Rare Neurology News

Disease Profile

Spondylodysplastic 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)

Proteodermatan sulfate, defective biosynthesis of; PDS, defective biosynthesis of; Dermatan sulfate proteoglycan;

Categories

Congenital and Genetic Diseases; Metabolic disorders; Musculoskeletal Diseases;

Summary

Spondylodysplastic Ehlers-Danlos syndrome (EDS) is a subtype of the EDS, a group of genetic disorders of the connective tissue, which is the material between body cells that gives tissues form and strength. Ehlers-Danlos syndromes primarily affects the skin, hair, and skeletal system. Symptoms usually begin by childhood or adolescence. Like people with other types of EDS, people with Spondylodysplastic EDS have unusually flexible joints; loose, elastic skin; and easy scarring. Features that are unique to this type include short stature; bowing of the legs; weak muscle tone; sparse scalp hair and eyebrows; soft, doughy skin; and thin, translucent skin (which can cause the face to look older).[1] Additional symptoms may include bone weakness, weak muscle tone, mild intellectual disability, and pes planus.[2][3] Spondylodysplastic EDS may be caused by mutations in the B4GALT7 gene, the B3GALT6, or the SLC39A13 gene.[3] It is inherited in an autosomal recessive pattern.[4] Treatment depends on the symptoms that are present.

Symptoms

Common symptoms of spondylodysplastic Ehlers-Danlos syndrome include:[5][1][6][2][3]

  • Progressive short stature in childhood, which can result in short stature as an adult (less than 152cm)
  • Poor muscle tone (hypotonia), ranging from severe and present from birth, to mild and later-onset
  • Bowing of limbs

Other symptoms include:[3][5]

  • Skin hyperextensibility; soft, doughy skin; thin, translucent skin
  • Pes planus (flat feet)
  • Delayed motor development
  • Fragile bones from low bone mineral density (osteopenia)
  • Mild intellectual disabilities or learning disabilities
  • Eye problems
  • Characteristic facial features (triangular face, wide-spaced eyes, proptosis ("bulging" eyes), narrow mouth, low-set ears, sparse scalp hair, flat face, wide forehead, blue sclerae, abnormal teeth, and cleft palate/bifid uvula)
  • Thin, curly hair; sparse eyebrows and eyelashes
  • Joint contractures and hypermobility
  • Loose, elastic skin on the face

The former name for spondylodysplastic Ehlers-Danlos syndrome was "EDS, progeroid type." Although "progeroid" means "appearance similar to old age," affected people do not actually have premature aging and are not expected to have a shortened life span.

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.

Cause

Spondylodysplastic Ehlers-Danlos syndrome (spEDS) can be caused by changes (mutations) in both of a person's copies of the B4GALT7 gene, which is located on chromosome 5. This gene provides instructions for making an enzyme that is involved in the production of collagen (the main protein in connective tissue). When not enough enzyme is made by the B4GALT7 genes, collagen is not formed correctly in connective tissue. The symptoms of the disorder are caused by weak connective tissue.[6] Researchers are still studying exactly how mutations in the B4GALT7 gene cause the signs and symptoms.[7][3]

Some cases are caused by mutations in the B3GALT6 gene. People with mutations in this gene may have kyphoscoliosis, joint hypermobility, contractures, peculiar face, slender and tapered fingers, abnormal teeth, osteoporosis, aortic aneurisms, and lung problems. The B3GALT6 gene encodes a protein that is part of the connective tissue.[3][8]

Other cases are caused by mutations in the SLC39A13 gene. These cases are characterized by protuberant eyes, wrinkled palms of the hands, tapering fingers, and hypermobility of distal joints. It is not known how mutations in this gene result in the symptoms. The SLC39A13 gene produces a protein that regulates the entrance of zinc into cells.[3][9]

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

    People with spondylodysplastic Ehlers-Danlos syndrome can benefit from a variety of treatments depending on their symptoms. Affected children with weak muscle tone and delayed development might benefit from physiotherapy to improve muscle strength and coordination. People with joint pain might benefit from anti-inflammatory medications. Lifestyle changes or precautions during exercise or intense physical activity may be advised to reduce the risk of accidents involving the skin and bones.[4] It is recommended that affected individuals discuss treatment options with their healthcare provider.

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

            References

            1. Kresse H, Rosthoj S, Quentin E, Hollmann J, Glossl J, Okada S, Tonnesen T. Glycosaminoglycan-free small proteoglycan core protein is secreted by fibroblasts from a patient with a syndrome resembling progeroid. Am. J. Hum. Genet. 1987; 41:436-453.
            2. Hernandez A. et al. Ehlers-Danlos features with progeroid facies and mild mental retardation: further delineation of the syndrome. Clinical Genetics. 1986; 30:456-461.
            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. Wenstrup R, Paepe AD. Ehlers-Danlos Syndrome, Classic Type. GeneReviews. 2011; https://www.ncbi.nlm.nih.gov/books/NBK1244/#eds.Differential_Diagnosis.
            5. Faiyaz-Ul-Haque M. et al. A novel missense mutation in the galactosyltransferase-I (B4GALT7) gene in a family exhibiting facioskeletal anomalies and Ehlers-Danlos syndrome resembling the progeroid type. Am. J. Med. Genet.. 2004; 128(A):39-45.
            6. Quentin E, Gladen A, Roden L, Kresse H. A genetic defect in the biosynthesis of dermatan sulfate proteoglycan: Galactosyltransferase I deficiency in fibroblasts from a patient with a progeroid syndrome. Proc. Natl. Acad. Sci. 1990; 87:1342-1346.
            7. https://ghr.nlm.nih.gov/gene/B4GALT7. Genetics Home Reference. 2017; B4GALT7 gene.
            8. B3GALT6 gene. Genetics Home Reference. 2017; https://ghr.nlm.nih.gov/gene/B3GALT6#conditions.
            9. SLC39A13 gene. Genetics Home Reference. 2017; https://ghr.nlm.nih.gov/gene/SLC39A13.

            Rare Neurology News

            Medical Terms Other Names
            Learn More:
            HPO ID
            80%-99% of people have these symptoms
            Aortic valve stenosis
            Narrowing of aortic valve
            0001650
            Arachnodactyly
            Long slender fingers
            Spider fingers

            [ more ]

            0001166
            Cryptorchidism
            Undescended testes
            Undescended testis

            [ more ]

            0000028
            Cutis laxa
            Loose and inelastic skin
            0000973
            Epicanthus
            Eye folds
            Prominent eye folds

            [ more ]

            0000286
            Flexion contracture
            Flexed joint that cannot be straightened
            0001371
            Gingivitis
            Inflamed gums
            Red and swollen gums

            [ more ]

            0000230
            Global developmental delay
            0001263
            Hyperextensible skin
            Stretchable skin
            Skin hyperelasticity
            Hyperelastic skin

            [ more ]

            0000974
            Lipodystrophy
            Inability to make and keep healthy fat tissue
            0009125
            Long toe
            Increased length of toes
            Long toes

            [ more ]

            0010511
            Macrocephaly
            Increased size of skull
            Large head
            Large head circumference

            [ more ]

            0000256
            Muscular hypotonia
            Low or weak muscle tone
            0001252
            Palmoplantar cutis gyrata
            0007469
            Pes planus
            Flat feet
            Flat foot

            [ more ]

            0001763
            Progeroid facial appearance
            Premature aged appearance
            0005328
            Pulmonic stenosis
            Narrowing of pulmonic valve
            0001642
            Short stature
            Decreased body height
            Small stature

            [ more ]

            0004322
            Testicular torsion
            0100813
            Thin skin
            0000963
            30%-79% of people have these symptoms
            Abnormal facial shape
            Unusual facial appearance
            0001999
            Abnormality of skin pigmentation
            Abnormal pigmentation
            Abnormal skin color
            Abnormal skin pigmentation
            Abnormality of pigmentation
            Pigmentary changes
            Pigmentary skin changes
            Pigmentation anomaly

            [ more ]

            0001000
            Atrophic scars
            Sunken or indented skin due to damage
            0001075
            Narrow mouth
            Small mouth
            0000160
            Osteopenia
            0000938
            Skeletal dysplasia
            0002652
            Skeletal muscle atrophy
            Muscle degeneration
            Muscle wasting

            [ more ]

            0003202
            Sparse and thin eyebrow
            Thin, sparse eyebrows
            0000535
            Sparse eyelashes
            Scant eyelashes
            Scanty eyelashes
            Thin eyelashes

            [ more ]

            0000653
            Sparse scalp hair
            Reduced/lack of hair on scalp
            Scalp hair, thinning
            Sparse, thin scalp hair
            sparse-absent scalp hair

            [ more ]

            0002209
            Telecanthus
            Corners of eye widely separated
            0000506
            Wide nasal bridge
            Broad nasal bridge
            Broad nasal root
            Broadened nasal bridge
            Increased breadth of bridge of nose
            Increased breadth of nasal bridge
            Increased width of bridge of nose
            Increased width of nasal bridge
            Nasal bridge broad
            Wide bridge of nose
            Widened nasal bridge

            [ more ]

            0000431
            5%-29% of people have these symptoms
            Abnormality of primary teeth
            Abnormality of baby teeth
            Abnormality of milk teeth

            [ more ]

            0006481
            Genu recurvatum
            Back knee
            Knee hyperextension

            [ more ]

            0002816
            Joint hyperflexibility
            Joints move beyond expected range of motion
            0005692
            Kyphoscoliosis
            0002751
            Mild global developmental delay
            0011342
            Phalangeal dislocation
            0006243
            Talipes equinovalgus
            0001772
            Talipes equinovarus
            Club feet
            Club foot
            Clubfeet
            Clubfoot

            [ more ]

            0001762
            1%-4% of people have these symptoms
            Accelerated skeletal maturation
            Advanced bone age
            Early bone maturation

            [ more ]

            0005616
            Bifid uvula
            0000193
            Blue sclerae
            Whites of eyes are a bluish-gray color
            0000592
            Broad forehead
            Increased width of the forehead
            Wide forehead

            [ more ]

            0000337
            Craniosynostosis
            0001363
            Dislocated radial head
            0003083
            Flared metaphysis
            Flared wide portion of long bone
            0003015
            Flat face
            Flat facial shape
            0012368
            Generalized hypotonia
            Decreased muscle tone
            Low muscle tone

            [ more ]

            0001290
            Hypermetropia
            Farsightedness
            Long-sightedness

            [ more ]

            0000540
            Hypertelorism
            Wide-set eyes
            Widely spaced eyes

            [ more ]

            0000316
            Low-set ears
            Low set ears
            Lowset ears

            [ more ]

            0000369