Dr. Russell received her fellowship in rheumatology from the University of North Carolina at Chapel Hill. She is currently doing academic medicine at the medical college of Milwaukee, Wisconsin. She is interested in further work with vascular EDS.

 
One of the cardinal features of the Ehlers-Danlos Syndromes (EDS) is joint hypermobility. The presence or absence of hypermobility is determined at the bedside and is largely the result of subjective and semi-objective comparison of range of motion at selected joints to that considered “normalâ€�.  In addition, many different factors contribute to motion that may be designated as “hypermobileâ€�. However, whether the particular patients’ hypermobility results in symptoms or not cannot be assessed from the physical exam alone. Lastly, the patient I see at 9 o'clock with hypermobility probably has a different molecular abnormality than the patient I see at 10 o'clock with hypermobility.  It is therefore useful to keep in mind that EDS is indeed a heterogeneous group of disorders  and the molecular basis for the problems that we see in the clinic are probably individual or familial and not the same from patient to patient.

What causes hypermobility? What are the constraints in normal joint motion?  What prevents our joints from moving in all directions? The motion of any particular joint has evolved to subsume a particular function for the human who must also negotiate the effects of gravity during their lifetime.  There are many factors that have an effect on what motion is allowed at any particular joint under normal conditions. Consideration of these factors will enable the physician to establish an accurate understanding of the problem in any particular patient.

Joint hypermobility and joint laxity are terms that are used commonly to describe a recognized increase in joint range of motion.  Hypermobility is commonly used to mean that the range of motion of a joint exceeds normal but does not necessarily impact on the patient in terms of stability or symptoms. The "normal"� range of motion is age and ethnic dependent.  Children are uniformly more hypermobile than adults. In the adult, the hypermobile patient may or may not have any pain or history of subluxations and dislocations. Given these caveats, it can be difficult to determine if a patient is truly hypermobile or not. We know that hypermobility is very common in Indian populations and the entire population of Egypt is extremely hypermobile.  Are these people abnormal?  No, if they don't have symptoms.  It simply means their range of motion is different than that of Caucasians.  So when approaching a particular patient, the physician must decide whether this hypermobility is related to ethnicity and is physiologic or not.  Sometimes this can be difficult since there are few objective guidelines to employ.  Standardized measurements that create a numerical correlate to the degree of hypermobility, such as the Beighton score, can be quite useful in this setting. 

Laxity refers to something beyond the normal range of motion but implies a predisposition to subluxations; the distinction is subtle and not always made and the terms are often used synonymously. At the extreme of laxity, one begins to observe pathologic range of motion.  Instability is laxity that results in joint dysfunction and instability is involuntary.  Voluntary and then involuntary subluxations may develop and, finally, dislocation of the joint altogether.  There is a continuum from one to the other. The presence or absence of pain during this evolution will depend on the degree of injury to adjacent nerve-containing structures such as the joint capsule. Often this will depend on the speed of development of the instability with acute disruptions and instability being the most likely to coincide with pain.

In approaching the patient, the physician must decide if they have simple hypermobility or whether, in fact, the patient is having subluxations and true instability of the joint. In either case, the doctor must understand the process by which the unusual motion is occurring in that patient.  Joints exist in our body to provide movement but there are a lot of normal constraints to joint motion that need to be considered. First of all, the contours of the bone make a difference as to how much joint motion is going to be allowed.  There is a very tight fibrous capsule that holds the bone ends together in all of the joints in our body.  That has a big effect on how much motion is allowed.  Some joints of our body, for example, the knee, the temporo- mandibular joint, and other joints in the body have a little pad inside called a meniscus, a fibrocartilage that helps distribute force and also constrains the motion to some extent. Ligaments are very useful to limit a joint's motion and these are fibrous bands that connect bones together across joint lines.  Ligaments often blend into the tendons that are in that area.  Tendons also help limit motion as do the muscles overlying the joints.  The soft tissues around the joint in question also impact the motion and gravity itself contributes a significant force. Lastly, the nerve supply to a joint is imperative to the body's balanced use of adjacent muscles and abnormal proprioception is known to result in dynamic instability.

Every time a physician approaches a patient who is hypermobile, the integrity of all these tissues needs to be kept in mind to accurately diagnose the cause of the hypermobility or instability. Bone contours are difficult to assess at the bedside but important as a potential cause of hypermobility and subluxations.  One can have damage to bone ends that will alter the contours and some joints inherently have more bone constraint than others.   For instance, the hip is a ball and socket joint and has a lot of bone constraint as to how much motion is to be allowed, the shoulder has almost none; it is held together by soft tissues. Congenital malformation of the bone ends, even subtle ones, are increasingly recognized in subsequent mid-age development of degenerative arthritis and this is felt to be secondary to asymptomatic low-level instability.  For example, the socket part of the bone for the hip may be somewhat shallow and this would allow the head of the femur to move within the joint capsule a little more than usual.  Bony contour abnormalities are very common and doctors have to be careful when they are interpreting hypermobility at a joint that it is not actually because of a change in the normal shape of the bone. 

The capsule is a very important feature in constraining motion.  It has been estimated that about 40% to 50% of joint motion is constrained by the capsule of the joint.  Capsules have very few elastic fibers and are very tight fibrous tissues. If a capsule is torn because of injury, the capsule will no longer have the same integrity.  The loss of fiber strength may thereafter allow more motion than before the trauma and so the joint becomes "hypermobile"�.  So, in approaching a patient with just 2 or 3 hypermobile joints, the physician has to be very careful that they are not missing an anatomic disturbance that is causing the laxity as opposed to a congenital collagen defect like EDS.  EDS is a group of disorders where the physical properties of this capsule are abnormal and diffuse stretching occurs during routine use of the joints.  The capsule does not have much recoil, so if the patient repeatedly stretches the capsule, eventually the distention will not be reversible. However, in contrast to the post-traumatic joints, the resulting hypermobility will be widespread and symmetric since the inherited defect is throughout. These concerns apply also to the intraarticular fibrocartilage meniscus found in some joints which acts to disperse forces and to control motion of the bone ends.  Tearing or distortion of these tissues may result in permanently hypermobile or unstable joints.

Outside of the joint, the bulk of the overlying muscles will affect how much a person can move a joint.  The contribution of muscles to the constraint of joint motion is very large and is estimated to be about 30% or more. Some of this effect is due to spatial interference because if the muscle is bigger, the bulk itself will interfere with motion of the joint.  But, most of all, the tone of the adjacent muscles is going to help hold the bone ends together.  The more tone you have, the tighter the muscle's pull on the adjacent bones. This results in less likelihood that the bone ends are going to move beyond their normal range.  This is particularly evident in people with EDS in the gravity affected lower extremity joints. At nighttime, when the muscles relax, patients with EDS may experience subluxations in knees, spine, and hips.  Lastly, it has been suggested that patients with some forms of EDS have an abnormality in the muscles themselves.  They postulate that muscles from such patients always have poor tone (hypotonia) and that this chronically contributes to the hypermobility. The cause of such muscle dysfunction is unknown. The compliance (the flexibility) of the connective tissues adjacent to the joint also plays a part.  One disease known as scleroderma is associated with increased collagen production, increased thickness in the skin, and patients complain that they cannot move their joints very well. They notice that joints are indeed stiff.  The joints themselves may be structurally normal.  However, because the overlying dermis and sub-dermis are tightened, they really cannot move their joints very well.  The converse is true in EDS where the skin is often thin or where the subdermal fat content is decreased.  The thin, extensible connective tissues in the skin and fat layers change the compliance of these tissues adjacent to the joints.  Thus the increased flexibility provides decreased resistance to movement. 

How do physicians examine a patient and decide whether or not the patient has joint hypermobility or instability?   The physical examination at the bedside is still the best way of assessing whether there is hypermobility.  Passive range of motion testing, where the doctor guides the joint without the patient exerting effort, tests the range of arc attainable.  Such a bedside exam can be done on all joints but demands that the physician take care not to sublux or dislocate a joint that is unstable during maneuvers where the patient has been asked to refrain from protective splinting. The capsular distensibility is tested by distraction of the joint and the excursion of the bone ends gives a subjective assessment as to unusual capsule laxity.  Muscle bulk and tone are separately assessed. This requires some experience on the part of the examiner for accurate interpretation. A Beighton score will give some estimate of the overall hypermobility but the distribution of joints involved can help with phenotyping EDS.  Instability, however, requires demonstration of loss of articular surface congruity so that the bone ends can be shown to have moved away from normal position.  This can be demonstrated at the bedside in peripheral joints but may need X-rays to confirm positions in the hips, shoulders, and spine in particular.

Imaging is needed to evaluate a joints' meniscal status but single-view X-rays and MRIs are generally poor tools to evaluate chronic instability where alignment at rest may be normal.  Sequential view X-rays, however, can often detect instability in axial (spinal) joints when the physical exam is equivocal.  The doctor is then looking for "slippage" of one bone over another at the extremes of motion that suggests instability. In addition, recurrent dislocations in a joint will result in changes in the adjacent bones over time and this can be detected as a thumbprint of long-standing instability. X-rays can also be used to see if there is a congenital deformity of bone ends predisposing to hypermobility at that joint. Acute capsule and ligament tears, however, are usually demonstrated by MRI which gives a clear picture of major soft tissue disruption.
 Other studies that may be useful include ultrasound which can be used real-time to detect soft tissue instability (tendon subluxations, etc.) It is not yet used routinely to study joint hypermobility per se.  Arthrograms (where dye is injected into the joint) are useful to examine structural integrity of intraarticular structures but are not good to diagnose hypermobility. A nerve conduction study can assess if the nerves supplying a joint and muscles responding are working properly. In the future, dynamic imaging, where images of something are done during motion, will undoubtedly be further developed and this will enable diagnosis of hypermobility and instability on a more objective basis.  Such imaging may allow anatomic clarification of the mechanism behind the laxity as well.  Also, DNA analysis of the patient may be able to pinpoint the molecular defect quickly and this may allow a targeted approach to repair or compensation for the defect locally.