The problems present in the group of disorders known as Ehlers-Danlos syndrome (EDS) include changes in the physical properties of skin, joints, blood vessels, and other tissues such as ligaments and tendons. Mutations in several different genes are responsible for varying symptoms in the several types of Ehlers-Danlos syndrome. In most cases, the genetic defect involves collagen, the major protein-building material of bone.
Signs vary widely based on which type of EDS the patient has. In each case, however, the signs are ultimately due to faulty or reduced amounts of collagen. EDS typically affects the joints, skin, and blood vessels. Following is a list of major signs and symptoms.
- Hyper-flexible joints (It is possible to be very flexible or have “double joints”, however, this is not the same as EDS.)
- Unstable joints that are prone to: sprain, dislocation, subluxation and hyperextension
- Early onset of advanced osteoarthritis
- Chronic degenerative joint disease
- Swan neck deformity of the fingers
- Muscle fatigue that increases with use
- Weak muscle tone (hypotonia) in infancy, which can delay the development of gross motor skills such as sitting, standing, and walking
- Osteopenia (low bone density)
- Stretchy ligaments and tendons
- Tearing of tendons or muscles
- Deformities of the spine, such as: Scoliosis (curvature of the spine), Kyphosis (a thoracic hump), Tethered spinal cord syndrome, Occipitoatlantoaxial hypermobility
- Myalgia (muscle pain) and arthralgia (joint pain), which may be severe
- Trendelenburg’s sign
- Stretchy skin with a velvety texture
- Fragile skin that tears easily
- Easy bruising, which can be severe
- Abnormal wound healing and scar formation, leading to widened atrophic scars
- Redundant skin folds
- Molluscoid pseudotumors, especially on pressure points
- Subcutaneous spheroids
- Fatty growths on forearms or shins
- Fragile blood vessels with tendency towards aneurysm including abdominal aortic aneurysm
- Life-threatening carotid-cavernous fistula
- Unpredictable rupture of medium-sized arteries, especially cerebral arterial rupture
- Valvular heart disease (such as mitral valve prolapse, which creates an increased risk for infective endocarditis during surgery, as well as possibly progressing to a life-threatening degree of severity of theprognosis of mitral valve prolapse)
- Postural orthostatic tachycardia syndrome (P.O.T.S.)
- Orthostatic intolerance, theoretically caused by excessive distension of veins (upright posture causes blood pooling in lower body, leading to a 44–60% decrease in cerebral blood flow velocity
- Dilation and/or rupture of ascending aorta
- Cystic medial necrosis
- Varicose veins
- Vascular skin conditions: Raynaud’s phenomenon, Livedo reticularis
Other manifestations or complications:
- High and narrow palate, resulting in dental crowding
- Early-onset periodontitis
- Nearsightedness, which may be extreme
- Blue sclera
- Retinal detachment
- Flat feet
- Digestive disorders: (gastritis, gastroesophageal reflux disease, irritable bowel syndrome, diverticulitis, gastroparesis (partial paralysis of the stomach))
- Hiatial hernia
- Anal prolapse
- Vulnerability to chest and sinus infections
- Collapsed lung (pneumothorax)
- Intestinal/uterine fragility or spontaneous rupture
- Nerve compression disorders (carpal tunnel syndrome, acroparesthesia, neuropathy)
- Anxiety disorders, depression, psychosocial dysfunction
- Insensitivity to local anesthetics.
- Arnold–Chiari malformation (brain disorder)
- Cranial instability
- Problems with concentration and/or memory
- Problems with proprioception including dysmetria
- Talipes equinovarus (club foot), especially in the Vascular type
- Platelet aggregation failure (platelets do not clump together properly)
- Bleeding diathesis
- Cerebrospinal fluid leak (rent in the meningeal tissues: dura, arachnoid)
- Temporomandibular joint syndrome
- Surgical complications and intraoperative problems due to tissue fragility
- Pregnancy complications: increased pain, mild to moderate peripartum bleeding, cervical insufficienty, uterine tearing, or premature rupture of membranes.
Because it is often undiagnosed or misdiagnosed in childhood, some instances of Ehlers–Danlos syndrome have been mischaracterized as child abuse. The pain associated with this condition is a serious complication.
A diagnosis can be made by an evaluation of medical history and clinical observation. The Beighton criteria are widely used to assess the degree of joint hypermobility. Both DNA and biochemical studies can be used to help identify affected individuals. Diagnostic tests include: collagen gene mutation testing, collagen typing via skin biopsy, echocardiogram, and lysyl hydroxylase or oxidase activity. However, these tests are not able to confirm all cases, especially in instances of an unmapped mutation, and so clinical evaluation by a geneticist remains essential. If there are multiple affected individuals in a family, it may be possible to perform prenatal diagnosis using a DNA information technique known as a linkage study
Common surgical procedures are joint debridement, tendon replacements, capsulorraphy and arthroplasty. Studies have shown that after surgery, degree of stabilization, pain reduction, and patient satisfaction can improve, but surgery does not guarantee an optimal result and both patients and surgeons report being dissatisfied with the results. Consensus is that conservative treatment is more effective than surgery, particularly since patients with Ehlers-Danlos Syndrome have extra risks of surgical complications due to the disease. Three basic surgical problems arise due to EDS: the strength of the tissues is decreased, which makes the tissue less suitable for surgery; the fragilty of the bloodvessels can cause problems during surgery; and wound healing is often delayed or incomplete. Studies have shown that local anesthetics, arterial catheters and central venous catheters cause a higher risk in haematoma formation in patients with Ehlers-Danlos Syndrome. Ehlers-Danlos patients also show a resistance to local anasthaetics.
Surgery with Ehlers-Danlos patients requires careful tissue handling and a longer immobilization afterwards. Because local anasthetics have less effect, k-wires often can’t be removed afterwards and should not be used.
The outlook for individuals with EDS depends on the type of EDS with which they have been diagnosed. Symptoms vary in severity, even within one sub-type, and the frequency of complications changes on an individual basis. Some individuals have negligible symptoms while others are severely restricted in their daily life. Extreme joint instability, chronic musculoskeletal pain, degenerative joint disease, frequent injuries, and spinal deformities may limit a person’s mobility. Severe spinal deformities may affect breathing. In the case of extreme joint instability, dislocations may result from simple tasks such as rolling over in bed or turning a doorknob. Secondary conditions such as autonomic dysfunction or cardiovascular problems, occurring in any type, can affect prognosis and quality of life. Severe mobility-related disability is seen more often in Hypermobility-type than in Classical-type or Vascular-type.
Although all types are potentially life-threatening, the majority of individuals will have a normal lifespan. However, those with blood vessel fragility have a high risk of fatal complications. Arterial rupture is the most common cause of sudden death in EDS. Spontaneous arterial rupture most often occurs in the second or third decade, but can occur at any time. The average life-expectancy for Vascular EDS is 48 years.
EDS is a lifelong condition. Affected individuals may face social obstacles related to their disease on a daily basis. Some people with EDS have reported living with fears of significant and painful ruptures, their condition worsening, becoming unemployed due to physical and emotional burdens, and social stigmatization in general.