Rare Nephrology News

Disease Profile

Dominant dystrophic epidermolysis bullosa

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

US Estimated

Europe Estimated

Age of onset

Infancy

ageofonset-infancy.svg

ICD-10

Q81.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

rnn-autosomaldominant.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

no.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Other names (AKA)

Dominant dystrophic epidermolysis bullosa, generalized; DDEB, generalized; DDEB-gen;

Categories

Congenital and Genetic Diseases; Skin Diseases

Summary

Dominant dystrophic epidermolysis bullosa (DDEB) is a type of epidermolysis bullosa (EB), which is a group of rare inherited conditions in which the skin blisters extremely easily. DDEB is one of the milder forms of EB, although the severity is variable. Blisters may be present at birth, but typically appear during early childhood; occasionally they do not develop until later in life. Blisters often become more numerous and tend to occur over vulnerable sites such as knees, ankles, elbows and knuckles.[1] In adulthood, they usually become less frequent and scars fade. Other signs and symptoms of DDEB may include dystrophic or absent nails,[2] constipation, dental caries and swallowing problems.[1] It is caused by mutations in the COL7A1 gene and is inherited in an autosomal dominant manner.[3] Treatment typically includes treating blisters and avoiding infection.[1]

Symptoms

Dominant dystrophic epidermolysis bullosa (DDEB) is consivered to be a more mild form of dystrophic epidermolysis bullosa (DEB). Blistering is often limited to the hands, feet, knees, and elbows. Blistering may be relatively benign, but still heals with scarring and milia. Dystrophic nails, especially toenails, are common and loss of nails may occur. In the mildest forms, dystrophic nails may be the only characteristic noted. Blistering in DDEB often improves somewhat with age.[4][5]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
30%-79% of people have these symptoms
Acral blistering
0031045
Dystrophic toenail
Poor toenail formation
0001810
Fragile skin
Skin fragility
0001030
Milia
Milk spot
0001056
5%-29% of people have these symptoms
Absent fingernail
0001817
Absent toenail
0001802
Atrophic scars
Sunken or indented skin due to damage
0001075
Dystrophic fingernails
Poor fingernail formation
0008391
Erosion of oral mucosa
0031446
Oral mucosal blisters
Blisters of mouth
0200097
Recurrent loss of toenails and fingernails
Recurrent shedding of toenails and fingernails
0008390
Skin erosion
0200041
Percent of people who have these symptoms is not available through HPO
Abnormal blistering of the skin
Blistering, generalized
Blisters

[ more ]

 0008066
Autosomal dominant inheritance
0000006
Congenital onset
Symptoms present at birth
0003577
Nail dysplasia
Atypical nail growth
0002164
Nail dystrophy
Poor nail formation
0008404
Do you have updated information on this disease? We want to hear from you.

Cause

Dominant dystrophic epidermolysis bullosa (DDEB) is caused by mutations in the COL7A1 gene. The COL7A1 gene provides instructions for making a protein that is used to assemble type VII collagen. Collagen gives structure and strength to connective tissues, such as skin, tendons, and ligaments, throughout the body.

Type VII collagen plays an important role in strengthening and stabilizing the skin. It is the main component of structures called anchoring fibrils, which anchor the top layer of skin, called the epidermis, to an underlying layer called the dermis.

COL7A1 mutations alter the structure or disrupt the production of type VII collagen, which impairs its ability to help connect the epidermis to the dermis. When type VII collagen is abnormal or missing, friction or other minor trauma can cause the two skin layers to separate. This separation leads to the formation of blisters, which can cause extensive scarring as they heal.[6][7]

A diagram of the skin structure including the area of skin implicated in DDEB is provided by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Click on the link for more.

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    There is currently no cure for all types of dystrophic epidermolysis bullosa (DEB). Treatment generally focuses on managing signs and symptoms. For some individuals, such as those that have a mild form of dominant dystrophic epidermolysis bullosa (DDEB), dystrophic nails may be the only manifestation. However, other individuals may have much more severe problems that need to be managed. Management typically focuses on treating blisters and avoiding or treating infections.[4]

    Wound care usually included treatment of new blisters by lancing and draining. Additionally in most cases, wounds are then dressed with a non-adherent material, covered with padding for stability and protection, and secured with an elastic wrap for integrity. Due to the increased risk of bacterial resistance, topical antibiotic ointments and antimicrobial dressings should be reserved for those wounds that are colonized with bacteria and fail to heal, referred to as “critical colonization."[4][5]

    Individuals with epidermolysis bullosa (EB) have increased caloric and protein needs due to the increased energy utilized in wound healing. Involvement of the digestive system in some forms of EB may limit nutritional intake. Infants and children with more severe forms of EB and failure to thrive usually require attention to fluid and electrolyte balance and may require nutritional support, including a gastrotomy feeding tube. Anemia is typically treated with iron supplements and transfusions as needed. Other nutritional supplements may include calcium, vitamin D, selenium, carnitine, and zinc.[4][5]

    Surveillance is important for individuals with DEB. Biopsies of abnormal-appearing wounds that do not heal may be recommended in some types of DEB due to predisposition to squamous cell carcinoma, beginning in the second decade of life. Screening for deficiencies of iron, zinc, vitamin D, selenium, and carnitine is typically recommended after the first year of life. Routine echocardiograms are recommended to identify dilated cardiomyopathy, and bone mineral density studies are recommended to identify osteoporosis. Activities and bandages that may traumatize the skin (including all adhesives) should typically be avoided.[4]

    Recent treatment advancements and therapies under investigation include but are not limited to[4][5][9]: 

    • Use of biological dressings to treat chronic or recurrent skin ulcers
    • Bone marrow transplantation
    • Intra-dermal (in the skin) injection of fibroblasts
    • Protein replacement therapy (intra-dermal injection of type VII collagen) 
    • Gene therapy
    • Revertant mosaicism
    • Gene correction technologies (ex. CRISPR)

    DEBRA International has developed clinical practice guidelines for different aspects of treating EB including wound care and pain management. Click on the link to see their completed guidelines.

    Management Guidelines

    • DebRA International has developed clinical practice guidelines for epidermolysis bullosa which provide recommendations for clinical care. These clinical guidelines are for patients as well as healthcare professionals.

      Organizations

      Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

      Organizations Supporting this Disease

        Social Networking Websites

        • RareConnect is an online social network for patients and families to connect with one another and share their experience living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders). Click on the link above to view the community for Epidermolysis bullosa.

          Learn more

          These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

          Where to Start

          • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
          • Genetics Home Reference (GHR) contains information on Dominant dystrophic epidermolysis bullosa. This website is maintained by the National Library of Medicine.
          • The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. Click on the link to view information on this topic.
          • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

            In-Depth Information

            • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
            • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
            • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
            • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
            • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
            • PubMed is a searchable database of medical literature and lists journal articles that discuss Dominant dystrophic epidermolysis bullosa. Click on the link to view a sample search on this topic.

              References

              1. Dystrophic EB. DebRA of America. https://www.debra.org/dystrophic. Accessed 4/7/2016.
              2. M Peter Marinkovich. Epidermolysis bullosa. Medscape. January 8, 2014; https://emedicine.medscape.com/article/1062939-overview.
              3. Dystrophic epidermolysis bullosa. Genetics Home Reference. January 2008; https://ghr.nlm.nih.gov/condition/dystrophic-epidermolysis-bullosa.
              4. Pfendner EG & Lucky Aw. Dystrophic Epidermolysis Bullosa. GeneReviews. February 26, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1304/.
              5. Satoru Shinkuma. Dystrophic epidermolysis bullosa: a review. Clin Cosmet Investig Dermatol. 2015; 8:275-284. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451851/.
              6. Dystrophic epidermolysis bullosa. Genetics Home Refernce. January 2008; https://ghr.nlm.nih.gov/condition/dystrophic-epidermolysis-bullosa. Accessed 1/31/2014.
              7. Questions and Answers about Epidermolysis Bullosa. National Institute of Arthritis and Musculoskeletal and Skin Diseases. November 2013; https://www.niams.nih.gov/Health_Info/Epidermolysis_Bullosa/.
              8. Dystrophic Epidermolysis Bullosa. Gene Reviews. February 26, 2015; https://www.ncbi.nlm.nih.gov/books/NBK1304/.
              9. Jouni Uitto, Leena Bruckner-Tuderman, Angela M. Christiano , John A. McGrath, Cristina Has, Andrew P. South, Brett Kopelan, E. Clare Robinson. Progress toward Treatment and Cure of Epidermolysis Bullosa: Summary of DEBRA International Research Symposium EB2015. Journal of Investigative Dermatology. 2016; 136:352-358. https://www.ncbi.nlm.nih.gov/pubmed/26802230.

              Rare Nephrology News