Classical-like Ehlers-Danlos Syndrome (clEDS) is a rare genetic disorder affecting the body’s connective tissues. This condition is considered ultra-rare, impacting fewer than 1 in 1 million people worldwide. clEDS causes a range of symptoms primarily related to the skin and joints.
Connective tissues provide structure and support to various organs, skin, bones, and blood vessels throughout the body. In individuals with clEDS, these tissues do not function as they should, leading to the syndrome’s distinct characteristics. While symptoms often begin in childhood, many people do not receive a diagnosis until adulthood.
Genetic Roots
Classical-like Ehlers-Danlos Syndrome is caused by genetic variants within the TNXB gene. This gene produces tenascin-X, a protein important for organizing and maintaining connective tissue structure. Tenascin-X helps regulate the production and assembly of collagen, which provides strength and support to tissues.
Harmful genetic changes in both copies of the TNXB gene prevent tenascin-X production. The absence or significant reduction of this protein severely disrupts the organization of collagen fibrils and elastic fibers, leading to weakened connective tissues.
clEDS follows an autosomal recessive inheritance pattern. An individual must inherit a mutated copy of the TNXB gene from both parents to develop the condition. If both parents are carriers, their child has a 25% chance of inheriting clEDS. Individuals who inherit only one mutated copy are symptom-free carriers but can pass the mutation to their offspring.
Key Characteristics
Individuals with classical-like Ehlers-Danlos Syndrome exhibit a distinct set of characteristics, primarily affecting the skin and joints. Skin hyperextensibility is a major feature, meaning the skin can stretch significantly beyond its normal range. This is often accompanied by a velvety skin texture and the absence of atrophic scarring.
Generalized joint hypermobility is another prominent characteristic, indicating that joints have a larger-than-normal range of movement. This can lead to joint instability and recurrent dislocations, most commonly affecting the shoulders and ankles. Easy bruising and spontaneous ecchymoses (discoloration of the skin resulting from bleeding underneath) are also common due to fragile blood vessels and tissues.
Other common symptoms include foot deformities, such as a broad or plump forefoot, flat feet (pes planus), and hallux valgus (bunion). Individuals may also experience mild muscle weakness, affecting both proximal (closer to the body’s center) and distal (further from the center) muscles. Muscle aches and fatigue are also reported.
Nerve issues, such as axonal polyneuropathy (damage to nerve fibers), can also occur, potentially resulting in a loss of sensation. Additionally, individuals with clEDS can be at risk for organ prolapse, where organs like the vagina, uterus, or rectum descend from their normal position.
Path to Diagnosis
The diagnosis of classical-like Ehlers-Danlos Syndrome relies on an evaluation of clinical criteria. A healthcare professional assesses for three major criteria: skin hyperextensibility with a velvety texture and no atrophic scarring; generalized joint hypermobility; and easily bruised skin or spontaneous ecchymoses.
Genetic testing confirms the diagnosis by analyzing DNA for variants in the TNXB gene. This genetic confirmation helps differentiate clEDS from other Ehlers-Danlos syndromes with similar symptoms but different genetic causes.
Consultation with specialists such as geneticists and rheumatologists is part of the diagnostic process. Geneticists interpret genetic test results and explain inheritance patterns. Rheumatologists specialize in joint and connective tissue disorders, offering assessment of musculoskeletal symptoms.
Living with Classical-like EDS
Management of classical-like Ehlers-Danlos Syndrome focuses on addressing each individual’s specific symptoms. Because clEDS can affect multiple body systems, a multidisciplinary approach involving various healthcare providers is often beneficial.
Physical therapy plays a role in strengthening muscles to support unstable joints and improve overall joint stability. Pain management strategies are also used to alleviate chronic pain, which can stem from joint instability and other tissue issues. These strategies may include medications and non-pharmacological interventions.
Regular monitoring for potential organ complications, such as organ prolapse, is part of ongoing care. In some cases, surgical interventions may be necessary to address severe deformities or organ prolapse. Personalized care plans are developed in collaboration with the individual and their care team to meet their specific needs and improve their quality of life.