner et al 2017].

6.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

7.

Proportion of pathogenic variants identified by gene-targeted deletion/duplication analysis is <1% for dominant DEB and <2% for recessive DEB [Pfendner et al 2017].

Skin Biopsy

Examination of a skin biopsy by transmission electron microscopy (TEM) and/or immunofluorescent antibody/antigen mapping is sometimes performed to establish the diagnosis of DEB, although molecular genetic testing is preferred.

If skin biopsy for immunofluorescent mapping is pursued, a punch or shave biopsy that includes the full basement membrane zone should be performed. The biopsy should be taken from the leading edge of a fresh (<12 hours old) blister or from a mechanically induced blister (with a pencil eraser rubbed on the skin). Older blisters undergo change that may obscure the diagnostic morphology.

Light microscopy is INADEQUATE AND UNACCEPTABLE for the accurate diagnosis of DEB.

TEM

  • TEM is used to examine the number and morphology of the basement membrane zone structures – in particular, the presence and morphology of anchoring fibrils. TEM shows the condition of anchoring fibrils, as well as anchoring filaments and keratin intermediate filaments important in other types of epidermolysis bullosa. TEM allows examination of microvesicles that show the tissue cleavage plane that is below the basement membrane in DEB.
  • Specimens must be placed in a special fixation medium (e.g., glutaraldehyde) as designated by the laboratory performing the test.
  • Formaldehyde-fixed samples CANNOT be used for TEM.

Findings on TEM in DEB include the following:

  • All DEB. Cleavage is observed below the lamina densa of the basement membrane zone.
  • Severe RDEB. Anchoring fibrils are absent, markedly reduced, or abnormal in morphology.
  • DDEB, severe RDEB, and intermediate RDEB
    • Anchoring fibrils may appear reduced in number and/or show altered morphology.
    • Intracellular retention of collagen VII can be observed in some individuals.

Findings with immunofluorescent microscopy include the following:

  • Staining of collagen VII using antibodies is diminished or absent.
  • In milder forms of RDEB and in DDEB, staining for collagen VII may appear normal, but cleavage planes are below the lamina densa.
  • Normal staining for other antigens (e.g., laminin 332, collagen XVII, plectin, α6β4 integrin, and keratins 5 and 14) helps to confirm the diagnosis of DEB.
  • Caution: Specimens must be sent to a laboratory that has the appropriate antibodies to detect COL7A1. Routine immunofluorescence only screens for autoantibodies.
  • Especially in milder forms of DEB, immunofluorescent studies are often not sufficient to make the diagnosis because near-normal COL7A1 levels are detected, and no cleavage plane is observed.

Clinical Characteristics

Clinical Description

Dystrophic epidermolysis bullosa (DEB) is characterized by increased skin fragility and dystrophic or absent nails; features are usually present at birth (see Figure 1). 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 clinical subtypes based on severity.

Figure 1.

Figure 1.

Common findings of dystrophic epidermolysis bullosa (DEB) a, b. Scarring on knees and hands and dystrophic nails found in dominant DEB in an adult

Table 2.

Dystrophic Epidermolysis Bullosa: Frequent Features of the Most Common Subtypes

Clinical FeaturesDEB Subtype
Severe recessiveIntermediate recessiveIntermediate dominantLocalized dominant
Age of onset BirthBirth or infancyBirth, infancy, or childhoodBirth, infancy, childhood, or adulthood
Blisters YesYesYesRare, primarily on feet
Nail involvement YesYesYesYes
Esophageal strictures YesRarelyVery rarelyVery rarely
Absent lingual papillae 1 YesYesNoNo

DEB = dystrophic epidermolysis bullosa

1.

Recessive DEB (RDEB) Phenotypes

Severe RDEB

In severe RDEB, blisters are present at birth or become apparent in the neonatal period. Aplasia cutis congenita, especially of the extremities, may be found in the newborn period. Blisters can affect the whole body, including the skin, oral mucosa, esophageal mucosa, and corneas, as early as the newborn period. Chronic non-healing wounds and secondary infection are common, often with Staphylococcus, Pseudomonas, and Streptococcus. Many individuals develop large, irregular brown patches that histologically comprise collections of nevus cells and are called epidermolysis bullosa (EB) nevi [Lanschuetzer et al 2010]. No instances of melanoma arising in these nevi have been reported to date.

Squamous cell carcinoma (SCC). The lifetime risk of SCC is greater than 90% with significant metastatic potential [Fine et al 2009]. SCC usually appears in the third decade but can appear as early as the second decade [Ayman et al 2002]. Affected individuals often succumb to aggressive metastatic SCC [Mellerio et al 2016, Bonamonte et al 2022, Hwang et al 2024]. Satisfactory treatment is currently not available.

Oral involvement may lead to fusion of the tongue to the floor of the mouth (ankyloglossia), progressive diminution of the size of the oral cavity and mouth opening (microstomia), and poor dental hygiene and caries [Krämer et al 2012]. Individuals with RDEB lack lingual papillae [Krämer et al 2020].

Gastrointestinal. Esophageal blisters and erosions as well as webs and strictures can cause severe dysphagia [Azizkhan et al 2006, Mortell & Azizkhan 2010], and strictures can require dilation [Pope et al 2020]. Rarely, affected individuals can have esophageal disease with few or no skin manifestations. Gastroesophageal reflux disease is also common. Anal erosions, poor intake of fluid and fiber, and use of opioid analgesics contribute to frequent severe constipation.

Malnutrition caused by poor intake and an increased nutritional demand for tissue healing can result in growth restriction in young children and absent or delayed puberty in older children. Osteopenia/osteoporosis are not uncommon. Vitamin and mineral deficiencies can occur, especially with iron, zinc, carnitine, selenium, vitamin A, and vitamin D [Haynes 2010].

Anemia results from poor iron intake and/or absorption of iron as well as anemia of chronic disease with bone marrow suppression [Liy-Wong et al 2023, Tarango et al 2023].

Ocular. Corneal erosions can lead to scarring and loss of vision [Matsumoto et al 2005].

Cardiac. Dilated cardiomyopathy, sometimes associated with selenium and carnitine deficiency, has been reported in RDEB and can be fatal in some individuals [Lara-Corrales et al 2010, Ryan et al 2016].

Urologic / kidney function. Rarely, urethral erosions, strictures, bladder dysfunction, and glomerulonephritis can occur, sometimes leading to kidney failure [Fine et al 2004, Hughley et al 2020].

Orthopedic. Individuals with RDEB can develop contractures and pseudosyndactyly (fusion) of the fingers with consequent impairment of function and decreased quality of life [Eismann et al 2014]. Although fusion of the toes is not detrimental to function, painful blistering and progressive contractures of the foot and ankle as well as the larger joints (knees, hips, neck) can interfere with ambulation and function.

Endocrine. Delayed puberty is not uncommon and is often associated with osteopenia, osteoporosis, and vitamin D deficiency [Wasserman et al 2023]. Poor bone health results from poor nutrition, lack of exposure to adequate sunlight, and inactivity [Martinez & Mellerio 2010, Rodari et al 2017].

Psychosocial. Severe stress may affect the affected individual and family because of the complications of this disorder and the chronic pain endured by most individuals with EB. Quality of life can be decreased, and psychosocial disorders including anxiety, depression, and drug dependence/abuse may occur in older persons [Frew & Murrell 2010] – although a recent study showed that pain in individuals with DEB is not correlated with anxiety or depression [Fortuna et al 2016].

Intermediate RDEB

Intermediate RDEB may be mild, with blistering localized to hands, feet, knees, and elbows as well as dystrophic nails, or relatively more widespread including flexural areas and trunk. Scarring, milia, and nevi are present but without the severe, mutilating scarring seen in severe RDEB. Onset of blistering ranges from birth to childhood depending on type. Pseudosyndactyly, damaged or absent nails, and oral lesions may occur. Growth deficiency is possible but not as severe as with severe RDEB. SCC also develops in some affected individuals.

Inversa RDEB

Inversa RDEB is a rare phenotype. Blistering and skin atrophy occurs on the flexural areas of the breasts, neck, thighs, and legs while few changes are observed on the hands, feet, elbows, or knees. Otherwise, the phenotype resembles DEB types with blistering and resulting scarring. Blisters of the hands and feet may be present in infancy.

Localized RDEB

Localized RDEB is a rare phenotype that exhibits blistering with scarring that may be severe but is localized to the hands and feet. Other sites are not affected. The nails are often absent. Growth restriction and systemic illness are also absent. SCC has not been reported in individuals who have this subtype.

Pruriginosa RDEB

Pruriginosa RDEB often affects the shins. Pretibial blisters develop into prurigo-like hyperkeratotic lesions. The lesions occur predominantly on the pretibial areas, sparing the knees and other parts of the skin. Other findings include nail dystrophy, small, white scars (albopapuloid skin lesions), and hypertrophic scars without pretibial predominance.

Self-improving RDEB

Bullous dermolysis of the newborn often has only transient blistering limited to the newborn period [Fassihi et al 2005]. Molecular genetic testing of these individuals rarely reveals biallelic COL7A1 pathogenic variants [Frew et al 2011, Boccaletti et al 2015, Diociaiuti et al 2016].

Dominant DEB (DDEB) Phenotypes

In this milder form of DEB, blistering is often limited to the hands, feet, knees, and elbows. Blistering may be relatively benign but nonetheless heals with scarring. Dystrophic nails, especially toenails, are common, and loss of nails may occur. In the mildest forms, dystrophic nails may be the only finding. Blistering in DDEB often improves somewhat with age, possibly as a result of reduced physical activity. The subtypes of DDEB resemble those of RDEB but may present with milder manifestations. There may be significant clinical variability among affected family members.

Intermediate DDEB

Intermediate DDEB is a milder form of DEB than RDEB. Generalized blistering affects most sites of friction in infancy but often evolves to less severe disease in adulthood. Blisters form with scarring, and the nails are often absent. Other systems are generally unaffected, and growth deficiency and SCC are rarely reported.

Localized DDEB

Localized DDEB includes pruriginosa DDEB as well as acral and nails-only types. Nails-only localized DDEB affects the nails, which are dystrophic and fragile. Other family members, however, may have more severe manifestations.

Pruriginosa DDEB

This rare subtype affects the anterior lower legs primarily and is characterized by intense pruritus. In some instances, there is prurigo nodularis.

Self-improving DDEB

This is the more common dominant form of bullous dermolysis of the newborn. Individuals often have only transient blistering limited to the newborn period [Fassihi et al 2005]. Molecular genetic testing of these individuals most often reveals heterozygous COL7A1 pathogenic variants [Frew et al 2011, Boccaletti et al 2015, Diociaiuti et al 2016].

Compound Heterozygous DEB

Individuals with one COL7A1 pathogenic variant associated with DDEB and a second COL7A1 pathogenic variant associated with RDEB can have clinical manifestations that range from mild to severe depending on the type of COL7A1 pathogenic variant associated with RDEB, but most have clinical features that resemble RDEB [Has et al 2020].

Genotype-Phenotype Correlations

RDEB

  • Severe RDEB is typically caused by biallelic pathogenic variants in COL7A1 that result in null or out-of-frame insertions/deletions, and splice site variants resulting in little to no functional protein. Recent analysis of 236 individuals with RDEB showed correlation with types of pathogenic variants and disease severity: individuals with loss-of-function variants had more significant cutaneous and extracutaneous symptoms [Pathmarajah et al 2025].
  • Intermediate RDEB and less severe forms generally result from having at least one variant that allows for partially functional protein. This could include missense variants for both alleles, or one allele with a missense variant and the other with a higher-impact variant such as a splice site or other variant resulting in little to no functional protein [Chen et al 2023, So et al 2024, Pathmarajah et al 2025].

DDEB. Most DDEB results from dominant-negative amino acid substitutions of glycine in the collagenous triple helical domain of collagen VII, especially in exons 73, 74, and 75. The most common variants of these are p.Gly2043Arg and p.Gly2043Glu [Has et al 2020, Chen et al 2023]. Of note, a few splice site variants and other amino acid substitutions have been reported. Inter- and intrafamilial clinical variability has been reported [Natale et al 2022, Chen et al 2023].

See also Table 9 and Pathmarajah et al [2025].

Penetrance

Penetrance for DDEB is reduced; unaffected individuals have been identified [Almaani et al 2011].

Nomenclature

The nomenclature for DEB has changed five times in the last 20 years. A classification system was developed in 2014, referred to as the "onion skin" terminology, which considers the level of blistering, phenotypic characteristics including distribution and severity of cutaneous blisters and wounding, and associated gene [Fine et al 2014].

The most recent reclassification system for DEB and other skin fragility disorders was published following the 2019 international consensus meeting [Has et al 2020] (see Table 3). Further revisions in classification can be expected.

Table 3.

Comparison of Dystrophic Epidermolysis Bullosa Classifications for Major Subtypes

Original Designation2008 Nomenclature2014 Nomenclature 12020 Nomenclature 2
Hallopeau-Siemens type (RDEB-HS)RDEB, severe generalizedRDEB generalized severeSevere RDEB
Rare: Inversa RDEB, pruriginosa RDEB, & localized RDEB
Non-Hallopeau-Siemens type (RDEB-non-HS)RDEB, generalized otherRDEB generalized intermediateIntermediate RDEB
--DDEB generalizedDDEB generalizedIntermediate DDEB
Rare: Pruriginosa DDEB & self-improving DDEB
--DDEB, nails only, pretibial, & acralDDEB localizedLocalized DDEB
------Compound heterozygous DEB 3

DDEB = dominant dystrophic epidermolysis bullosa; RDEB = recessive dystrophic epidermolysis bullosa

1.
2.
3.

Individuals with one COL7A1 pathogenic variant associated with DDEB and a second COL7A1 pathogenic variant associated with RDEB

Prevalence

According to the National EB Registry, the overall prevalence of EB is 11.07 in one million live births [Fine 2016]. The prevalence of DDEB and RDEB, respectively, is 1.49 and 1.35 in one million live births.

The carrier frequency of RDEB in the US population has been estimated at one in 370 [Pfendner et al 2001].

Differential Diagnosis

Blistering, especially in the neonatal period, should prompt consideration of acquired conditions and congenital genetic disorders.

  • Acquired conditions. It is important to rule out bacterial (bullous impetigo and staphylococcal scalded skin syndrome) and viral infections (primarily herpes simplex infections). Rarely, autoimmune blistering conditions may present in the neonatal period, especially if the mother has a history of similar conditions.
  • Congenital genetic disorders. Other skin fragility entities such as keratinopathic ichthyoses (associated with pathogenic variants in KRT1, KRT10, or KRT2 [OMIM PS113800]), peeling skin disorders, erosive skin fragility disorders, and connective tissue disorders with skin fragility should be considered [Has et al 2020]. Rarely, congenital erythropoietic porphyria and diffuse cutaneous mastocytosis (OMIM 154800) may also present with diffuse blistering.

Although clinical examination is useful in determining the extent of blistering and the presence of oral and other mucous membrane lesions, defining characteristics such as the presence and extent of scarring – especially in young children and neonates – may not be established or significant enough to allow identification of EB type or subtype. Thus, molecular genetic testing (or less commonly skin biopsy) is required to establish the most precise diagnosis.

Table 4.

Genes Associated with the Four Major Epidermolysis Bullosa Types

GeneEB TypeMOI
COL7A1 DEB AD, AR
CD151 EBS AR
DST EBS AR
EXPH5 EBS AR
KLHL24 EBS AD
KRT5 EBS AR, AD
KRT14 EBS AR, AD
PLEC EBS AR, AD
COL17A1 JEB AR
ITGA3 JEB AR
ITGA6 JEB AR
ITGB4 JEB AR
LAMA3 JEB AR
LAMB3 JEB AR
LAMC2 JEB AR
FERMT1 Kindler EB AR

Adapted from Has et al [2020], Table 1

AD = autosomal dominant; AR = autosomal recessive; DEB = dystrophic epidermolysis bullosa; EB = epidermolysis bullosa; EBS = epidermolysis bullosasimplex; JEB = junctional epidermolysis bullosa; MOI = mode of inheritance

Management

International clinical practice guidelines for dystrophic epidermolysis bullosa (DEB) have been published by DEBRA International. These include guidelines for treatment of anemia, foot care, occupational therapy, palliative and end-of-life care, psychosocial care, neonatal care, cancer management, hand surgery and hand therapy, oral health care, physical therapy, skin and wound care, constipation management, pain care, pregnancy, childbirth, and aftercare, and supporting sexuality.

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with DEB, the evaluations summarized in Table 5 (if not performed as part of the evaluation that led to the diagnosis) are recommended.

Table 5.

Dystrophic Epidermolysis Bullosa: Recommended Evaluations Following Initial Diagnosis

System/ConcernEvaluationComment
Skin
  • Thorough eval of skin surface for blisters, erosions, & infections
  • Eval of crusted, non-healing, or painful lesions in older persons for SCC
Difficult for some persons to fully undress in clinic; may need to rely on photos
Oral mucosa
  • Dental consult
  • Exam of mouth incl mucosal blistering & erosions
  • Assessment for dental caries & crowding
Gastrointestinal
  • Gastroenterology consult
  • Barium swallow for esophageal strictures if there are symptoms of dysphagia
  • Assessment for GERD & constipation
Nutrition/Growth
  • Measurement of height, weight, & BMI
  • Eval of nutritional status & need for gastrostomy feeding
  • Assessment for vitamin & mineral deficiency incl anemia (serum selenium, carnitine, zinc, 25- hydroxyvitamin D3 levels; CBC & iron studies)
Anemia CBC & iron studies incl sTfR/log ferritinHematology consult as needed in those w/anemia 2
Ocular Exam by ophthalmologist to evaluate for corneal abrasions & scars
Cardiac Echocardiogram & EKGReferral to cardiologist if needed
Urologic / Kidney function
  • Urinalysis to assess for hematuria & proteinuria
  • Assessment for urinary symptoms or abnormal renal tests (BUN, creatinine, cystatin C)
Referral to urologist or nephrologist if needed
Orthopedic
  • Eval of hand function & mobility/dexterity status by PT or OT
  • Assessment of footwear & mobility issues
  • Spine radiographs & DXA scan for osteoporosis beginning at age 8 yrs
Referral to hand surgeon as needed in those w/hand involvement
Endocrine Eval of pubertal status beginning at age 6-8 yrs
Psychosocial
  • Eval by professional to assess for anxiety, depression, & substance dependency/abuse (preferably by psychologist on EB team)
  • Assistance w/school-related issues
  • Assistance w/access to needed services, insurance, & disability accommodations
Genetic counseling By genetics professionals 2To obtain a pedigree & inform affected persons & their families re nature, MOI, & implications of DEB to facilitate medical & personal decision making

BUN = blood urea nitrogen; CBC = complete blood count; DEB = dystrophic epidermolysis bullosa; DXA = dual-energy x-ray absorptiometry; EB = epidermolysis bullosa; GERD = gastroesophageal reflux disease; MOI = mode of inheritance; OT = occupational therapist; PT = physical therapist; SCC = squamous cell carcinoma; sTfR = soluble transferrin receptor

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Clinical geneticist, certified genetic counselor, certified genetic nurse, genetics advanced practice provider (nurse practitioner or physician assistant)

Treatment of Manifestations

Targeted Therapies

In GeneReviews, a targeted therapy is one that addresses the specific underlying mechanism of disease causation (regardless of whether the therapy is significantly efficacious for one or more manifestation of the genetic condition); would otherwise not be considered without knowledge of the underlying genetic cause of the condition; or could lead to a cure. —ED

Table 6.

Dystrophic Epidermolysis Bullosa: Targeted Therapies

Treatment ClassMechanism of ActionSpecific DrugsDoseComments
Gene therapyCOL7A1 replacementBeremagene geperpavec-svdt
(Vyjuvek®)
Topical, 1x/week
  • FDA approved for wound treatment in those age ≥6 mos w/molecularly confirmed DEB
  • Weekly maximum dose by age
Botanical drug productUnknown; may stimulate keratinocyte growth &/or ↑ collagen productionBirch triterpenes / birch bark extract (Filsuvez®)Topical, 2x/daily
  • EMA & FDA approved for wound treatment in those age ≥6 mos w/EB [Danescu et al 2024]
  • Also ↓ inflammation & ↑ blood flow

DEB = dystrophic epidermolysis bullosa; EB = epidermolysis bullosa; EMA = European Medicines Agency; FDA = US Food and Drug Administration

Supportive Care

Supportive care to improve quality of life, maximize function, and reduce complications is recommended. This ideally involves multidisciplinary care by specialists in relevant fields (see Table 7).

Table 7.

Dystrophic Epidermolysis Bullosa: Treatment of Manifestations

Manifestation/ConcernTreatmentConsiderations/Other
Skin Minimize new blister formation by:
  • Teaching caretakers proper handling of infants & children to protect skin from shearing forces;
  • Wrapping & padding extremities;
  • Use of soft & properly fitted clothing & footwear.
  • Vaginal delivery is preferred, but in certain circumstances, cesarean delivery may be recommended to ↓ skin trauma in affected fetus. 1
  • Encourage age-appropriate play involving activities that cause minimal trauma to skin.
  • Use dressings & padding to protect bony prominences from blister-inducing impact.
New blisters should be lanced & drained to prevent further spread from fluid pressure. Dressings for blisters typically involve 3 layers: 2
  • A primary nonadherent contact layer that does not strip top layers of epidermis. Tolerance to different primary layers varies. Primary layers incl: dressings impregnated w/emollient (e.g., petrolatum, topical antiseptic); nonstick products (e.g., Telfa®, N-Terface®); silicone-based products w/o adhesive (e.g., Mepitel®, Mepilex®); additional topical antibiotic or antiseptic (e.g., bacitracin, mupirocin, silver, honey).
  • A secondary layer that provides stability for primary layer & adds padding to allow more activity, such as rolls of gauze (e.g., Kerlix®, Conform®)
  • An elastic mesh-like tertiary layer that ensures integrity of dressing (e.g., burn net, Coban®, or elasticized tube gauze of varying diameters such as BandNet® or Tubifast®)
Non-healing wounds may require coverage w/biologic skin substitutes or temporary porcine or human cadaver skin grafts (see Therapies Under Investigation).
  • Treatment of wound infection using antibiotics & antiseptics
  • Appropriate footwear & PT are essential to preserve ambulation in children w/delays or difficulty walking due to blistering &/or hyperkeratosis.
Pain/Itch A variety of topical, oral, & psychological therapies have been advocated.
Squamous cell carcinoma A variety of approaches to treatment of SCC have been summarized. 3There is no well-accepted standard of care.
Oral
  • Good dental care & frequent exams to ensure adequate caloric intake
  • Extractions for dental caries & crowding as needed
Gastrointestinal
  • Esophageal strictures & webs can be dilated repeatedly to improve swallowing.
  • Mgmt of constipation
Nutrition
  • Fluid electrolyte mgmt in neonatal period & in infants w/widespread disease
  • Nutrition support as needed incl feeding gastrostomy tube to assure adequate caloric intake
  • Vitamin A & zinc replacement when levels are low to improve corneal stability & enhance wound healing
  • Selenium & carnitine replacement when levels are low to possibly prevent dilated cardiomyopathy
Anemia Treatment w/oral iron supplements, intravenous iron infusions, &/or red blood cell transfusions
Ocular Prophylactic use of eye lubricants &, in some persons, protective contact lenses may prevent corneal abrasions.
Cardiac Refer to cardiologist if dilated cardiomyopathy is detected on echocardiogram.Treatment w/beta-blockers &/or ACE inhibitors may be able to control or reverse cardiomyopathy.
Urologic / Kidney function
  • Refer to urologist for urethral erosions, strictures, or bladder dysfunction.
  • Refer to nephrologist for hematuria or proteinuria to assess for glomerulonephritis & kidney failure.
Orthopedic OT may help prevent progressive hand contractures.Splinting of hands can be problematic because of skin fragility.
Surgical release of fingers; may need to be performed repeatedly.Some centers advocate preservation of functional thumb in preference to whole-hand releases.
  • Calcium & vitamin D supplementation as needed
  • Intravenous bisphosphonates for osteopenia/osteoporosis
Endocrine/
Gynecologic
  • Estrogen replacement as needed for those w/delayed puberty
  • Menstrual periods can be suppressed to prevent exacerbation of anemia.
Psychosocial Psychosocial support incl social services & psychological counseling for affected persons & their families

ACE = angiotensin-converting enzyme; DEB = dystrophic epidermolysis bullosa; OT = occupational therapy; PT = physical therapy; SCC = squamous cell carcinoma

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Surveillance

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in Table 8 are recommended.

Table 8.

Dystrophic Epidermolysis Bullosa: Recommended Surveillance

System/ConcernEvaluationFrequency
Skin Thorough eval of skin surface for blisters, erosions, & infectionsAt each visit & per dermatologist
  • Eval of crusted, non-healing, painful, abnormal-looking lesions or those w/exuberant scar tissue for risk of SCC
  • Frequent biopsies of suspicious lesions may be necessary followed by local excision.
  • At least annually beginning at age ≥10 yrs
  • Note: Affected persons are often unwilling to undress completely in clinic setting & home photographs during dressing changes may have to suffice.
Oral mucosa Assessment of oral mucosa, feeding, & esophageal involvementAt each visit
Dental Dental eval for dental caries & crowdingEvery 6 mos
Gastrointestinal Assessment for GERD & constipationAt each visit
Barium swallow for esophageal stricturesIf there are symptoms of dysphagia
Nutrition/Growth
  • Measurement of height, weight, & BMI
  • Eval of nutritional status
At each visit
  • Serum vitamin A, selenium, carnitine, & zinc levels
  • Serum 25-hydroxyvitamin D3
Every 6-12 mos
Anemia
  • CBC
  • Iron studies
Every 6-12 mos
Ocular Ophthalmologic exam to evaluate for corneal abrasions & scarsAs needed
Cardiac Echocardiogram to assess for cardiomyopathyAnnually starting by age 2 yrs for those w/severe disease
Urologic / Kidney function Urinalysis to assess for hematuria & proteinuriaEvery 6-12 mos to evaluate for kidney function & for cystitis
Orthopedic
  • Eval of hand function & mobility/dexterity status by PT or OT
  • Assessment of footwear & mobility issues
At each visit or as needed
Spine radiographs & DXA scan to assess for osteoporosisAnnually starting by age 6 yrs or earlier in those w/unexplained pain &/or spontaneous fractures
Endocrine Eval of pubertal statusAt each visit beginning at age 10-12 yrs
Liver Liver function testsEvery 6-12 mos to evaluate for liver function 1
Psychosocial Assessment of family needsAt each visit or as needed

DXA = dual-energy x-ray absorptiometry; GERD = gastroesophageal reflux disease; OT = occupational therapy; PT = physical therapy; SCC = squamous cell carcinoma

1.

Rarely, individuals with recessive DEB (RDEB) can develop fulminant and even fatal hepatic failure. Some of the medications used in severe RDEB for pain, itch, and/or infection may have adverse effects on liver function.

Agents/Circumstances to Avoid

Nasogastric tubes are discouraged because of oral and esophageal fragility [Bageta et al 2024].

Poorly fitting or coarse-textured clothing and footwear should be avoided, as they can cause trauma.

In general, activities that traumatize the skin (e.g., hiking, mountain biking, contact sports) should be avoided; affected individuals who are committed to participation in such activities should be encouraged to devise ways of protecting the skin.

Most persons with DEB cannot tolerate the use of ordinary medical tape or Band-Aids®.

Evaluation of Relatives at Risk

Evaluation of an at-risk newborn for evidence of blistering is appropriate so that trauma to the skin can be avoided as much as possible.

Given the significant clinical variability that may be seen among family members with DEB, it is appropriate to clarify the genetic status of apparently asymptomatic older and younger at-risk relatives of an affected individual by molecular genetic testing of the COL7A1 pathogenic variant(s) in the family in order to identify as early as possible those who would benefit from prompt initiation of treatment and preventive measures.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Pregnancy Management

Data on pregnancy and DEB are limited, but a recent survey did not detect increased risk for pregnancy-related complications in women with various forms of epidermolysis bullosa [Intong et al 2017, Greenblatt et al 2022].

Therapies Under Investigation

There are several promising therapies currently being studied, including genetically corrected autologous epidermal grafts [Siprashvili et al 2016] and various stem cell therapies including bone marrow transplant, mesenchymal stem cells, stromal cells, induced pluripotent stem (IPS) cells [Tamai & Uitto 2016], and gene-corrected fibroblasts [Jacków et al 2016]. Stop codon read-through, exon skipping, COL7A1 protein therapy, and revertant mosaicism are being investigated.

A clinical trial has shown the efficacy of autologous transgenic keratinocyte cultures used to regenerate an entire, fully functional epidermis on a child age seven years suffering from severe JEB [Hirsch et al 2017]. Similar studies are under way for DEB [Siprashvili et al 2016, So et al 2022] and awaiting FDA approval.

There are many new approaches to therapy currently in trial. Clinical trials evaluating antifibrotic, anti-inflammatory, and antipruritic medications are in progress [Danescu et al 2024].

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, mode(s) of inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members; it is not meant to address all personal, cultural, or ethical issues that may arise or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Dystrophic epidermolysis bullosa (DEB) is inherited in an autosomal recessive (RDEB) or autosomal dominant (DDEB) manner. Some COL7A1 pathogenic variants are associated with both DDEB and RDEB.

Determining the mode of inheritance in a simplex case (i.e., a single occurrence in a family). Molecular characterization of the COL7A1 pathogenic variants is the only accurate method of determining mode of inheritance and recurrence risk. Multiple individuals with one COL7A1 pathogenic variant associated with DDEB and a second COL7A1 pathogenic variant associated with RDEB (compound heterozygous DEB) have been reported, suggesting caution when predicting recurrence risk based on parental phenotype alone (i.e., without molecular genetic testing) [Varki et al 2007, Turczynski et al 2016].

Phenotypic severity and transmission electron microscopy (TEM) and/or immunofluorescent antibody/antigen mapping findings alone are not sufficient to determine mode of inheritance and recurrence risk, as phenotypic variability is extreme in RDEB. An individual with a mild phenotype and no family history may have either autosomal dominant or autosomal recessive DEB; numerous descriptions of the spectrum of phenotypes in RDEB document that some are very mild and mimic DDEB.

Autosomal Dominant Inheritance – Risk to Family Members

Parents of a proband

  • Approximately 70% of individuals diagnosed with DDEB are reported to have an affected parent.
  • About 30% of individuals diagnosed with DDEB may have the disorder as the result of a de novo COL7A1 pathogenic variant [Chen et al 2023]; however, these numbers may not reflect the true proportion of de novo pathogenic variants because of ascertainment bias. Note: A proband may appear to be the only affected family member because of failure to recognize the disorder in family members or reduced penetrance. Therefore, de novo occurrence of a COL7A1 pathogenic variant in the proband cannot be confirmed unless molecular genetic testing has demonstrated that neither parent has the COL7A1 pathogenic variant.
  • If the proband appears to be the only affected family member, molecular genetic testing is recommended for the parents of the proband to evaluate their genetic status and inform recurrence risk assessment.
  • If the pathogenic variant identified in the proband is not identified in either parent and parental identity testing has confirmed biological maternity and paternity, the following possibilities should be considered:

Sibs of a proband. The risk to the sibs of the proband depends on the genetic status of the proband's parents:

Offspring of a proband. Each child of an individual with DDEB has a 50% chance of inheriting the COL7A1 pathogenic variant.

Other family members. The risk to other family members depends on the status of the proband's parents: if a parent has the COL7A1 pathogenic variant, the parent's family members may be at risk.

Autosomal Recessive Inheritance – Risk to Family Members

Parents of a proband

Sibs of a proband

  • If both parents are known to be heterozygous for a COL7A1 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being heterozygous, and a 25% chance of inheriting neither of the familial pathogenic variants.
  • Heterozygous sibs of a proband with RDEB are typically asymptomatic.

Offspring of a proband. The offspring of an individual with RDEB are obligate heterozygotes for a pathogenic variant in COL7A1.

Other family members. Each sib of the proband's parents is at a 50% risk of being heterozygous for a COL7A1 pathogenic variant.

Heterozygote detection. Heterozygote testing for at-risk relatives requires prior identification of the COL7A1 pathogenic variants in the family.

Related Genetic Counseling Issues

See Management, Evaluation of Relatives at Risk for information on evaluating at-risk relatives for the purpose of early diagnosis and treatment.

Family planning

  • The optimal time for determination of genetic risk and discussion of the availability of prenatal/preimplantation genetic testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.

DNA banking. Because it is likely that testing methodology and our understanding of genes, pathogenic mechanisms, and diseases will improve in the future, consideration should be given to banking DNA from probands in whom a molecular diagnosis has not been confirmed (i.e., the causative pathogenic mechanism is unknown). For more information, see Huang et al [2022].

Prenatal Testing and Preimplantation Genetic Testing

Once the COL7A1 pathogenic variant(s) have been identified in an affected family member, prenatal and preimplantation genetic testing are possible.

Differences in perspective may exist among medical professionals and within families regarding the use of prenatal and preimplantation genetic testing. While most health care professionals would consider use of prenatal and preimplantation genetic testing to be a personal decision, discussion of these issues may be helpful.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

  • DebRA Chile
    Chile
    Phone: +56 2 22286725
    Email: info@debrachile.cl
  • DEBRA International
  • debra of America
    Phone: 833-debraUS; 833 332-7287
    Email: staff@debra.org
  • DEBRA UK
    United Kingdom
    Phone: 01344 771961
    Email: debra@debra.org.uk
  • Epidermolysis Bullosa Medical Research Foundation
    Phone: 310-205-5119
    Email: a.pett@bep-la.com
  • EB Research Partnership (EBRP)
    Phone: 646-844-0902
    Email: info@ebresearch.org
  • DEB Register
    International registry of dystrophic epidermolysis bullosa (DEB) patients and associated COL7A1 mutations.
  • EBCare Registry
    Email: connect@invitae.com

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

Dystrophic Epidermolysis Bullosa: Genes and Databases

GeneChromosome LocusProteinLocus-Specific DatabasesHGMDClinVar
COL7A1 3p21​.31 Collagen alpha-1(VII) chain COL7A1 database COL7A1 COL7A1

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for Dystrophic Epidermolysis Bullosa (View All in OMIM)

120120COLLAGEN, TYPE VII, ALPHA-1; COL7A1
131705TRANSIENT BULLOUS DERMOLYSIS OF THE NEWBORN; TBDN
131750EPIDERMOLYSIS BULLOSA DYSTROPHICA, AUTOSOMAL DOMINANT; DDEB
131850EPIDERMOLYSIS BULLOSA DYSTROPHICA, PRETIBIAL
132000EPIDERMOLYSIS BULLOSA WITH CONGENITAL LOCALIZED ABSENCE OF SKIN AND DEFORMITY OF NAILS
226600EPIDERMOLYSIS BULLOSA DYSTROPHICA, AUTOSOMAL RECESSIVE; RDEB
226650EPIDERMOLYSIS BULLOSA, JUNCTIONAL 1A, INTERMEDIATE; JEB1A
604129EPIDERMOLYSIS BULLOSA PRURIGINOSA

Molecular Pathogenesis

COL7A1 encodes collagen alpha-1(VII) chain, which is expressed in keratinocytes, including the basal keratinocytes of the epidermis, where the protein product is assembled into homotrimeric molecules with a helical triple collagen domain. The homotrimers then associate via disulfide bonds into homodimeric structures in the extracellular matrix below the lamina densa and form the anchoring fibrils that anchor the basement membrane to the underlying dermis. The anchoring fibrils are linked to the basement membrane through attachment to laminin-5 and the keratinocyte hemidesmosomes directly above. The intracellular keratin intermediate filament network is linked directly to the hemidesmosomes that anchor the keratinocytes to the basal lamina and to the desmosomes that lead to strong attachment of the keratinocytes to one another. These associations along with the network itself supply stability and resistance to stress that enable the keratinocytes to maintain their structural integrity during minor trauma and remain anchored to the basement membrane and dermis [Bruckner-Tuderman 1999].

Pathogenic variants in COL7A1 can lead to reduced resistance to minor trauma and the resulting blistering that is the hallmark of dystrophic epidermolysis bullosa (DEB). The type of pathogenic variant, the biochemical properties of the substituted amino acid, and its location in the protein determine the severity of the blistering phenotype (see Genotype-Phenotype Correlations) and inheritance pattern.

Mechanism of disease causation

  • Recessive DEB (RDEB) usually results from the absence of collagen VII as a result of COL7A1 null variants, although some glycine substitutions and other amino acid substitutions have been described in RDEB.
  • Dominant DEB (DDEB). Glycine substitution variants in the triple helical domain (Gly-X-Y; especially in exons 73, 74, and 75) predominate (>75%) in DDEB and may result in abnormal triple helical coiling and a partially nonfunctional protein product.

Table 9.

COL7A1 Pathogenic Variants Referenced in This GeneReview

Reference SequencesDNA Nucleotide ChangePredicted Protein ChangeComment
NM_000094​.3
NP_000085​.1
c.325_326insCGp.Glu109Alafs39 1RDEB variant prevalent in those of South American ancestry 1
c.7957G>Ap.Gly2653Arg
  • RDEB variant prevalent in those of Argentinian ancestry
  • Phenotype includes mild blistering & severe mucosal involvement 1
c.3625_3635delp.Ser1209fsRecurrent RDEB variant 2
c.8569G>Tp.Glu2857Ter
c.6527dupCp.Gly2177fsRDEB variant prevalent in those of Spanish ancestry 3
c.6127G>Cp.Gly2043ArgRecurrent DDEB variant 2
c.6128G>Ap.Gly2043Glu
c.6205C>Tp.Arg2069CysVariant has been assoc w/inversa RDEB subtype. 4

DDEB = dominant dystrophic epidermolysis bullosa; RDEB = recessive dystrophic epidermolysis bullosa

Variants listed in the table have been provided by the authors. GeneReviews staff have not independently verified the classification of variants.

GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen​.hgvs.org). See Quick Reference for an explanation of nomenclature.

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Chapter Notes

Author Notes

GeneDx website

Cincinnati Children's Epidermolysis Bullosa Center website

Author History

Sarah Crawford, MMSc, CGC (2025-present)
Anne W Lucky, MD (2006-present)
Ellen G Pfendner, PhD; GeneDx, Inc (2006-2025)
Elena Pope, MD, MSc (2025-present)

Revision History

  • 8 May 2025 (sc) Revision: Genotype-Phenotypes Correlations edits
  • 27 March 2025 (sw) Comprehensive update posted live
  • 13 September 2018 (ha) Comprehensive update posted live
  • 26 February 2015 (me) Comprehensive update posted live
  • 4 November 2010 (me) Comprehensive update posted live
  • 21 August 2006 (me) Review posted live
  • 27 December 2005 (ep) Original submission

References

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