• Clinically and genetically heterogeneous group of connective tissue disorders caused by defective function of various collagens, collagen-processing enzymes, and associated proteins.

• The cardinal physical findings of hyperextensible, fragile skin, and hypermobile joints (Fig. 80.1) are present to varying degrees in different subtypes of EDS (Table 80.1).

• Manifestations of cutaneous fragility include easy bruising (sometimes leading to suspicion of a bleeding disorder; see Fig. 80.1D) and gaping, ‘fish-mouth’ wounds from minor trauma that heal with widened, atrophic scars (see Fig. 80.1C); additional findings may include smooth velvety skin, molluscoid pseudotumors (fleshy nodules in sites of repetitive trauma), subcutaneous spheroids over bony prominences (small, hard nodules that represent calcified fat lobules), piezogenic papules (see Chapter 82), and elastosis perforans serpiginosa (see Chapter 79).

• Rx: prevention of trauma; patients with the vascular type of EDS require close monitoring (especially during pregnancy) to avoid serious complications.

• Uncommon autosomal recessive disorder characterized by distorted and calcified elastic fibers in the skin, eyes, and cardiovascular system; caused by mutations in the ABCC6 gene, which encodes an ABC-cassette transporter (expressed primarily in the liver) that exports anti-mineralization factors into the circulation.

• Skin changes and asymptomatic ocular findings usually appear during the first two decades of life, with ocular and cardiovascular complications typically developing in the third and fourth decades.

• Thin yellowish papules coalesce to form cobblestoned plaques (resembling ‘plucked chicken skin’) on the lateral neck and in other flexural sites (e.g. antecubital and popliteal fossae, axillae, groin) (Fig. 80.2); decreased elasticity leads to sagging skin in affected areas (see Fig. 80.2D), and yellow papules on the oral mucosa may be evident (see Fig. 80.2E).

• Early ocular findings include angioid streaks, which reflect breaks in the calcified elastic lamina of Bruch’s membrane (also seen in other metabolic/genetic disorders, e.g. sickle cell anemia), and mottling of the retinal pigment epithelium; choroidal neovascularization and hemorrhage can result in progressive loss of vision.

• Calcification of elastic fibers in the walls of medium-sized arteries leads to luminal narrowing and clinical sequelae such as intermittent claudication, renovascular hypertension, angina, myocardial infarction, and stroke; GI hemorrhage may also occur.

• DDx: PXE-like cutaneous and extracutaneous findings can be seen in generalized arterial calcification of infancy (ENPP1 mutations), PXE-like disorder with coagulation factor deficiency (GGCX mutations), β-thalassemia, and sickle cell anemia; other conditions featuring PXE-like skin lesions are outlined in Table 80.2.

• Rx: an approach to management of PXE is presented in Table 80.3.

• Heterogeneous group of heritable and acquired disorders (Table 80.4) characterized by loose, sagging skin due to sparse and fragmented elastic fibers.

• Skin involvement is often generalized, giving patients a prematurely aged appearance (Fig. 80.3), but it may be localized to acral or periorbital sites; cutaneous findings are present at birth in most heritable forms of cutis laxa, developing later in acquired cutis laxa and some autosomal dominant variants.

• Extracutaneous manifestations can include emphysema, hernias (e.g. umbilical, inguinal), diverticula (e.g. GI, genitourinary), cardiovascular defects, musculoskeletal or craniofacial anomalies, and developmental delay; these findings are most common in autosomal recessive variants and occasionally occur in acquired forms.

• DDx: PXE and related conditions, mid-dermal elastolysis (see Chapter 82), anetoderma (see Chapter 82; smaller, circumscribed lesions), hereditary gelsolin amyloidosis.

• Rx: reconstructive surgery for cutaneous disease; multidisciplinary approach for internal involvement.

• Additional heritable connective tissue disorders with cutaneous manifestations are summarized in Table 80.5.