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Disease Profile

Kyphoscoliotic 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.

Unknown

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)

EDS VIA; EDS, kyphoscoliotic type; EDS, oculoscoliotic type;

Categories

Congenital and Genetic Diseases; Eye diseases; Skin Diseases

Summary

Kyphoscoliotic Ehlers-Danlos syndrome is an inherited connective tissue disorder that is caused by defects in a protein called collagen. Common signs and symptoms include hyperextensible skin that is fragile and bruises easily; joint hypermobility; severe hypotonia at birth; progressive kyphoscoliosis (kyphosis and scoliosis); and fragility of the sclera.[1][2] kyphoscoliosis EDS is caused by changes (mutations) in the PLOD1 gene or the FKBP14 gene  and it is inherited in an autosomal recessive manner.[1][3] Treatment is focused on preventing serious complications and relieving associated signs and symptoms.[1][4]

Symptoms

The signs and symptoms of kyphoscoliotic EDS vary but may include:

  • Hyperextensible skin that is fragile and bruises easily
  • Joint hypermobility that leads to frequent dislocations and subluxations (partial dislocations)
  • Severe hypotonia at birth
  • Progressive kyphoscoliosis (kyphosis and scoliosis), present at birth or within the first year of life
  • Scleral fragility
  • Abnormal wound healing
  • "Marfanoid habitus" which is characterized by long, slender fingers (arachnodactyly); unusually long limbs; and a sunken chest (pectus excavatum) or protruding chest (pectus carinatum)
  • Fragile arteries that are prone to rupture
  • Delayed motor development
  • Unusually small corneas
  • Osteopenia (low bone density)
  • Congenital clubfoot
  • Cardiovascular abnormalities such as mitral valve prolapse or aortic root dilatation (enlargement of the blood vessel that distributes blood from the heart to the rest of the body)

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 enzyme/coenzyme activity
0012379
Bruising susceptibility
Bruise easily
Easy bruisability
Easy bruising

[ more ]

0000978
Fragile skin
Skin fragility
0001030
Hyperextensible skin
Hyperelastic skin
Skin hyperelasticity
Stretchable skin

[ more ]

0000974
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Neonatal hypotonia
Low muscle tone, in neonatal onset
0001319
Osteopenia
0000938
Osteoporosis
0000939
Thoracic kyphoscoliosis
0005659
30%-79% of people have these symptoms
Disproportionate tall stature
0001519
Generalized joint laxity
Hypermobility of all joints
0002761
Microcornea
Cornea of eye less than 10mm in diameter
0000482
Talipes equinovarus
Club feet
Club foot
Clubfeet
Clubfoot

[ more ]

0001762
5%-29% of people have these symptoms
Aortic aneurysm
Bulge in wall of large artery that carries blood away from heart
0004942
Aortic dissection
Tear in inner wall of large artery that carries blood away from heart
0002647
Arterial dissection
0005294
Arterial rupture
0025019
Blue sclerae
Whites of eyes are a bluish-gray color
0000592
Congenital bilateral hip dislocation
0008780
Decreased muscle mass
0003199
Delayed gross motor development
Delayed motor skills
0002194
Distal joint laxity
0020152
EMG: myopathic abnormalities
0003458
Generalized muscle weakness
0003324
Glaucoma
0000501
Hip subluxation
Partial hip dislocation
0030043
Hypermetropia
Farsightedness
Long-sightedness

[ more ]

0000540
Impaired vibratory sensation
Decreased vibration sense
Decreased vibratory sense
Diminished vibratory sense
Impaired vibratory sense

[ more ]

0002495
Inguinal hernia
0000023
Mitral valve prolapse
0001634
Muscle fiber atrophy
Muscle fiber degeneration
0100295
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness

[ more ]

0000545
Patellar dislocation
Dislocated kneecap
0002999
Pectus excavatum
Funnel chest
0000767
Poor wound healing
0001058
Reduced tendon reflexes
0001315
Retinal detachment
Detached retina
0000541
Scleral rupture
0025513
Shoulder subluxation
Partial shoulder dislocation
0003835
Umbilical hernia
0001537
Widened atrophic scar
0031158
1%-4% of people have these symptoms
Abnormal venous morphology
Abnormal vein
0002624
Abnormality of the brachial nerve plexus
0045052
Abnormality of the pinna
Abnormally shaped ears
Auricular malformation
Deformed ears
Malformed ears

[ more ]

0000377
Congestive heart failure
Cardiac failure
Cardiac failures
Heart failure

[ more ]

0001635
Elbow flexion contracture
Contractures of elbows
Elbow contracture
Elbow contractures

[ more ]

0002987
High, narrow palate
Narrow, high-arched roof of mouth
Narrow, highly arched roof of mouth

[ more ]

0002705
Impaired tandem gait
Clumsy tandem walking
0031629
Peripheral axonal neuropathy
0003477
Pes planus
Flat feet
Flat foot

[ more ]

0001763
Recurrent pneumonia
0006532
Restrictive ventilatory defect
Stiff lung or chest wall causing decreased lung volume
0002091
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Trigonocephaly
Triangular skull shape
Wedge shaped skull

[ more ]

0000243
Wrist drop
0031189
Percent of people who have these symptoms is not available through HPO
Abnormality of metabolism/homeostasis
Laboratory abnormality
Metabolism abnormality

[ more ]

0001939
Arachnodactyly
Long slender fingers
Spider fingers

[ more ]

Cause

Kyphoscoliotic Ehlers-Danlos syndrome (EDS) is caused by changes (mutations) in the PLOD1 gene, and, rarely, in the FKBP14 gene.[1][3] This gene gives the body instructions to make (encodes) an enzyme that helps process molecules that allow collagen to form stable interactions with one another. Collagen is a protein that provides structure and strength to connective tissues throughout the body. Mutations in the PLOD1 gene lead to reduced levels of functional enzyme which disrupt networks of collagen throughout the body. This weakens the connective tissues and leads to the characteristic signs and symptoms associated with EDS, kyphoscoliosis type.[5] The FKBP14 gene encodes a protein which is a member of the FK506-binding protein family of peptidyl-prolyl cis-trans isomerases. The encoded protein is found in the lumen of the endoplasmic reticulum, where it is thought to accelerate protein folding. It is not known how the mutations in this gene lead to the EDS.[6]

Diagnosis

A diagnosis of kyphoscoliotic Ehlers-Danlos syndrome (kEDS) is typically based on the presence of characteristic signs and symptoms. The following tests may then be recommended to confirm the diagnosis:[1][2]

  • Urine tests and/or a skin biopsy to detect deficiencies in certain enzymes that are important for collagen formation
  • Genetic testing for changes (mutations) in the PLOD1 gene or in the FKBP14 gene.

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 kyphoscoliotic Ehlers-Danlos syndrome is focused on preventing serious complications and relieving signs and symptoms. For example, physical therapy may be recommended in children with hypotonia and delayed motor development. This treatment can also help improve joint stability. Assistive devices such as braces may be necessary depending on the severity of joint instability. Depending on the severity of the kyphoscoliosis (kyphosis and scoliosis), surgery may be necessary. Because kyphoscoliotic EDS is associated with fragile skin with abnormal wound healing, affected people, especially children, may need to wear protective bandages or pads over exposed areas, such as the knees, shins, and forehead. Regular follow-up may be recommended to check for development or progression of abnormalities of the eyes, heart, and other parts of the body.[1][4]

    GeneReview's Web site offers more specific information regarding the treatment and management of kyphoscoliotic EDS. Please click on the link to access this resource.

    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 Kyphoscoliotic 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

          • 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.
            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 Kyphoscoliotic Ehlers-Danlos syndrome. Click on the link to view a sample search on this topic.

            References

            1. Yeowell HN, Steinmann B. Ehlers-Danlos Syndrome, Kyphoscoliotic Form. GeneReviews. January 2013; https://www.ncbi.nlm.nih.gov/books/NBK1462/.
            2. 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.
            3. 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.
            4. 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.
            5. PLOD1. Genetics Home Reference (GHR). May 2006; https://ghr.nlm.nih.gov/gene/PLOD1.
            6. FKBP14 gene. Genetics Home Reference. 2017; https://ghr.nlm.nih.gov/gene/FKBP14.

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