HHE Rheumatology and musculoskeletal supplement 2018 | Page 12

Table 1
Types of EDS
Subtype
Inheritance pattern
Genetic basis
Protein involved
Classical EDS( cEDS)
Autosomal dominant
COL5A1, COL5A2
Type V collagen
Classical EDS rare( cEDS)
Autosomal dominant
COL1A1 c. 934C } T,
Type I collagen
p.( Arg312Cys)
Classical-like EDS( clEDS)
Autosomal recessive
TNXB
Tenascin XB
Cardiac-vulvular EDS( cvEDS)
Autosomal recessive
COL1A2( biallelic
Type I collagen
mutations that lead to COL1A2 NMD and absence of pro2( I) collagen chains
Vascular EDS( vEDS)
Autosomal dominant
COL3A1
Type III collagen
Vascular EDS rare( vEDS)
Autosomal dominant
COL1A1
Type I collagen
c. 934C } T, p( Arg312Cys) c. 1720C } T, p.( Arg574Cys) p.( Arg1093Cys)
Hypermobile EDS( hEDS)
Autosomal dominant
Unknown
Unknown
Arthrochalasia EDS( aEDS)
Autosomal dominant
COL1A1, COL1A2
Type I collagen
Dermatosparaxis EDS( dEDS)
Autosomal recessive
ADAMTS2
ADAMTS-2
Kyphoscoliotic EDS( kEDS)
Autosomal recessive
PLOD1
LH1
FKBP14
FKBP22
Brittle cornea syndrome( BCS)
Autosomal recessive
ZNF649
ZNF649
PRDM5
PRDM5
Spondylodysplastic EDS( spEDS)
Autosomal recessive
CHST14
D4ST1
DSE
DSE
Myopathic EDS( mEDS)
Autosomal recessive OR
COL12A1
Type XII collagen
Periodontal EDS( pEDS)
Autosomal dominant
C1R
C1r
www. ehlers-danlos. com
began in the late 1960s. The most widely spread and used criteria – the Ville Franche criteria – were published in 1998, where a simplified classification was proposed creating six major subtypes, for which major and minor clinical criteria were defined, and substituted the previously used Roman numeral types.
In response to the varied needs listed above, new diagnostic criteria and management and care guidelines were published in March 2017 in the American Journal of Medical Genetics. The new criteria classified the EDS into thirteen subtypes. Each EDS subtype has a set of clinical criteria that help define diagnosis; physical signs and symptoms will be matched up to the major and minor criteria to identify the subtype most relevant. For the first time, hypermobility spectrum disorders( HSD) were described.
As well as the more known clinical manifestations of EDS affecting the joints and skin, there can also be chronic, early onset, debilitating musculoskeletal pain, chronic fatigue and other comorbidities in other systems in the body such as gastrointestinal, autonomic and immune system. There is also clinical evidence of a prevalence of neurological and psychological issues in this patient group, but more research is needed in all these areas.
There is substantial symptom overlap between the EDS subtypes and other connective tissue disorders, including HSD. When the gene mutation is known, a definitive diagnosis for all the EDS subtypes also calls for confirmation by genetic testing. The gene is known in all the different EDS forms, apart from hypermobile EDS( hEDS). There is no genetic marker for any of the hypermobility spectrum disorders.
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What are HSD? The issue of those with symptomatic hypermoblility who do not full the criteria of hypermobile EDS needed to be addressed. These people still require validation, treatment and management and we could not move forward with EDS, without considering this part of the population. As a response to this, the HSD were developed.
HSD are a group of clinically relevant conditions related to joint hypermobility( Table 2). HSD are intended to be diagnosed after other possible answers are excluded. HSD, just like hEDS, can have significant effects on health. Whatever the problems that arise, whatever the diagnosis, it is important that these effects are managed appropriately and that each person is
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