The Spectrum of Hypermobility

Hypermobility is excess (hyper) movement (mobility) present in the joints of the human body. This is the opposite of hypomobility, the decrease of movement in the joint. Many disorders and diseases diagnosed and managed by Rheumatologists involve hypomobility – the most common being Arthritis. However, thankfully for us, some Rheumatologists are also skilled at managing hypermobility conditions.

Few people know that hypermobility, or this extra movement at the joints, can cause widespread problems for the individual who has inherited this condition. The hypermobile nature of joints can be caused by a range of factors, including the shape of bones and bony articulations, or a training effect. However, it is important to realise that many people with hypermobility actually have problems due to the makeup of the collagen in their bodies.

Collagen is “an insoluble fibrous protein of vertebrates that is the chief constituent of the fibrils of connective tissue (as in skin and tendons)”. The fact that collagen is what makes up connective tissues is how and why we often call hypermobility a ‘connective tissue dysplasia.’ The term ‘connective tissue dysplasia’ (CTD) is used as an inclusive term for over 600 disorders involving problematic connective tissue, including: The Ehlers-Danlos Syndromes, Marfan Syndrome, Loeys-Dietz Syndrome, Osteogenesis Imperfecta (OI), Arthrogryposis, and skeletal bone dysplasias.

There is Hypermobility & there is Symptomatic Hypermobility!

Many people in the world have some level of hypermobility, either caused by bone shape, training/exercise, or through inherited connective tissue disorders.  When you mention the word “hypermobility”, you will often get one of these common responses:

“My friend/daughter/sister is super flexible too – she’s a dancer/gymnast/musician”

“I’m hypermobile too – I roll my ankles and get a sore back”

“What’s that?”

“Oh you mean double-jointed? Me too”

“Oh, isn’t that a good thing?”

“I wish I could do that!”

These types of reactions can be frustrating for people who have significant hypermobility, especially when it is quite disabling and causes both acute and chronic pain. It is best to remember that there is a spectrum of hypermobility, from mild to extreme; you can have hypermobility in one joint, or all your joints; you can have asymptomatic hypermobility, or you can have a hypermobility spectrum disorder. There are many variations, making it hard to compare the impacts of being hypermobile. And do you know what? Comparing isn’t going to get us anywhere anyway! Empathy is one thing, comparison is another.

Health professionals will use the Beighton Scale to get an indication of how widespread a person’s hypermobility is, and often this gives an impression of how significant/ problematic it is too. However, you can have a high Beighton Score and not have symptoms (e.g. pain, fatigue, dislocations) – for reasons we are still discovering.

The Hypermobility Spectrum Disorders

From March 2017, we are working with the new classification system decided upon by the International Consortium on the Ehlers-Danlos Syndromes.

That new classification brings with it a review of the hypermobility disorders, with hypermobility syndrome now renamed, and falling under the umbrella of Hypermobility Spectrum Disorders. This spectrum of joint hypermobility now includes:

Asymptomatic Generalised Joint Hypermobility

Asymptomatic Peripheral Joint Hypermobility

Asymptomatic Localized Joint Hypermobility

Generalised Hypermobility Spectrum Disorder

Peripheral Hypermobility Spectrum Disorder

Localized Hypermobility Spectrum Disorder

Historical Hypermobility Spectrum Disorder

Taken from: A framework for the classification of joint hypermobility and related conditions (Castori et al, 2017)

Generalized (joint) HSD (G-HSD): GJH objectively assessed (e.g., by the Beighton score) plus one or more secondary musculoskeletal manifestations as previously identified. In these patients, the pattern and severity of the involvement of the musculoskeletal system should be carefully assessed in order to explore the possibility of a full-blown hEDS. In this category usually fall most patients with GJH and additional musculoskeletal manifestations but do not meet the full diagnostic criteria for hEDS.

Peripheral (joint) HSD (P-HSD): JH limited to hands and feet plus one or more secondary musculoskeletal manifestations as previously identified.

Localized (joint) HSD (L-HSD): JH at single joints or group of joints plus one or more secondary musculoskeletal manifestations regionally related to the hypermobile joint(s).

Historical (joint) HSD (H-HSD): self-reported (historical) GJH (e.g., by the five-point questionnaire) with negative Beighton score plus one or more secondary musculoskeletal manifestations as previously identified; in these cases, physical examination aimed at excluding the alternative diagnoses of G-HSD, P-HSD, and L-HSD as well as other rheumatologic conditions is mandatory.

The secondary musculoskeletal manifestations that can occur in HSDs include:

  • joint trauma (e.g. micro & macro trauma from subluxations, dislocations, sprains etc.)
  • pain
  • degenerative joint and bone disease
  • neurodevelopmental differences (e.g. disturbed proprioception, muscle weakness); and
  • orthopaedic traits

SUMMARY:

Joint Hypermobility (JH) is characterised by an excessive range of movement at a joint in the body.

You can have asymptomatic joint hypermobility, that is, hypermobility in the joints which do not cause any musculoskeletal complaints.

Hypermobility Spectrum Disorders is the term that encompasses Generalised, Peripheral, Localised and Historical Hypermobility Spectrum Disorders.

The Beighton Scale is used to determine the level of generalised hypermobility. Otherwise, in individuals whose ability to perform the Beighton Scale, the Five-Point Questionnaire is used.

There is a range of different conditions which can cause hypermobility of the joints, of which Hypermobility Spectrum Disorders and Hypermobile EDS are just two.

The Ehlers-Danlos Syndromes

As a result of the International EDS Symposium in 2016, we now have new diagnostic criteria for the Ehlers-Danlos Syndromes. There are now 13 types of Ehlers-Danlos Syndrome, giving rise to the change in terminology to ‘The Ehlers-Danlos Syndromes’.

Not all types of Ehlers-Danlos Syndrome have generalised joint hypermobility (GJH) as a major feature. Types are marked with *major or *minor to indicate importance of hypermobility in criteria.

Classical EDS (cEDS)

Genetic Basis: Major: COL5A1, COL5A1; Rare: COL1A1 Protein: Type V Collagen, Type I Collagen *major for hypermobility

Classic-like EDS (clEDS)

Genetic Basis: TNXB Protein: Tenascin XB *major for hypermobility

Cardiac-valvular (cvEDS)

Genetic Basis: COL1A2 (biallelic mutations that lead to COL1A2 NMD and absence of pro α2(I) collagen chains) Protein: Type I Collagen *major for hypermobility

Vascular EDS (vEDS)

Genetic Basis: Major: COL3A1;  Rare: COL1A1 Protein: (major) Type III Collagen; (rare) Type I Collagen *minor for hypermobility

Hypermobile EDS (hEDS)

Genetic Basis: Unknown Protein: Unknown *major for hypermobility

Arthrochalasia EDS (aEDS)

Genetic Basis: COL1A1, COL1A2 Protein: Type I Collagen *major for hypermobility

Dermatosparaxis EDS (dEDS)

Genetic Basis: ADAMTS2 Protein: ADAMTS2 *minor for hypermobility

Kyphoscoliotic EDS (kEDS)

Genetic Basis: PLOD1 ; FKBP14 Protein: LH1 ; FKBP22 *major for hypermobility

Brittle Cornea syndrome (BCS)   

Genetic Basis: ZNF469 Protein: ZNF469 *minor for hypermobility

Spondylodysplastic EDS (spEDS)

Genetic Basis: B4GALT7 ; B3GALT6 ; SLC39A13 Protein: β4GalT7 ; β3GalT6 ; ZIP13 *minor for hypermobility

Musculocontractural EDS (mcEDS)

Genetic Basis: CHST14 ; DSE Protein: D4ST1 ; DSE

Myopathic EDS (mEDS)  

Genetic Basis: COL12A1 Protein: Type XII Collagen *major for hypermobility

Periodontal EDS (pEDS)  

Genetic Basis: C1R ; C1S Protein: C1r; C1s *minor for hypermobility

Loeys-Dietz Syndrome

Loeys-Dietz syndrome is a disorder that affects the connective tissue in many parts of the body. Connective tissue provides strength and flexibility to structures such as bones, ligaments, muscles, and blood vessels.

There are five types of Loeys-Dietz syndrome, which are distinguished by their signs and symptoms.

The signs and symptoms of all types of Loeys-Dietz syndrome can become apparent anytime from childhood into adulthood. The aortic problems associated with Loeys-Dietz syndrome can be fatal by mid to late adulthood.

There is a great resource from the Loeys-Dietz Syndrome Foundation Canada called Head to Toe that may be useful in exploring signs & symptoms of Loeys-Dietz Syndrome

TYPE I:  Loeys-Dietz syndrome type I is characterized by enlargement of the aorta, which is the large blood vessel that distributes blood from the heart to the rest of the body. The aorta can weaken and stretch, causing a bulge in the blood vessel wall (an aneurysm). Stretching of the aorta may also lead to a sudden tearing of the layers in the aortic wall (aortic dissection). People with Loeys-Dietz Syndrome Type I may have other kinds of heart defects. These individuals can also have aneurysms or dissections in arteries throughout the body and have arteries with abnormal twists and turns (arterial tortuosity). Other characteristic features of Loeys-Dietz syndrome type I include widely spaced eyes (hypertelorism), a split in the soft flap of tissue that hangs from the back of the mouth (bifid uvula), and an opening in the roof of the mouth (cleft palate). People with this condition may bruise easily and develop abnormal scars after wound healing. Affected individuals may also have skeletal problems including premature fusion of the skull bones (craniosynostosis), an abnormal side-to-side curvature of the spine (scoliosis), either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum), an inward- and upward-turning foot (clubfoot), or elongated limbs with joint deformities (contractures), that restrict the movement of certain joints. OMIM #609192
TYPE II: Loeys-Dietz syndrome type II has features that overlap with those of type I, such as enlargement of the aorta and other arteries and arterial tortuosity. But other features of type I, such as skeletal signs, are typically less severe or absent in type II. People with Loeys-Dietz syndrome type II have skin abnormalities, such as velvety skin that is sometimes described as translucent, often with the underlying veins visible. As in type I, people with type II bruise easily and have abnormal scarring. OMIM #610168
TYPE III:  The main features of Loeys-Dietz syndrome type III are aortic and arterial aneurysms and dissections, along with joint pain (osteoarthritis) that typically becomes apparent in early to mid-adulthood. The joints most commonly affected are the joints of the hands, wrists, knees, and spine. Because of these characteristic features, Loeys-Dietz syndrome type III is sometimes referred to as aneurysm-osteoarthritis syndrome. Other signs and symptoms of Loeys-Dietz syndrome type III include the breakdown (degeneration) of the discs that separate the bones of the spine (vertebrae) from each other, scoliosis, and flat feet (pes planus). People with type III can also have skeletal, facial, and skin features that overlap with those of Loeys-Dietz syndrome types I and II. OMIM #613795
TYPE IV: See  OMIM #614816
TYPE V: See OMIM #615582

Marfan Syndrome

This information was taken directly from The Marfan Foundation 

People are born with Marfan syndrome and related disorders, but they may not notice any features until later in life. However, features of Marfan syndrome and related disorders can appear at any age. Some people have many features at birth or as young children. Other people develop features, including aortic enlargement, as teens or even as adults.  Some features are progressive, meaning they can get worse as people age.

All of this makes it very important for people with Marfan syndrome and related disorders to have ongoing monitoring, especially for life-threatening aspects of the condition like aortic enlargement. An accurate and early diagnosis helps to ensure proper treatment. Some treatments can prevent symptoms from getting worse and ultimately save lives.

Some signs are easy to see

Every person’s experience with Marfan syndrome is slightly different. No one has every feature and people have different combinations of features. Some features of Marfan syndrome are easier to see than others. These include:

  • Long arms, legs, and fingers
  • Tall and thin body type
  • Curved spine
  • Chest sinks in or sticks out
  • Flexible joints
  • Flat feet
  • Crowded teeth
  • Stretch marks on the skin that are not related to weight gain or loss

 

Other signs are harder to detect

Harder-to-detect signs of Marfan syndrome include heart problems, especially those related to the aorta, the large blood vessel that carries blood away from the heart to the rest of the body. Other signs can include sudden lung collapse and eye problems, including severe nearsightedness, dislocated lens, detached retina, early glaucoma, and early cataracts. Special tests are often needed to detect these features.

What does Marfan Syndrome look like?

Marfan syndrome can affect many parts of the body, and each person is affected differently. This is called variable expression. Features can even vary among people in the same family who have the condition. Visit our photo gallery to see the many faces and body types of Marfan syndrome. (The Marfan Foundation)