Dominant dystrophic epidermolysis bullosa

Title

Other Names:

Dominant dystrophic epidermolysis bullosa, generalized; DDEB, generalized; DDEB-gen; Dominant dystrophic epidermolysis bullosa, generalized; DDEB, generalized; DDEB-gen; Epidermolysis bullosa dystrophica, autosomal dominant; Dystrophic epidermolysis bullosa, autosomal dominant; Epidermolysis bullosa dystrophica, Cockayne-Touraine type (formerly); Epidermolysis bullosa dystrophica, Pasini type (formerly); Autosomal dominant dystrophic epidermolysis bullosa, Pasini and Cockayne-Touraine types; DDEB, Pasini and Cockayne-Touraine types; Generalized dominant dystrophic epidermolysis bullosa See More

Categories:

Congenital and Genetic Diseases; Skin Diseases

Summary 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]

Last updated: 4/7/2016

Symptoms 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]

Last updated: 4/8/2016

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Abnormality of the fingernails	Very frequent (present in 80%-99% of cases)
Abnormality of the toenails	Very frequent (present in 80%-99% of cases)
Cheilitis	Very frequent (present in 80%-99% of cases)
Skin vesicle	Very frequent (present in 80%-99% of cases)
Atrophic scars	Frequent (present in 30%-79% of cases)
Carious teeth	Frequent (present in 30%-79% of cases)
Hypopigmented skin patches	Frequent (present in 30%-79% of cases)
Anemia	Occasional (present in 5%-29% of cases)
Corneal erosion	Occasional (present in 5%-29% of cases)
Dysphagia	Occasional (present in 5%-29% of cases)
Esophageal stricture	Occasional (present in 5%-29% of cases)
Milia	Occasional (present in 5%-29% of cases)
Urethral stricture	Occasional (present in 5%-29% of cases)
Urinary retention	Occasional (present in 5%-29% of cases)
Abnormal blistering of the skin	-
Autosomal dominant inheritance	-
Congenital onset	-
Nail dysplasia	-
Nail dystrophy	-

Last updated: 9/1/2017

Cause 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.

Last updated: 4/6/2016

Inheritance Inheritance

Dominant dystrophic epidermolysis bullosa (DDEB) has an autosomal dominant pattern of inheritance. Autosomal dominant inheritance means that one copy of the gene with the mutation in each cell is sufficient to cause the disorder. About 70 percent of individuals with DDEB have inherited a COL7A1 mutation from an affected parent. The remaining 30 percent have the condition as a result of a new (de novo) mutation in the COL7A1 gene. These cases occur in people with no history of the disorder in their family. Regardless of whether an individual with an autosomal dominant condition has inherited the mutation or has a new mutation, each child of the affected individual has a 50% (1 in 2) chance of also having the condition, and a 50% chance of not having the condition.^[8]

Last updated: 4/7/2016

Diagnosis 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 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.

Last updated: 4/8/2016

Management Guidelines

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.

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Patient Registry

The EBCare Registry is a resource for individuals and families affected by all forms of epidermolysis bullosa (EB) and qualified researchers working on approved EB research projects. The Registry itself is a research project and the data collected through the Registry will help characterize the condition of people living with all types of EB.

Organizations 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

DebRA International
Am Heumarkt 27/3
1030 Vienna
Austria
Telephone: +43 1 876 40 30-0
Fax: +43 1 876 40 30-30
E-mail: office@debra-international.org
Website: http://www.debra-international.org/
Dystrophic Epidermolysis Bullosa Research Association of America (DEBRA of America)
75 Broad Street
Suite 300
New York, NY 10004
Toll-free: 855-CURE-4-EB
Telephone: 212-868-1573
Fax: 212-868-9296
E-mail: staff@debra.org
Website: http://www.debra.org
Epidermolysis Bullosa (EB) Center
The Epidermolysis Bullosa Center
Cincinnati Children's Hospital Medical Center
MLD 3004
3333 Burnet Avenue
Cincinnati, OH 45229-3039
Telephone: 513-636-2009
E-mail: ebcenter@cchmc.org
Website: http://www.cincinnatichildrens.org/svc/alpha/e/epidermolysis-bullosa/
Epidermolysis Bullosa Medical Research Foundation (EBMRF)
2757 Anchor Ave
Los Angeles, CA 90064
Telephone: 310-205-5119
E-mail: a.pett@bep-la.com
Website: http://www.ebkids.org

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.

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Healthcare Resources

The Dystrophic Epidermolysis Bullosa Research Association of America, Inc. (DEBRA) offers a National Physician Referral Service that connects people suffering with epidermolysis bullosa to qualified and knowledgeable health care professionals in their communities. Click on the link above to learn more about this and other services offered by the DEBRA.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More 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

Genetics Home Reference (GHR) contains information on Dominant dystrophic epidermolysis bullosa. This website is maintained by the National Library of Medicine.
MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
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

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.

News & Events News & Events

News

Don’t Miss the NCATS Toolkit for Patient-Focused Therapy Development Event
August 31, 2017
Funding Opportunities Now Available for the Undiagnosed Diseases Network (UDN) Phase II
August 30, 2017
IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017

NCATS Co-Sponsored Conferences

2013 Epithelial Differentiation and Keratinization GRC/GRS Saturday, May 11, 2013 - Sunday, May 12, 2013
Location: Renaissance Tuscany Il Ciocco Resort, Lucca (Barga), Italy
Description: Novel findings in rare disease gene identification, together with studies on disease mechanisms in human patients and in mouse models, will suggest novel therapeutic approaches and form the basis for new prenatal tests. Investigators including Drs. Tolar and Oro will report on the results of bone marrow stem cell therapies and small molecule therapeutics in human patients with rare skin diseases; successful outcomes of these clinical trials will spur expansion of the use of these approaches in patients. Gene correction in patient derived iPS is an exciting potential therapeutic approach to both recessive and dominant genetic skin diseases. Drs. Roop and Christiano will provide updates on derivation and characterization of iPS from patients, and will discuss approaches to gene correction and differentiation of iPS into skin cell lineages for potential use in grafting procedures

Contact: Carl C. Baker, M.D., Ph.D., NIAMS(301) 594-5017ccb@nih.gov

Co-funding Institute(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases, Office of Rare Diseases Research

Related Diseases Related Diseases

The following diseases are related to Dominant dystrophic epidermolysis bullosa. If you have a question about any of these diseases, you can contact GARD.

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My cousin has dominant dystrophic epidermolysis bullosa. Is there a chance her future children might also have the condition? Is this condition curable? See answer

Have a question? Contact a GARD Information Specialist.

References References

Dystrophic EB. DebRA of America. http://www.debra.org/dystrophic. Accessed 4/7/2016.
M Peter Marinkovich. Epidermolysis bullosa. Medscape. January 8, 2014; http://emedicine.medscape.com/article/1062939-overview.
Dystrophic epidermolysis bullosa. Genetics Home Reference. January 2008; http://ghr.nlm.nih.gov/condition/dystrophic-epidermolysis-bullosa.
Pfendner EG & Lucky Aw. Dystrophic Epidermolysis Bullosa. GeneReviews. February 26, 2015; http://www.ncbi.nlm.nih.gov/books/NBK1304/.
Satoru Shinkuma. Dystrophic epidermolysis bullosa: a review. Clin Cosmet Investig Dermatol. 2015; 8:275-284. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4451851/.
Dystrophic epidermolysis bullosa. Genetics Home Refernce. January 2008; http://ghr.nlm.nih.gov/condition/dystrophic-epidermolysis-bullosa. Accessed 1/31/2014.
Questions and Answers about Epidermolysis Bullosa. National Institute of Arthritis and Musculoskeletal and Skin Diseases. November 2013; http://www.niams.nih.gov/Health_Info/Epidermolysis_Bullosa/.
Dystrophic Epidermolysis Bullosa. Gene Reviews. February 26, 2015; http://www.ncbi.nlm.nih.gov/books/NBK1304/.
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. http://www.ncbi.nlm.nih.gov/pubmed/26802230.