The average person has never heard of connective tissue, but it’s practically everywhere in your body — from your skin to your eyes to your heart. So what is it? Connective tissue provides elasticity, structure and metabolic support to numerous organs, joints and other bodily structures. It binds, separates and supports the tissues of your muscles, nervous system and more. 

Because this tissue is so prevalent, a broad range of symptoms and complications can arise when problems occur in the structure, function or regulation of your connective tissue. Connective tissue disorders can result from autoimmune or genetic conditions. Autoimmune conditions generally develop later in life, while genetic disorders usually result from specific genes or genetic mutations you were born with. Either way, connective tissue disorders can significantly influence quality of life and often require long-term management and treatment. 

Signs of a Genetic Connective Tissue Disorder

Inherited connective tissue disorders can impact many body parts, including the skin, muscles, joints and bones. Symptoms vary widely depending on the condition and affected individual, with some of the most universal features described below.  

  • Joint Hypermobility: Many patients experience excessive joint flexibility or hypermobility and are prone to dislocations or injuries.
  • Skin Abnormalities: Individuals may have skin with unusual hyperelasticity (stretchiness), easy bruising, thinness or translucence, and slow wound healing.
  • Joint Pain: Patients may have persistent or recurrent joint pain, which may be associated with joint inflammation or stiffness.
  • Muscle Weakness: Frequent or ongoing muscle weakness or fatigue may occur, especially in disorders involving muscle inflammation.
  • Cardiovascular Abnormalities: Some connective tissue disorders, such as Marfan syndrome, are linked to cardiovascular issues, including aortic aneurysms, mitral valve prolapse or other heart-related complications.
  • Eye Abnormalities: Vision problems, myopia (nearsightedness) and other eye abnormalities may be present in connective tissue disorders.
  • Gastrointestinal Issues: Individuals with connective tissue disorders can experience gastrointestinal symptoms, such as acid reflux or digestion problems.
  • Skeletal Abnormalities: Some disorders lead to deformities in the spine (such as scoliosis or kyphosis), hands, feet, ankles or face. Individuals may also be unusually short or tall.
  • Unexplained Fatigue: Patients may have chronic fatigue or weakness unexplained by other medical conditions.

Examples of Genetic Connective Tissue Disorders

The medical community has identified over 200 genetic connective tissue disorders. Here are a few of the most common.

Ehlers-Danlos Syndrome (EDS): Ehlers-Danlos Syndrome is a group of genetic disorders affecting the connective tissues, particularly collagen. Over a dozen subtypes of EDS exist, each associated with specific genetic mutations. Features frequently include hypermobility of joints, skin that is easily bruised and hyper-elastic and tissue fragility. Complications vary by subtype, with the possibility of recurring joint injuries, early-onset arthritis, difficulty healing wounds and potentially fatal blood vessel ruptures.

Marfan Syndrome: Marfan syndrome results from mutations in the FBN1 gene, which encodes fibrillin-1, a component of connective tissue. Individuals with Marfan syndrome may have long limbs, fingers, and toes, tall height, lens dislocation, nearsightedness, cardiac problems and a chest that sticks out or sinks in. This disorder can also impact the lungs and skin.

Loeys-Dietz Syndrome: This syndrome is also associated with heart problems, including an enlarged aorta and heart valve defects. Many individuals with Loeys-Deitz syndrome have a characteristic facial appearance, often with a small chin and eyes that are widely spaced or have a downward slant. They may have skin, vision and musculoskeletal abnormalities.

Stickler Syndrome: Stickler syndrome involves mutations in genes such as COL2A1, COL11A1, COL11A2 and COL9A1, affecting collagen in the connective tissues. It is associated with hearing loss, facial abnormalities and joint problems. Many individuals with Stickler syndrome also experience extreme nearsightedness.

Osteogenesis Imperfecta (OI): OI is primarily caused by mutations in genes involved in collagen synthesis, particularly COL1A1 and COL1A2. It leads to brittle bones that break easily and may affect other connective tissues.

Diagnosing and Managing Genetic Connective Tissue Disorders

Patients with connective tissue disorders may struggle with symptoms for years before receiving a complete or accurate diagnosis. They may have had multiple hospital visits, MRIs, ultrasounds, and tests, but no clear unifying explanation. Genetic evaluations can help these patients find answers. If you or a family member have also experienced symptoms of a connective tissue disorder, consider seeing a genetic counselor and medical geneticist for a consultation. A definitive diagnosis often requires genetic testing and analysis.

Once diagnosed, managing a connective tissue disorder typically requires a multidisciplinary approach. Testing can provide valuable information on how the disorder may progress or manifest over time. This information can help your care team develop a personalized monitoring and care plan. It can also allow patients to make informed decisions for family planning.

Depending on the manifestations of the disorder, healthcare professionals such as geneticists, cardiologists, gastroenterologists and other specialists should collaborate closely to monitor and support patients. Together, they can offer proactive care to mitigate risk and identify potential issues early before they worsen. Treatment may include medications, physical therapy, clinical trials and lifestyle modifications to manage symptoms and improve overall well-being. 

At Sequence MD, we want to help you find answers to your health questions and get the personalized care you need. To talk with the clinical genetics team at SequenceMD about your symptoms and concerns, get in touch today.