EDS and hEDS
The Ehlers-Danlos syndromes (EDS) are named after two doctors, Dr. Edvard Lauritz Ehlers and Dr. Henri-Alexandre Danlos, who described the condition in the early twentieth century.
The Ehlers-Danlos syndromes (EDS) are a group of 14 heritable connective tissue disorders that are caused by genetic changes except hEDS whose gene has yet to be identified.
They are heterogenous and each type of EDS has its own set of features with distinct diagnostic criteria. Some features are seen across all types of EDS, including joint hypermobility, skin hyperextensibility, and tissue fragility.
Most forms resolved from mutation in the genes encoding collagen or enzymes that process collagen or other connective tissue elements.
What is joint hypermobility?
Joint hypermobility means that a person’s joints have a greater range of motion than is expected or usual. Some people have joint hypermobility that does not cause them pain or other issues. However, some people with joint hypermobility also have joint instability. Joint instability occurs when the bones of a joint aren’t held in place securely. This can lead to joint subluxations, dislocations, sprains, and other injuries. Joint instability can cause both acute and chronic pain and interfere with daily life.
Joint hypermobility is observed throughout the body in most types of EDS, but hypermobility may be limited to the hands and feet in some types. Although joint hypermobility is observed across all types of EDS, not everyone with a type of EDS has joint hypermobility.
THE BEIGHTON SCORING SYSTEM
The Beighton Scoring System measures joint hypermobility on a 9-point scale. The joints assessed are: Use a goniometer if needed.
Knuckle of both little/fifth/pinky fingers
Base of both thumbs
Elbows
Knees
Spine
With the palm of the hand and forearm resting on a flat surface with the elbow flexed at 90°, if the metacarpal-phalangeal joint of the fifth finger can be hyperextended more than 90° with respect to the dorsum of the hand, it is considered positive, scoring 1 point.
With arms outstretched forward but hand pronated, if the thumb can be passively moved to touch the ipsilateral forearm it is considered positive scoring 1 point.
With the arms outstretched to the side and hand supine, if the elbow extends more than 10°, it is considered positive scoring 1 point.
While standing, with knees locked in genu recurvatum, if the knee extends more than 10°, it is considered positive scoring 1 point.
With knees locked straight and feet together, if the patient can bend forward to place the total palm of both hands flat on the floor just in front of the feet, it is considered positive scoring 1 point.
The 5-part questionnaire for hypermobility
Can you now [or could you ever] place your hands flat on the floor without bending your knees?
Can you now [or could you ever] bend your thumb to touch your forearm?
As a child, did you amuse your friends by contorting your body into strange shapes or could you do the splits?
As a child or teenager, did your kneecap or shoulder dislocate on more than one occasion?
Do you consider yourself “double-jointed”?
Answering yes to 2 or more of these questions suggests hypermobility (sense 85%, spec 90%).
The 5-part questionnaire was designed as a quick check to see if someone has or may have had hypermobility (Hakim and Grahame, 2003). It has been used in clinics and in research and has been translated for use in several languages and tested in several countries (Glans et al., 2020). It was tested and designed as an alternative to the Beighton score. If you answer ‘yes’ to two or more of the questions, it strongly predicts a Beighton score of 4 or more, 4 being the cut-off point in criteria at the time the questionnaire was published.
Example:
Ehler-Danlos Screening:
1. Can you now (or could you ever) placing her hands flat on the floor without bending her knees? Yes
2. Can you now (or could you ever bend your thumb to touch your forearm? Yes
3. As a could you do the splits? Yes
4. As a child or teenager did your shoulder or kneecap dislocate on more than one occasion? Yes
5. Do you consider your cell double-jointed? Yes.
Beighton score: 9/9.
1. With the palm of the hand and forearm resting on a flat surface with the elbow flexed at 90°, the metacarpal-phalangeal joint of the fifth finger can be hyperextended more than 90° with respect to the dorsum of the hand, bilaterally: 2 points.
2. With arms outstretched forward but hand pronated, the thumb can be passively moved to touch the ipsilateral forearm, bilaterally: 2 points.
3. With the arms outstretched to the side and hand supine, the elbow extends more than 10°, bilaterally: 2 points.
4. While standing, with knees locked in genu recurvatum, the knee extends more than 10°, bilaterally: 2 points.
5. With knees locked straight and feet together, she can bend forward to place the total palm of both hands flat on the floor just in front of her feet: 1 point.
Hypermobility spectrum Disorder
Hypermobility spectrum disorders (HSD) are connective tissue disorders that cause joint hypermobility, instability, injury, and pain. Other problems such as fatigue, headaches, GI problems, and autonomic dysfunction are often seen as part of HSD.
What is hypermobility?
Joint hypermobility means that a person’s joints have a greater range of motion than is expected or normal.
Most babies and children are naturally very flexible. Many people become less flexible as they grow, but hypermobility continues into adulthood for some, up to about 20% of people. Being “flexible,” “bendy,” or “double-jointed” is not usually a problem, and for some, like dancers or gymnasts, it is an advantage. Hypermobility that does not cause pain or other symptoms is referred to as “asymptomatic joint hypermobility” and does not need to be treated.
The problem occurs when joints are not just hypermobile but are also unstable. Joint instability occurs when the bones of a joint aren’t held in place securely. This can lead to joint subluxations, dislocations, sprains, and other injuries. Joint instability can cause both acute and chronic pain and interfere with daily life.
Joint hypermobility and/or instability may be a person’s only problem. It can also occur as part of a known syndrome, such as types of Ehlers-Danlos syndromes (EDS), Marfan syndrome, or Down syndrome. The hypermobility spectrum disorders occur when a person has symptomatic joint hypermobility that cannot be explained by other conditions. A person with HSD may have joint instability as their only concern or may have other medical issues as well.
What is a disorder?
A medical disorder is defined as an illness or condition that disrupts normal physical or mental functions. If joint hypermobility causes problems that disrupt normal function, it is a disorder. If joint hypermobility isn’t causing any issues or pain, it is not considered to be a disorder.
What is a spectrum disorder?
A spectrum disorder refers to a condition that has wide variation in both the type and severity of symptoms people experience. For example, people with HSD may have mild or severe joint involvement. They may also experience one, two, or many other symptoms such as fatigue, dizziness, constipation, or headaches, and any of these problems may be mild or severe.
Two different people with HSD may experience very different symptoms. For example, one person with HSD may have severe joint instability, fatigue, and autonomic dysfunction. Another person with HSD may have mild joint instability but severe headaches and gastrointestinal issues. Both people experience HSD differently, but neither person has “more HSD” than the other.
What are the types of HSD?
Four types of HSD are described, based on the type of joint hypermobility present.
Generalized HSD (G-HSD): HSD in which joint hypermobility occurs throughout the body. Positive Beighton Score
Peripheral HSD (P-HSD): HSD in which joint hypermobility is limited to the hands and feet. Negative Beighton Score.
Localized HSD (L-HSD): HSD in which joint hypermobility occurs in a single joint or group of joints in the same area. Negative Beighton Score. Joint hypermobility limited to a single joints or body parts.
Historical HSD (H-HSD): HSD in which there is history of generalized joint hypermobility, but without current evidence of generalized joint hypermobility on exam. Negiative BS;
Prevalence
A condition is considered rare if it affects less than 1 in 2000 people. Figures may be presented in different ways, but they mean the same thing. For example, a document might say that 5 per 10,000 people, or less than 50 per 100,000 is rare.
The combined prevalence of HSD and hEDS is in the order of 1 in 600 to 1 in 900. Expert opinion is that HSD is common and that hEDS is likely to be common. However, at this time it is not possible to say what the prevalence figure is for each of HSD and hEDS separately because this has not been studied yet.
Expert opinion is that HSD is common. The prevalence of hEDS is now thought to be greater than previously described, but by how much is not yet clear. Healthcare professionals and organizations that are not aware that they are likely to see people with HSD or hEDS risk missing the diagnoses, not knowing how to care for people with these conditions, and not having the resources to care for them. For too many in our community, this is not an imaginary state; it is a lived experience.
HSD and hEDS: 1900 per million population.
hEDS: 320 per million population.
cEDS (classic EDS): 50 per million population.
vEDS (vascular EDS): 10 per million population.
the International Consortium on the Ehlers–Danlos Syndromes proposes 6 for pre-pubertal children and adolescents, 5 for pubertal men and women up to the age of 50, and 4 for those >50 years of age for hEDS
Diagnosis of hEDS:
The cause(s) of hEDS have not been identified, so there is currently no laboratory test available to diagnose hEDS. The diagnosis of hEDS is given to those who meet the clinical diagnostic criteria for hEDS.
To meet the diagnostic criteria for hEDS, a person must meet all three criteria (1 and 2 and 3).
Criterion 1: Generalized joint hypermobility.
Criterion 2: Two or more of the following features (A, B, and C) must be present: Either A or B or A or C or B or C...
Feature A: Manifestations of a connective tissue disorder (must have five or more of the following):
Unusually soft or velvety skin
Mild skin hyperextensibility
Unexplained striae such as striae distensae or rubrae at the back, groins, thighs, breasts, and/or abdomen in adolescents, men, or pre-pubertal women without a history of significant gain or loss of body fat or weight
Bilateral piezogenic papules of the heel
Recurrent or multiple abdominal hernia(s) (e.g., umbilical, inguinal, crural)
Atrophic scarring involving at least two (2) sites and without the formation of truly papyraceous and/or hemosideric scars as seen in classical EDS
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
Dental crowding and high or narrow palate
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 sidesArm span-to-height ratio ≥ 1.05
Mitral valve prolapse (MVP) mild or greater based on strict echocardiographic criteria
Aortic root dilatation with Z-score >+2
Feature B: Positive family history (one or more first-degree relatives independently meet the current diagnostic criteria for hEDS)
Feature C: Musculoskeletal complications (must have at least one of the following)
Musculoskeletal pain in two or more limbs, recurring daily for at least three (3) months
Chronic, widespread pain for at least three (3) months
Recurrent joint dislocations or frank joint instability, in the absence of trauma (a or b)
(a) Three (3) or more atraumatic dislocations in the same joint or two (2) or more atraumatic dislocations in two (2) different joints occurring at different times
OR
(b) Medical confirmation of joint instability at two (2) or more sites not related to trauma
Criterion 3: ALL of the following prerequisites must be met:
Absence of unusual skin fragility, which should prompt consideration of other types of EDS
Exclusion of other heritable and acquired connective tissue disorders, including autoimmune rheumatologic conditions
In patients with an acquired connective tissue disorder (e.g., lupus, rheumatoid arthritis, etc.), additional diagnosis of hEDS requires meeting both Features A and B of Criterion 2. Feature C of Criterion 2 (chronic pain and/or instability) cannot be counted towards a diagnosis of hEDS in this situation.
3. Exclusion of alternative diagnoses that may also include joint hypermobility by means of hypotonia and/or connective tissue laxity. Alternative diagnoses and diagnostic categories include, but are not limited to:
Neuromuscular disorders (such as myopathic EDS and Bethlem myopathy)
Other heritable connective tissue disorders (such as other types of EDS, Loeys–Dietz syndrome, Marfan syndrome)
Skeletal dysplasias (such as osteogenesis imperfecta)
Domains:
1. Pain
2. Fatigue
3. Neuromusculoskeletal
4. Cardiac dysautonomia,
5. Gastrointestinal
6. Urogenital
7. Anxiety
8. Depression
Management advice for hEDS:
Education, advice, and nondrug treatment should be offered first of all patients, and include education on avoiding or reducing exposure to triggering factors, withdrawing medications that might worsen symptoms, maintaining good water intake and salt balance, raising legs when resting, compression garments, increasing exercise (adapted to achieve hEDS needs). When prescribing exercise, the program might be adapted: Aerobic activities with a local resistive component, dynamic exercise (involving joint movement), exercise lying down, exercising and water (depending on temperature). Training at a target heart rate of 75% of estimated maximum heart rate for about 30 minutes per session, 2-3 times per week as advised, adapted according to level of disability. Increase of fluid intake, with added sodium, and the use of medical compression stockings during and after exercise can be helpful. Meals should be avoided 1 hour prior to an exercise session. To prevent a sudden drop in blood pressure after training, a person should cool down with gentle movements. In those with more significant impairment of daily function, and poor response known drug treatments, medication that may help include: Fludrocortisone, midodrine, beta-blockers, ivabradine, methylphenidate/dextro amphetamine, hormonal contraceptives, desmopressin, pyridostigmine, clonidine, dihydroxy phenol searing, and octreotide. Saline infused into the vein over 1 to 2 hours may help in extreme cases, but carries risks.
One underlying assumption was that most, if not all, of these types of EDS were a consequence of alterations in fibrillar collagen genes or in genes that encoded collagen modifiers.
Brittle cornea syndrome
https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-8-68
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3659006/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698176/
https://eyewiki.aao.org/Brittle_Cornea_Syndrome
https://www.preventiongenetics.com/testInfo?val=Brittle-Cornea-Syndrome-Panel
https://www.invitae.com/us/providers/test-catalog/test-434340
Skin signs in Ehlers–Danlos syndrome: clinical tests and para-clinical methods
L Remvig,PH Duhn,S Ullman,J Arokoski,J Jurvelin,A Safi, show all
Pages 511-517 | Accepted 16 Mar 2010, Published online: 05 Aug 2010
No history of mitral valve prolapse, dural ectasia, myopia, ectopia lentis, retinal detachment, dental crowding, bifid or wide uvula, high palate, pectus deformity, pneumothorax, scoliosis, club feet, multiple fractures, osteoarthritis, hypermobility, joint dislocations, hernias, striae, soft or hyperextensible or thin skin, abnormal scarring, varicose veins, easy bruising, pes planus, severe allergies, inflammatory GI disease, tendon or muscle rupture, congenital hip dysplasia, or organ rupture.
Reactive hypoglycemia is not a feature of EDS although some EDS patient have reported it but no different than the rest of the population. Reactive hypoglycemia (RH) is the condition of postprandially hypoglycemia occurring 2-5 hours after food intake. RH is clinically seen in three different forms as follows: idiopathic RH (at 180 min), alimentary (within 120 min), and late RH (at 240–300 min).
Emergency Action Plan:
https://thevedsmovement.org/wp-content/uploads/2020/08/VEDS-MOVEMENT.pdf
https://www.chronicpainpartners.com/basic-emergency-care-planning-for-eds-patients/
https://www.chronicpainpartners.com/dysautonomia-patient-guide/
https://www.chronicpainpartners.com/mastering-appointments-successfully-with-eds/