Inherited connective tissue disorders are clinically and genetically diverse conditions affecting the skin, joints, and a variety of extracutaneous tissues, including the cardiovascular (CV) system. The nature and severity of the skin phenotype is dependent on the type of mutation as well as the role of the affected protein on dermal structure and function (see Chapter 63). The diagnosis of many inherited connective tissue disorders is clinical, although CLIA-approved genetic testing is increasingly available. A listing of research laboratories that may offer testing can be found at http://www.genetests.org.
Ehlers–Danlos Syndromes at a Glance
- Combined incidence of almost 1 in 5,000 persons.
- Seven subtypes.
- Most commonly autosomal dominant (classical and hypermobile types).
- The gene encoding collagen V is most often affected.
- Cutaneous features include soft, velvety skin that bruises easily and wounds that heal as thin, atrophic, gaping scars.
- Extracutaneous manifestations include hypermobile joints with frequent dislocations, problems with pregnancy and delivery, and, less commonly, cardiovascular manifestations, particularly aortic root dilatation.
- Information for patients and professionals at http://www.ehlers-danlos.org and http://www.ednf.org.
A variety of genetically and clinically heterogeneous inherited conditions characterized by varying degrees of skin fragility and hyperextensibility, joint hypermobility, and easy bruising, have been collected under the rubric of the Ehlers–Danlos syndromes (EDS). A new classification system was proposed in 19971 to consolidate and simplify existing subgroups (Table 137-1). Despite these revisions, many patients defy clear-cut classification due to overlapping features. The spectrum of EDS disease severity ranges from nearly imperceptible findings to severe, debilitating disease. As such, it is difficult to estimate EDS prevalence, but if milder forms are included it may be as high as 1:5,000 individuals. The kyphoscoliosis, arthrochalasia, and dermatosparaxis types are considerably less common than the classical, hypermobility, and vascular types. Confusion over the diagnosis of the hypermobility type and its overlap with joint hypermobility syndrome interferes with prevalence estimates. If inclusive definitions are used, it may be the most common subtype. Generalized joint hypermobility is the consistent and unifying finding in all forms of EDS.3 EDS types other than the common classic type and the life-threatening vascular type are discussed in the online edition of the book.
Table 137-1 The Ehlers–Danlos Syndromes: Clinical Subtypes and Associated Defects ||Download (.pdf)
Table 137-1 The Ehlers–Danlos Syndromes: Clinical Subtypes and Associated Defects
Classical/(130000 and 130010)
Hyperextensible skin; easy bruising; wide, atrophic scars; hypermobile joints
Collagen type V/(COL5A1, COL5A2)
Smooth, velvety skin; joint hypermobility
Unclear for most; collagen type III; tenascin XB/(COL3A1; TNXB)a
Thin, translucent skin with easy bruising; arterial and visceral rupture; typical facies
Collagen type III/(COL3A1)
Kyphoscoliosis/(225400 and 229200)
Atrophic scars, easy bruising; neonatal hypotonia; scoliosis; ocular rupture; marfanoid habitus
Hyperextensible and fragile skin; severe joint hypermobility; congenital hip dislocation