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Epidemiology

Joint Hypermobility Syndrome (JHS) is a largely under-recognized and poorly understood multi-systemic hereditary connective tissue disorder which manifests in a variety of different clinical presentations. Also termed heritable disorder of connective tissue (HDCT), this is a heterogeneous group of genetically determined diseases, with JHS being a milder variation of Ehlers-Danlos Syndrome (EDS), where gross joint laxity often prevails. While hypermobility is a feature common to them all, they are all believed to be caused by a defect in collagen, the essential connective tissue protein responsible for tensility and integrity of skin and joints tissues.^{1, 2}

While Ehlers-Danlos Syndrome is the most severe form of hypermobility, many others suffer from similar conditions such as JHS, or even benign or undiagnosed forms of hypermobility, which present many of the same characteristics as EDS. Studies have indicated that JHS affects 2%–5% of the general population, although it is estimated that 1 in 20 hypermobile patients have not been diagnosed for their disorder.^{3, 4} EDS is collectively believed to affect one in every 5000 children at time of birth, although this number is a rough estimate due to the fact that EDS is widely underdiagnosed in the general population.^{5, 6} At present, there are six primary known classifications of EDS: Classic, Hypermobility, Vascular, Kyphoscoliosis, Arthrochalasia, and Dermatosparaxis (See Figure 1.) The hypermobility type, which is found to be the most common, is estimated to affect one in every 10,000 to 15,000 individuals.⁷

ETIOLOGY AND PATHOLOGY

JHS has a strong genetic component with an autosomal dominant pattern. First-degree relatives with the disorder can be identified in as many as 50% of cases. Within this population, statistics indicate that EDS is more prevalent in those of African, Asian, and Middle Eastern descent, and affects women significantly more than men.^8-10 The syndrome appears to be due to an abnormality in collagen or in the ratio of collagen subtypes. Mutations in the fibrillin gene have also been identified in families with JHS.^{11, 12}

Ehlers-Danlos Syndrome is caused by defects in the biogenesis of collagen, the major structural protein of the body. The condition can be either inherited from a parent with the defect or caused by a genetic mutation. EDS is generally inherited in an autosomal dominant pattern, though an autosomal recessive type exists. Mutations in genes encoding fibrillar collagens or collagen-modifying enzymes have been identified in most forms of EDS, including the classic and vascular subtypes. To date, the genetic background of the hypermobility type of EDS remains unclear. The exact gene involved in hypermobility type EDS is unknown, although research indicates that there may be a connection to haploinsufficiency (having less than one half of the necessary amount) of tenascin X which is encoded by the gene TNXB.¹³ Family history is an important tool in diagnosing EDS, because first-degree relatives have about a fifty percent chance of inheriting the defect.¹⁴ Unfortunately, there is no prenatal method of testing available to determine whether or not the defect has been passed down to a child.

When a defect such as the one found in EDS is present, collagen fibers become weakened, allowing tissues to become more elastic. In more severe cases, such as vascular type EDS, this can affect the tissues of the internal organs, such as the abdominal aorta, colon, and brain vessels, causing them to become weak and even rupture under pressure.¹⁵ In the case of JHS and hypermobility type EDS, the weakened collagen fibers affect the integrity of ligaments in the joints, and ultimately the stability of the joint. The weakness of these ligaments is what allows joints to hyperextend beyond the normal physiological limits.

Joint hypermobility, a key finding in the heritable disorders of connective tissues, is diagnostically evaluated according to the Brighton Criteria, which utilizes the Beighton Score.^** Determining the Beighton score is essential for making the diagnosis of JHS because it measures generalized joint laxity. The Beighton Score measures the ability to perform certain hyperextensive functions, including significant flexion of the thumb and fifth finger, hyperextension of both knees and elbows greater than 10 degrees, and the ability to place the palms on the floor with the knees fully extended, by assigning a point to each of these functions. (See Figure 2.) The Brighton criteria were developed to establish diagnostic criteria for JHS. Using these criteria helps physicians to distinguish JHS from other connective tissue disorders.16 According to the Brighton criteria, a score of four or higher on the Beighton Scale indicates generalized joint laxity and this along with athralgia in four or more joints for longer than three months signifies joint hypermobility syndrome.^17,18 (See Figure 3.) Typically a score of five or higher on the Beighton Scale is used as the cut-off for Ehlers-Danlos Syndrome.^**

Figure 1. The six primary known classifications of Ehlers-Danlos Syndrome (EDS).

Readers should not be confused by the similarity of
these two names. “Beighton” is the name of the score,
and “Brighton” is the name of the criteria.

Figure 2. Beighton 9-point scoring system for joint hypermobility. A score of 4 or greater is indicative of generalized joint hypermobility.

Figure 3. Brighton Criteria for Joint Hypermobility Syndrome. Keer R and Grahame R. Hypermobility syndrome: recognition and management for physiotherapists. London: Butterworth Heinemann; 2003.

^** There is still some debate on the necessary criteria for making the diagnosis of Ehlers-Danlos Syndrome (EDS). While a Beighton score of 5 is indicative of EDS, a score of 4 does not preclude the diagnosis. Most agree that the diagnosis is made by a family history of the condition and the clinical evaluation. Genetic testing and muscle and skin biopsies confirm the connective tissue (collagen) disorder. Other diagnostic testing such as echocardiogram, MRIs and CT scans can be used to confirm blood vessel, valvular, and organ connective tissue problems seen in the various types of EDS.