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Disease Profile

Recessive dystrophic epidermolysis bullosa-generalized other

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

Age of onset

Neonatal

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

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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

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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.

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

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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.

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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.

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Not applicable

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Other names (AKA)

Autosomal recessive dystrophic epidermolysis bullosa generalisata mitis; Autosomal recessive dystrophic epidermolysis bullosa, generalized other; Generalized mitis RDEB;

Categories

Congenital and Genetic Diseases; Eye diseases; Skin Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 89842

Definition
Recessive dystrophic epidermolysis bullosa (RDEB)-generalized other, also known as RDEB non-Hallopeau-Siemens type, is a subtype of DEB (see this term) characterized by generalized cutaneous and mucosal blistering that is not associated with severe deformities.

Epidemiology
Its exact prevalence is unknown but this sub-type represents the second most common RDEB, the first one being severe generalized RDEB (RDEBsev gen; see this term). The prevalence of all RDEB sub-types, with the exclusion of RDEB-sev gen, has been estimated at 1/2,040,816 in the United States.

Clinical description
Under the term RDEB-other are grouped a spectrum of phenotypes, showing highly variable severity of the cutaneous and mucosal involvement. The disease manifests at birth or during the neonatal period with generalized blistering. Aplasia cutis congenita (congenital absence of the skin) can also be observed at birth. Healing of blisters results in the development of milia, atrophic scarring (less severe than in RDEBsev gen), dystrophic nails, and, occasionally, albopapuloid lesions (ivory-white colored scar-like papules) and scalp abnormalities. In some patients, the scarring phenomena can lead to a certain degree of pseudosyndactyly and loss of nail plates. Extracutaneous involvement is similar but less severe than in severe generalized RDEB with no hand/foot deformities associated with this disease. Oral cavity lesions and excessive dental caries are common. Patients have a lower risk of esophageal strictures and corneal injury than RDEB-sev gen. Growth delay and anemia are uncommon. Genitourinary tract involvement is rare. Patients have an increased risk of developing squamous cell carcinomas (35.8% by age 50 according to the U.S. EB national registry).

Etiology
The disease is caused by mutations within the type VII collagen gene (COL7A1) that lead to an alteration of function or a reduction in the amounts of collagen VII. This impairs collagen VII assembly into anchoring fibrils which anchor the basement membrane to the underlying dermis. This in turn causes reduced skin resistance to minor trauma.

Diagnostic methods
Diagnosis is suspected at clinical examination and is confirmed by immunofluorescence antigen mapping and/or transmission electron microscopy on skin samples showing a cleavage plane located below the lamina densa of the cutaneous basement membrane zone. Genetic testing confirms the diagnosis.

Differential diagnosis
The differential diagnosis includes other forms of EB. In the neonatal period, aplasia cutis congenita, herpes simplex infection, congenital erosive and vesicular dermatosis, epidermolytic ichthyosis, linear IgA bullous dermatosis, bullous pemphigoid, neonatal pemphigus and pemphigoid gestationis, bullous impetigo, and staphylococcal scalded skin syndrome (see these terms) may need to be considered.

Antenatal diagnosis
DNA-based prenatal diagnosis is possible for at risk pregnancies.

Genetic counseling
Transmission is autosomal recessive.

Management and treatment
Management is preventive: protective padding of the skin reduces blistering and careful wound care prevents secondary infection and reduces scarring. Oral hygiene is important for management of caries. Nutritional requirements should be evaluated by a dietitian. Esophageal strictures are treated by balloon dilatation with fluoroscopic guidance. A regular follow-up is necessary for the surveillance of SCC. The treatment of SCC is surgical and involves full-thickness excision with wide margins.

Prognosis
In most cases, life expectancy is normal. However, there is an increased risk of development of metastasizing squamous cell carcinomas with a cumulative risk of mortality of 21.5% by age 55 according to the U.S. EB national registry.

Visit the Orphanet disease page for more resources.

Symptoms

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
80%-99% of people have these symptoms
Abnormal blistering of the skin
Blistering, generalized
Blisters

[ more ]

0008066
Abnormal circulating selenium concentration
0031903
Anemia
Low number of red blood cells or hemoglobin
0001903
Atypical scarring of skin
Atypical scarring
0000987
Fragile skin
Skin fragility
0001030
30%-79% of people have these symptoms
Carious teeth
Dental cavities
Tooth cavities
Tooth decay

[ more ]

0000670
Chronic cutaneous wound
0032676
Constipation
0002019
Decreased plasma carnitine
0003234
Decreased serum iron
0040303
Decreased serum zinc
0031831
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
Esophageal stricture
Narrowing of esophagus due to inflammation and scar tissue
0002043
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn

[ more ]

0002020
Hypoalbuminemia
Low blood albumin
0003073
Irregular hyperpigmentation
0007400
Low levels of vitamin D
Deficient in vitamin D
Vitamin D deficiency

[ more ]

0100512
Malnutrition
0004395
Milia
Milk spot
0001056
Recurrent skin infections
Skin infections, recurrent
0001581
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting

[ more ]

0003202
Skin erosion
0200041
5%-29% of people have these symptoms
Absent toenail
0001802
Anal fissure
0012390
Ankyloglossia
Tongue tied
0010296
Anxiety
Excessive, persistent worry and fear
0000739
Aplasia cutis congenita
Absence of part of skin at birth
0001057
Corneal erosion
Damage to outer layer of the cornea of the eye
0200020
Delayed puberty
Delayed pubertal development
Delayed pubertal growth
Pubertal delay

[ more ]

0000823
Depressivity
Depression
0000716
Dilated cardiomyopathy
Stretched and thinned heart muscle
0001644
Flexion contracture
Flexed joint that cannot be straightened
0001371
Gastrostomy tube feeding in infancy
0011471
Mitten deformity
0004057
Nail dysplasia
Atypical nail growth
0002164
Narrow mouth
Small mouth
0000160
Nevus
Mole
0003764
Visual loss
Loss of vision
Vision loss

[ more ]

0000572
1%-4% of people have these symptoms
Squamous cell carcinoma
0002860

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

    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.

    In-Depth Information

    • 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.
    • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.