English Version
T. Wiesmann

Ehlers-Danlos syndrome

Ehlers-Danlos syndrome

Schlüsselwörter Ehlers-Danlos syndrome; ICD 10: Q79.6; inherited connective tissue diseases
Keywords Ehlers-Danlos syndrome; ICD 10: Q79.6; inherited connective tissue diseases
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Ehlers-Danlos syndrome comprises a group of clinically and genetically heterogeneous, [22]. Different defects in the synthesis of collagen lead to an increased elasticity within different types of connective tissue (skin, joints, muscles, tendons, blood vessels and visceral organs). Depending on the specific subtype and individual aspects, defects are mild to life-threatening. The incidence of EDS is estimated as 1:5000, in which the hypermobility-type has the highest prevalence affecting 1 in every 10.000 to 15.000 individuals [20]. It affects men and women of every race and ethni­city but is known to be more common among non-white populations and women [31].

The Villefranche classification from 1998 recognizes six major genetic subtypes: classic (type I and II according to the old “Berlin classification” from 1988), hypermobility (type III), vascu­lar (type IV), kyphoscoliotic (type VI A), arthrochalasis (type VII A&B) and dermatosparaxis (type VII C), most of which are linked to mutations in one of the genes encoding fibrillar collagen proteins or enzymes involved in post-translational modification of these proteins.

Over the last decades, a whole spectrum of novel EDS subtypes and mutations have been identified via next-generation sequencing in an array of new genes. Therefore, in 2017 an international EDS consortium proposed a revised EDS classification, which recognizes 13 cli­nical subtypes: classical EDS (cEDS), classical-like EDS (clEDS), cardiac-valvular (cvEDS), vascular EDS (vEDS), hypermobile EDS (hEDS), arthrochalasia EDS (aEDS), dermato­sparaxis EDS (dEDS), kyphoscoliotic EDS (kEDS), brittle cornea syndrome (BCS), spondylo­dysplastic EDS (spEDS), musculocontractural EDS (mcEDS), myopathic EDS (mEDS) and periodontal EDS (pEDS).

Since many previous literature still refer to the older Villefranche classification [17,31]. For each subtype, a set of clinical major and minor criteria are proposed and are suggestive for diagnosis [17]. However, individual symptoms and severity need to be investigated for each specific patient.

Major criteria for the classic type include severe skin hyperextensibility, atrophic scarring and generalized joint hypermobility (GJH), whereas the classical-like type presents with easy bruisable skin, spontaneous ecchymoses and also skin hyperextensibility (in the absence of atrophic scarring) and GJH with or without recurrent dislocations [17]. GJH in hypermobility-type may be diagnosed via Beighton score, whereby recurrent joint dislocations, mild skin hyperextensibility, striae and chronic pain are further exemplary diagnostic criteria in this type. Probably the most severe type is the vascular subtype with extreme fragile blood vessels and internal organs. Major criteria include arterial rupture at a young age, spontaneous sigmoid colon perforation, uterine rupture (during third trimester in absence of C-section) and carotid-cavernous sinus fistula [17]. Beside skin and joint pathologies, the cardiac-valve type presents with severe progressive cardiac-valvular problems, especially in aortic and mitral valve. The arthrochalasia type may present with congenital bilateral hip dislocation, whereas short limbs, hand and feet occurs in dermatosparaxis EDS. Muscle hypotonia may be present in myotonic, kyphoscoliotic and spondylodysplastic EDS. Muscu­locontractural EDS is among other things characterized by congenital multiple contractures and different cutaneous pathologies. Major criteria of periodontal EDS include severe and intractable periodontitis of early onset (childhood or adolescence) and a lack of attached gingiva [17]. Nevertheless, specific symptoms must be given respect for each individual patient due to overlapping phenomena. In addition to these selected clinical signs, we refer to the new classification mentioned above for detailed major and minor clinical criteria [17].

When compared with the other subtypes of EDS, the vascular type has largely been recognized as having the worst prognosis due to vessel/organ rupture and is associated with early mortality [9]. It accounts for less than 4% of all EDS [21].

On an operational perspective, surgical and anaesthetic pitfalls relate to a mixture of common features shared by most subtypes and complications related to specific variants. Therefore, an accurate patients’ classification should be planned before any invasive proce­dure. Subtypes are caused by autosomal-dominant or autosomal-recessive mechanisms. Approximately 50% of all patients have de-novo mutations with negative family history.


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