Hypermobile Ehlers-Danlos syndrome

Although hypermobile Ehlers-Danlos syndrome is regarded as a genetic condition, the underlying cause (gene or genes responsible) has not been identified.

Hypermobile Ehlers-Danlos syndrome (hEDS) is diagnosed based on the presence of characteristic signs and symptoms because there is no specific test available. The following three major criteria should be met:

Criteria 1 : Generalized joint hypermobility (small and large joints) which is assessed by using the Beighton Score system and a questionnaire.

Criteria 2 : Two or more of the following features must be present (A&B, A&C, B&C, or A&B&C):

Feature A —systemic manifestations of a more generalized connective tissue disorder (a total of 5 out of 12 must be present)

1. Unusually soft or velvety skin
2. Mild skin hyperextensibility
3. Unexplained striae such as striae distensae or rubrae at the back, groins, thighs, breasts and/or abdomen in adolescents, men or prepubertal women without a history of significant gain or loss of body fat or weight
4. Bilateral piezogenic papules of the heel
5. Recurrent or multiple abdominal hernia(s) (e.g., umbilical, inguinal, crural)
6. Atrophic scarring involving at least two sites and without the formation of truly papyraceous and/or hemosideric scars as seen in classical EDS
7. Pelvic floor, rectal, and/or uterine prolapse in children, men or nulliparous women without a history of morbid obesity or other known predisposing medical condition
8. Dental crowding and high or narrow palate
9. Arachnodactyly, as defined in one or more of the following: (i) positive wrist sign (Steinberg sign) on both sides; (ii) positive thumb sign (Walker sign) on both sides
10. Arm span-to-height ≥1.05
11. Mitral valve prolapse (MVP) mild or greater based on strict echocardiographic criteria
12. Aortic root dilatation with Z-score > +2

Feature B —positive family history, with one or more first-degree relatives independently meeting the current diagnostic criteria for hEDS.

Feature C —musculoskeletal complications (must have at least 1 of 3 ):

1. Musculoskeletal pain in 2 or more limbs, recurring daily for at least 3 months
2. Chronic, widespread pain for ≥3 months
3. Recurrent joint dislocations or frank joint instability, in the absence of trauma (a or b)
a. Three or more atraumatic dislocations in the same joint or two or more atraumatic dislocations in two different joints occurring at different times
b. Medical confirmation of joint instability at two or more sites not related to trauma

Criteria 3: All these prerequisites must be met: absence of unusual skin fragility, exclusion of other heritable and acquired connective tissue disorders including autoimmune rheumatologic conditions, and exclusion of alternative diagnoses that may also include joint hypermobility due to poor muscle tone (hypotonia) and/or connective tissue laxity.

Other problems (which are not necessarily present) include recurrent joint dislocations, chronic joint/limb pain, and positive family history.

Making the diagnosis can sometimes be complicated by the fact that joint hypermobility is more common in females and young children. Also, joint hypermobility may lessen with age, especially with the development of arthritis or after surgery. In these cases, it would be important to note a past history of joint laxity.

There is a range of conditions which can accompany hEDS, although there is not enough data for them to become part of the diagnostic criteria. While they’re associated with hEDS, they’re not proven to be the result of hEDS and they’re not specific enough to be criteria for diagnosis. Some of these include sleep disturbance, fatigue, postural orthostatic tachycardia, functional gastrointestinal disorders, dysautonomia, anxiety, and depression. These conditions are sometimes more debilitating than the joint symptoms as they often impair daily life, and should be considered and treated.

Although the underlying genetic cause of hypermobile Ehlers-Danlos syndrome is unknown, it appears to follow an autosomal dominant pattern of inheritance. This means that to be affected, a person only needs a change (mutation) in one copy of the responsible gene in each cell. In some cases, an affected person inherits the mutation from an affected parent. Other cases may result from new ( de novo) mutations in the gene. These cases occur in people with no history of the disorder in their family. A person with hypermobile EDS has a 50% chance with each pregnancy of passing along the mutated gene to his or her child.

The long-term outlook (prognosis) for people with hypermobile Ehlers-Danlos syndrome depends on the severity of the condition and the signs and symptoms present. Although this form of EDS does not typically impact life expectancy, musculoskeletal (muscle and bone) pain and joint instability can have a significant impact on daily function and quality of life.

The treatment of hypermobile Ehlers-Danlos syndrome depends on the signs and symptoms present in each person. For example, physical therapy is often recommended to strengthen muscles and improve joint stability. Assistive devices such as braces, wheelchairs, or scooters may be necessary depending on the severity of joint instability. Pain medications may be prescribed to manage severe musculoskeletal (muscle and bone) pain. Affected people may be monitored for the development of osteopenia (low bone density) and aortic root dilatation (enlargement of the blood vessel that distributes blood from the heart to the rest of the body).

GeneReviews (see below) offers more detailed information regarding the treatment and management of hypermobile EDS.

Please speak to your healthcare provider if you have any questions about your personal medical management plan.