Content area
Full Text
Ehlers-Danlos syndrome (EDS) is a heterogeneous group of inherited connective tissue disorders. These are separate and specific conditions that are distinct in features and, where it is known, genetic basis. The skin, joints, blood vessels and internal organs are variably affected (Table 1).
Presentation
With various organ systems potentially affected, the initial presentation can be to one or more medical specialties ( Table 2 ).
Classification
The 1997 Villefranche classification of EDS was based on the identification of genetic alterations affecting the synthesis and structure of type I, III and V collagen.1 Since then, the molec ular genetic basis of other types of EDS has been delineated and a further classification is due. Aside from genetic alterations in collagen, genetic defects affecting the biosynthesis of other components of the extracellular matrix, as well as signalling pathways and intracellular trafficking, can contribute to EDS pathogenesis.2
The Villefranche nomenclature with six subtypes is still widely used. Of these, the classical, vascular and hypermobility types are most commonly seen and are discussed in this review. The arthrochalasic, dermatosparactic and kyphoscoliotic types are rare. Modern molecular techniques have identified specific genes relating to most of the Villefranche subtypes ( Table 3 ).
Classical Ehlers-Danlos syndrome
The triad of joint hypermobility, marked skin hyperextensi-bility ( Fig la ) and widened atrophic scars ( Fig lb ) is the hallmark of this condition. Further cutaneous signs include easy bruising with staining from haemosiderin deposition, subcutaneous spheroids (subcutaneous fat lobules that have lost blood supply and calcified), molluscoid pseudotumours (thickened fleshy lesions particularly over elbows and knees associated with scars ) and the absence of stretch marks ( striae ).
Electron microscopy of the skin shows typic al 'collagen flowers' or 'cauliflowers' ( Fig 2 ), which result from abnormal fibrillogenesis of the collagen fibrils comprising type I and V collagen. Mutations in type V collagen are known to cause classical EDS.3 Many different mutations in type V collagen have been identified. However, there is as yet no obvious genotype-phenotype correlation. Classical EDS is a dominantly inherited condition, although the severity can vary significantly within the same family. A clinical cameo is presented in Box 1.
Cardiology assessment, including echocardiography, is recommended for classical EDS specifically assessing for aortic root dilatation...