Ehlers-Danlos syndrome (EDS) is a genetic disorder that causes problems with the body’s connective tissues, resulting in symptoms such as abnormally mobile joints and stretchy skin. Given that there are more than a dozen types of EDS, each with specific underlying causes and characteristic symptoms, it can be difficult to get a correct diagnosis.
Diagnosing EDS generally starts with a physical examination to look for disease symptoms. Laboratory and genetic tests may be useful for confirming the diagnosis and determining the type of EDS. Because EDS runs in families, a thorough evaluation of a patient’s family history often is important for making the diagnosis.
During a physical examination for EDS, a clinician will look for visible abnormalities associated with connective tissue problems, such as abnormal scarring, and test for symptoms of the disease, like stretchy skin or unusually mobile joints. The specific constellation of symptoms experienced by the individual can be helpful for informing the diagnosis of a specific EDS type.
Joint hypermobility, one of the most common symptoms of EDS, is typically assessed using a scale called the Beighton scoring system. In this system, nine joints are tested to see if they have an abnormal range of movement: the pinky fingers, thumbs, elbows, and knees on both sides of the body, as well as the spine. Each joint that is hypermobile earns a score of one, so scores can range from zero to nine.
In children, a Beighton score of six or higher indicates the most common form of the disease, hypermobile EDS (hEDS). In adolescents and adults up to age 50, a score of five or higher indicates hEDS; for adults over 50, a score of four or higher suggests hEDS.
Mutations in at least 20 different genes are known to cause EDS. Genetic testing involves analyzing a patient’s DNA to look for these disease-causing mutations, which can confirm a diagnosis of EDS, and may be critical for distinguishing the type of disease. Notably, since not all EDS-causing mutations have been identified, it is possible that genetic testing will not identify any mutations even in someone who does have EDS.
Genetic testing is usually done using cells collected from a cheek swab or blood sample. A specialist called a genetic counselor can help to interpret the results of genetic tests, and provide guidance for the patient and any family members. Since EDS runs in families, and it’s possible for someone to carry a disease-causing mutation and not know it, it’s often recommended that close biological relatives of someone with a positive genetic test for EDS also undergo genetic testing.
A skin biopsy is a way to test for connective tissue defects that are characteristic of EDS. Clinicians will collect a sample of a patient’s skin, which is then analyzed under a microscope to look for signs of problems in the connective tissues. Cells collected from biopsies also can be cultured in the lab to look for abnormalities.
Three techniques are commonly used to collect a skin biopsy. In a punch biopsy, a circular blade is used to remove a small, cylindrical section containing all layers of the skin. In a shave biopsy, a razor can be used to scrape along the skin to collect its uppermost layers. An excision biopsy involves the use of a scalpel to cut out a skin lesion for analysis.
Usually a local anesthetic is given to numb the skin before the biopsy is taken. Skin biopsy is generally considered a safe procedure; as with any small wound, the biopsy site should be kept clean to prevent infections.
Techniques like X-ray, MRI, and CT scans can be used to visualize the body’s internal structures to look for abnormalities indicative of EDS. Depending on the type of disease, these may include abnormal curvature of the spine (kyphoscoliosis) and other unusual bone structures, bleeding in joints, hard deposits in the body’s soft tissue, and fragile blood vessels and aneurysm (enlarged blood vessels due to weakness in blood vessel walls).
Certain types of EDS are characterized by abnormal levels of specific compounds in the urine. Measuring the levels of these compounds may be useful in making a diagnosis.
Kyphoscoliotic EDS (kEDS) is characterized by abnormal levels of two compounds called deoxypyridinoline (LP) and pyridinoline (HP). Normally, the ratio of LP to HP levels is about 0.2, but in kEDS, this ratio is usually between 2 and 9.
The LP-to-HP ratio also is elevated in spondylodysplastic EDS, where this ratio is usually about 1.
Last updated: Jan. 4, 2022, by Marisa Wexler MS
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