Rare Rheumatology News

Disease Profile

Classical-like 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

Neonatal

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

no.svg

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

rnn-autosomalrecessive.svg

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.

no.svg

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

no.svg

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.

no.svg

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.

no.svg

Not applicable

no.svg

Other names (AKA)

EDS due to TNX deficiency; TNX deficiency; Ehlers-Danlos syndrome, classic-like type;

Categories

Congenital and Genetic Diseases; Digestive Diseases; Lung Diseases;

Summary

Classical-like Ehlers-Danlos syndrome (EDS due to tenascin-X (TNX) deficiency) is a form of Ehlers Danlos Syndrome (EDS) characterized by an unusually large range of joint movement (hypermobility), skin that is soft, stretchy, and fragile and easy bruising. Other signs and symptoms might include: muscle weakness and wasting (atrophy), and protrusion of part of the stomach through the diaphragm in the chest cavity (hiatal hernia).[1][2]

Classical-like EDS is caused by mutations in both copies of the TNXB gene and is inherited in an autosomal recessive manner; however, some individuals with a mutation in only one copy of the TNXB gene can have symptoms similar to EDS hypermobility type including joint hypermobility and soft skin. These individuals do not typically have easy bruising and stretchy skin.[2][3]

Some individuals with classical-like EDS can have larger deletions of genetic material including other genes. These individuals may have additional symptoms. For example, sometimes deletions include both the TNXB gene and the CYP21A2 gene. Mutations within this gene are associated with one type of congenital adrenal hyperplasia (CAH), a group of genetic conditions that affect the glands that sit on top of the kidneys (adrenal glands).[3][4]

There is no cure for classical-like EDS. The treatment and management is focused on preventing serious complications and relieving associated signs and symptoms.[3]

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
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
30%-79% of people have these symptoms
Arthralgia
Joint pain
0002829
Bruising susceptibility
Bruise easily
Easy bruisability
Easy bruising

[ more ]

0000978
Fatigue
Tired
Tiredness

[ more ]

0012378
Hyperextensible skin
Hyperelastic skin
Skin hyperelasticity
Stretchable skin

[ more ]

0000974
Muscular hypotonia
Low or weak muscle tone
0001252
Myalgia
Muscle ache
Muscle pain

[ more ]

0003326
Proximal muscle weakness
Weakness in muscles of upper arms and upper legs
0003701
Sensory neuropathy
Damage to nerves that sense feeling
0000763
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting

[ more ]

0003202
Thin skin
0000963
5%-29% of people have these symptoms
Adrenal hypoplasia
Small adrenal glands
0000835
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat

[ more ]

0011675
Gastrointestinal hemorrhage
Gastrointestinal bleeding
0002239
Increased connective tissue
0009025
Mitral valve prolapse
0001634
Muscle fiber splitting
0003555
Precocious atherosclerosis
0004416
Proximal amyotrophy
Wasting of muscles near the body
0007126
Spina bifida occulta
0003298
Stroke
0001297
Percent of people who have these symptoms is not available through HPO
Ambiguous genitalia, female
Atypical appearance of female genitals
0000061
Autosomal recessive inheritance
0000007
Bicornuate uterus
Heart shaped uterus
Heart-shaped uterus

[ more ]

0000813
Hiatus hernia
Stomach hernia
0002036
Joint hypermobility
Double-Jointed
Flexible joints
Increased mobility of joints

[ more ]

0001382
Joint subluxation
0032153
Quadricuspid aortic valve
0031655
Soft skin
0000977
Unilateral renal agenesis
Absent kidney on one side
Missing one kidney
Single kidney

[ more ]

0000122
Vesicoureteral reflux
0000076

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.

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

            References

            1. Victor A. McKusick. EHLERS-DANLOS SYNDROME DUE TO TENASCIN-X DEFICIENCY. In: Cassandra L. Kniffin. OMIM. 8/26/2014; https://omim.org/entry/606408. Accessed 11/8/2016.
            2. TNXB gene. Genetics Home Reference. November 2015; https://ghr.nlm.nih.gov/gene/TNXB. Accessed 11/8/2016.
            3. Levy, Howard P.. Ehlers-Danlos Syndrome, Hypermobility Type. GeneReveiws. March 31, 2016; https://www.ncbi.nlm.nih.gov/books/NBK1279/. Accessed 11/8/2016.
            4. Deborah P. Merke,corresponding author Wuyan Chen, Rachel Morissette, Zhi Xu, Carol Van Ryzin, Vandana Sachdev, Hwaida Hannoush, Sujata M. Shanbhag, Ana T. Acevedo, Miki Nishitani, Andrew E. Arai, Nazli B. McDonnell. Tenascin-X Haploinsufficiency Associated with Ehlers-Danlos Syndrome in Patients with Congenital Adrenal Hyperplasia. J Clin Endocrinol Metab. Jan. 2, 2013; 98(2):E379-E387. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3565116/.