In May 2017, there were several changes in the criteria for the diagnosis of what used to be Ehlers-Danlos Syndrome Type III, hypermobility type. First, the name has been changed to hypermobile Ehler-Danlos Syndrome or hEDS. Instead of six types, there are now 13 types.
|Clinical EDS subtype||Abbreviation||IP||Genetic Basis||Protein|
|1||Classical EDS||cEDS||AD||Major: COL5A1, COL5A1||Type V collagen|
|Rare: COL1A1||Type I collagen|
|2||Classical-like EDS||clEDS||AR||TNXB||Tenascin XB|
|3||Cardiac-valvular||cvEDS||AR||COL1A2 (bilallelic mutations that lead to COL1A2||Type I collagen|
|NMD and absence of pro α2(I) collagen chains)|
|4||Vascular EDS||vEDS||AD||Major: COL3A1||Type III collagen|
|Rare: COL1A1||Type I collagen|
|c.3227C>T, p.(Arg 1093Cys)|
|6||Arthrochalasia EDS||aEDS||AD||COL1A1, COL1A2||Type I collagen|
|9||Brittle Cornea Syndrome||BCS||AR||ZNF469||ZNF469|
|12||Myopathic EDS||mEDS||AD or AR||COL12A1||Type XII collagen|
|IP, inheritance pattern; AD, autosomal dominant; AR, autosomal recessive; NMD, nonsence-mediated mRNA decay|
hEDS continues to have no obvious known genetic testing and is only diagnosed through clinical testing.
As mentioned earlier, the Beighton scale is used to determine if a person is hypermobile. This continues to be an important determinant for hypermobility. A 5/9 score in adults is needed in order to meet this requisite. However, because age has an effect on flexibility (ie with age, you tend to become stiffer), there is a Five Point Questionnaire that determines if there is a history of hypermobility. The five points are the following:
- 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 a split?
- As a child or teenager, did your shoulder or kneecap dislocate on more than one occasion?
- Did you consider yourself “double-jointed”?
If you answer yes to two or more questions, then you have met the criteria for hypermobility (with 80-85% sensitivity and 80-90% specificity).
The Beighton Scale and Five Point Questionnaire are the first part of three criteria that need to be met in order to qualify for the diagnosis of hEDS. This criterion also meets the diagnosis of hypermobility (you can have generalized joint hypermobility without a diagnosis of hEDS).
The second criterion has three parts (A, B, and C), of which two must be met to qualify. Part A is a series of 12 symptoms, of which five must be met in order to quality:
- Unusually velvety skin
- Mild skin hyperextensibility
- Unexplained striae on back, groins, thighs, breast or abdomen in adolescents, men or prepubeteral women without a history of significant gain/loss or weight.
- Bilateral piezogenic papules of the heel
- Recurrent or multiple abdominal hernias (umbilical, inguinal, crural)
- Atrophic scarring with papyraceous or meosideric scars
- Pelvic floor, rectal and/or uterine prolapse in children, men or nulliparous women without a history of morbid obesity or other known predisposing medical conditions.
- Dental crowding or high or narrow palate
- Arachnodactyly (fingers & toes, long and slender), Steinberg Sign (thumb beyond palm), Walker-Murdoch sign (thumb overlapping fifth finger around wrist)
- Arm span to height ≥ 1.05
- Aortic root dilation
Part B is a positive family history of one or more first degree relatives, independently meeting the criteria of hEDS.
Part C is musculoskeletal complaints; a patient must have at least one to qualify:
- Daily musculoskeletal pain at least three months in two or more limbs
- Chronic widespread pain for more than 3 months.
- Recurrent joint dislocation or frank instability in the absence of trauma (A or B)
- 3 or more atraumatic joint dislocations in the same joint or two or more atraumatic dislocations in two different joints occurring at two different times.
- Medical confirmation of joint (2 or more) instability
The third criterion contains three pre-requisites, all of which 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 disorder with autoimmune connective tissue disorder (ie Lupus, RA).
- Exclusion of alternative diagnoses that may also include joint hypermobility by means of hypotonia and/or CT laxity. Alternative diagnoses and diagnostic categories include, but not limited to, neuromuscular diseases, myopathic EDS, Bethlem myopathy, or HCTD (ie other types of EDS), Loeys-Dietz Syndrome (Marfan), and skeletal dysplasias (ie OI).
American Journal of Medical Genetics, Part C. (Seminars in Medical Genetics), March 2017.