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Disease Profile

Dermatosparaxis Ehlers-Danlos syndrome

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.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

Q79.6

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)

Dermatosparaxis; Ehlers-Danlos syndrome type 7C (formerly); Ehlers-Danlos syndrome, dermatosparaxis type;

Categories

Congenital and Genetic Diseases; Connective tissue diseases; Skin Diseases

Summary

Dermatosparaxis Ehlers-Danlos syndrome (dEDS) is an inherited connective tissue disorder that is caused by defects in a protein called collagen. Common symptoms include soft, doughy skin that is extremely fragile; saggy, redundant skin, especially on the face; hernias; and mild to severe joint hypermobility.[1][2][3] EDS, dermatosparaxis type is caused by changes (mutations) in the ADAMTS2 gene and is inherited in an autosomal recessive manner.[4] Treatment and management is focused on preventing serious complications and relieving associated signs and symptoms.[5]

Symptoms

The signs and symptoms of dermatosparaxis EDS (dEDS) vary but may include:[1][2][3]

  • Soft, doughy skin that is extremely fragile
  • Severe bruising and scarring
  • Saggy, redundant skin, especially on the face
  • Hernias
  • Short stature
  • Delayed closure of the fontanelles
  • Short fingers
  • Characteristic facial appearance with puffy eyelids, blue sclerae (whites of the eyes), epicanthal folds, downslanting palpebral fissures (outside corners of the eyes that point downward) and micrognathia
  • Rupture of the bladder or diaphragm
  • Mild to severe joint hypermobility

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
Abnormality of subcutaneous fat tissue
Abnormality of fatty tissue below the skin
0001001
Aphasia
Difficulty finding words
Losing words
Loss of words

[ more ]

0002381
Avascular necrosis of the capital femoral epiphysis
0005743
Coxa valga
0002673
Coxa vara
0002812
Dysphasia
0002357
Echolalia
Echoing another person's speech
0010529
Esophagitis
Inflammation of the esophagus
0100633
Excessive wrinkled skin
0007392
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn

[ more ]

0002020
Hiatus hernia
Stomach hernia
0002036
Hip dislocation
Dislocated hips
Dislocation of hip

[ more ]

0002827
Hip dysplasia
0001385
Hyperextensible skin
Hyperelastic skin
Skin hyperelasticity
Stretchable skin

[ more ]

0000974
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Joint stiffness
Stiff joint
Stiff joints

[ more ]

0001387
Muscular hypotonia
Low or weak muscle tone
0001252
Mutism
Inability to speak
Muteness

[ more ]

0002300
Osteomalacia
Softening of the bones
0002749
Osteopenia
0000938
Osteoporosis
0000939
Prolonged bleeding time
0003010
Rickets
Weak and soft bones
0002748
Scarring
0100699
Severe short stature
Dwarfism
Proportionate dwarfism
Short stature, severe

[ more ]

0003510
Thin skin
0000963
30%-79% of people have these symptoms
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
Femoral hernia
0100541
Inguinal hernia
0000023
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Retrognathia
Receding chin
Receding lower jaw
Weak chin
Weak jaw

[ more ]

0000278
Scoliosis
0002650
Percent of people who have these symptoms is not available through HPO
Abnormality of primary molar morphology
Abnormality of shape of baby molar
0006344
Autosomal recessive inheritance
0000007
Blepharochalasis
0010749
Blue sclerae
Whites of eyes are a bluish-gray color
0000592
Bruising susceptibility
Bruise easily
Easy bruisability
Easy bruising

[ more ]

0000978
Delayed closure of the anterior fontanelle
Later than typical closing of soft spot of skull
0001476
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Everted lower lip vermilion
Drooping lower lip
Outward turned lower lip

[ more ]

0000232
Fragile skin
Skin fragility
0001030
Frontal open bite
0200094
Gingival bleeding
Bleeding gums
0000225
Gingival hyperkeratosis
0000222
Gingival overgrowth
Gum enlargement
0000212
Hirsutism
Excessive hairiness
0001007
Hypodontia
Failure of development of between one and six teeth
0000668
Joint laxity
Joint instability
Lax joints
Loose-jointedness
Loosejointedness

[ more ]

0001388
Limb undergrowth
limb shortening
Short limb
Short limbs

[ more ]

0009826
Micromelia
Smaller or shorter than typical limbs
0002983
Motor delay
0001270
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness

[ more ]

0000545
Premature birth
Premature delivery of affected infants
Preterm delivery

[ more ]

0001622
Premature rupture of membranes
0001788
Recurrent mandibular subluxations
0005332
Redundant skin
Loose redundant skin
Redundant skin folds
Sagging, redundant skin

[ more ]

0001582

Cause

Dermatosparaxis EDS (dEDS) is caused by changes (mutations) in the ADAMTS2 gene.[4] This gene encodes an enzyme that helps process several types of "procollagen molecules" (precursors of collagen). Collagen is a protein that provides structure and strength to connective tissues throughout the body. Mutations in ADAMTS2 lead to reduced levels of functional enzyme which interferes with the proper processing of procollagens. As a result, networks of collagen are not assembled properly. This weakens connective tissues and causes the many signs and symptoms associated with dEDS.[6]

Diagnosis

A diagnosis of dermatosparaxis Ehlers-Danlos syndrome (dEDS) is typically based on the presence of characteristic signs and symptoms. The main clinical features for diagnosis (major and minor criteria) include:[7]

  • Major criteria:
  1. Extreme skin fragility with congenital or postnatal skin tears
  2. Characteristic craniofacial features, which are evident at birth or early infancy, or evolve later in childhood
  3. Redundant, almost lax skin, with excessive skin folds at the wrists and ankles
  4. Increased palmar wrinkling
  5. Severe bruisability with a risk of subcutaneous hematomas and haemorrhage
  6. Umbilical hernia
  7. Postnatal growth retardation
  8. Short limbs, hand and feet
  9. Perinatal complications due to connective tissue fragility
  • Minor criteria
    1. Soft and doughy skin texture
    2. Skin hyperextensibility
    3. Atrophic scars
    4. GJH
    5. Complications of visceral fragility (e.g., bladder rupture, diaphragmatic rupture, rectal prolapse)
    6. Delayed motor development
    7. Osteopenia
    8. Hirsutism
    9. Tooth abnormalities
    10. Refractive errors (myopia, astigmatism)
    11. Strabismus
  • Minimal criteria suggestive for dEDS:
      • –Major criterion (1): extreme skin fragility
      • –AND major criterion (2): characteristic craniofacial features

    Plus

      • –Either: one other major criterion
      • –And/or: three minor criteria

    Diagnosis is confirmed by genetic testing showing a change (mutation) in the ADAMTS2 gene.[3][1] When testing is not available a skin biopsy can be ordered to help with the diagnosis but it is not enough to confirm it.[7]

    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

      The treatment of dermatosparaxis EDS (dEDS) is focused on preventing serious complications and relieving associated signs and symptoms. For example, physical therapy may be recommended in children with moderate to severe joint hypermobility. Assistive devices such as braces, wheelchairs, or scooters may also be necessary depending on the severity of joint instability. Hernias may be treated with surgery. Because dEDS is associated with extremely fragile skin, affected people, especially children, may need to use protective bandages or pads over exposed areas, such as the knees, shins, and forehead. Heavy exercise and contact sports may also need to be avoided due to skin fragility and easy bruising.[5]

      Please speak to your healthcare provider if you have any questions about your personal medical management plan.

      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 has an online community for patients and families with this condition so they can connect with others and share their experiences living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders).

          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 Dermatosparaxis Ehlers-Danlos syndrome. This website is maintained by the National Library of Medicine.
          • 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.
              Ehlers-Danlos Syndrome
              Genetics of Ehlers-Danlos syndrome
            • MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
            • 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 Dermatosparaxis Ehlers-Danlos syndrome. Click on the link to view a sample search on this topic.

              References

              1. Pauker SP & Stoler J. Clinical manifestations and diagnosis of Ehlers-Danlos syndromes. UpToDate. February 22, 2016; https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-ehlers-danlos-syndromes.
              2. Solomons J1, Coucke P, Symoens S, Cohen MC, Pope FM, Wagner BE, Sobey G, Black R, Cilliers D. Dermatosparaxis (Ehlers-Danlos type VIIC): prenatal diagnosis following a previous pregnancy with unexpected skull fractures at delivery. Am J Med Genet A. May 2013; 161A(5):1122-1125.
              3. Malfait F1, De Coster P, Hausser I, van Essen AJ, Franck P, Colige A, Nusgens B, Martens L, De Paepe A. The natural history, including orofacial features of three patients with Ehlers-Danlos syndrome, dermatosparaxis type (EDS type VIIC). Am J Med Genet A. November 2004; 131(1):18-28.
              4. Defendi GL. Genetics of Ehlers-Danlos Syndrome. Medscape Reference. August, 2015; https://emedicine.medscape.com/article/943567-overview.
              5. Pauker SP & Stoler J. Overview of the management of Ehlers-Danlos syndromes. UpToDate. 2016; https://www.uptodate.com/contents/overview-of-the-management-of-ehlers-danlos-syndromes.
              6. ADAMTS2. Genetics Home Reference. May 2006; https://ghr.nlm.nih.gov/gene/ADAMTS2.
              7. Malfait F, Francomano C, Byers P et al. The 2017 international classification of the Ehlers–Danlos syndromes. Am J Med Genet C Semin Med Genet. March, 2017; 175(1):8-26. https://onlinelibrary.wiley.com/doi/10.1002/ajmg.c.31552/full.

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