Updated Ehlers-Danlos Criteria

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
				c.934C>T, p.(Arg312Cys)
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.934C>T, p.(Arg312Cys)
				c.1720C>T, p.(Arg574Cys)
				c.3227C>T, p.(Arg 1093Cys)
5	Hypermobile EDS	hEDS	AD	Unknown	Unknown
6	Arthrochalasia EDS	aEDS	AD	COL1A1, COL1A2	Type I collagen
7	Dermatosparaxis EDS	dEDS	AR	ADAMTS2	ADAMTS-2
8	Kyphoscoliotic EDS	kEDS	AR	PLOD1	LH1
				FKBP14	FKBP22
9	Brittle Cornea Syndrome	BCS	AR	ZNF469	ZNF469
				PRDM5	PRDM5
10	Spondylodysplastic EDS	spEDS	AR	B4GALT7	β4GalT7
				B3GALT6	β3GalT6
				SLC39A13	ZIP13
11	Musculocontractural EDS	mcEDS	AR	CHST14	D4ST1
				DSE	DSE
12	Myopathic EDS	mEDS	AD or AR	COL12A1	Type XII collagen
13	Periodontal EDS	pEDS	AD	C1R	C1r
				C1S	C1s
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
• MVP
• 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:

1. Absence of unusual skin fragility which should prompt consideration of other types of EDS.
2. Exclusion of other heritable and acquired connective tissue disorder with autoimmune connective tissue disorder (ie Lupus, RA).
3. 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).

 

References

American Journal of Medical Genetics, Part C. (Seminars in Medical Genetics), March 2017.

Filed under: pain management

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