This syndrome continues to be a challenge to practicing dermatologists. The wide spectrum of phenotypic manifestations blend at one end to the constitutive features in the general population and at the other end can be a cause of early demise. The molecular basis of all six major forms of EDS has now been deciphered, the mutations residing either in the genes encoding collagens, enzymes modifying the primary collagen translation products, or tenascin-X, another connective tissue protein.

The major type of EDS not to be missed is the vascular type (old EDS IV). They are at high risk for arterial and intestinal ruptures, and often unexpectedly, to uterine rupture during labor, with catastrophic consequences. As soon as you establish this diagnosis, get a cardiovascular evaluation, paying attention to the aortic root and possible aneurysms.

Another type not to miss is the kyphoscoliosis type (old EDS VI). In some cases one may be able to overcome the enzyme deficiency simply by supplementary ascorbic acid in the diet. In fact, some physicians advocate ascorbic acid for all EDS types.

The previous EDS IX has been excluded from EDS category and is known as the occipital horn syndrome (because of the characteristic bone protrusions at the base of the skull). It is allelic with Menkes syndrome.

General treatment of EDS is protection from trauma, use of shin guards when playing sports, avoid sharp edges of furniture at home. Loose jointedness, particularly affecting knees and hips, can result in early osteoarthrosis; a pediatric orthopedic consultation may be helpful. Mitral valve prolapse is exceedingly common among patients with EDS. JU

This systemic connective tissue disorder is caused by mutations in the fibrillin-1 gene. The phenotypic variability reflects the types of mutations and their consequences at the mRNA and protein levels. The major complications relate to cardiovascular findings, including aortic dilatation, dissection and aneurysms. The patients should be followed closely by cardiovascular surgeons. Lowering blood pressure and using beta-blockers is clearly helpful. The eye problems require regular follow-up by an ophthalmologist. JU

The underlying pathology relates to perturbation in the elastic fiber network, and mutations have been demonstrated both in the elastin and fibulin-5 genes. The clinical spectrum spans from relatively mild skin involvement to extremely severe with skin problem associated with extracutaneous manifestations, including pulmonary emphysema, arterial aneurysms, and vesico-urinary diverticula. Therefore, careful systemic evaluation, especially in patients with congenital forms of cutis laxa, is in order. The inheritance can be either autosomal dominant or autosomal recessive. Acquired, late-onset cutis laxa is often associated with urticarial and/or inflammatory lesions and is sometimes a sequela of acute drug reaction, such as to penicillin. In the latter case, inflammatory cells that contain powerful elastases degrade elastin in the skin, resulting in paucity of elastic fibers. As a result, the entire skin shows progressive sagging, and because of relatively poor repair capacity, new elastic fibers are not formed in adult skin and the sagging is permanent. Solar elastosis tends to aggravate this condition, and sunscreen application should be stressed. Facelifts do provide improvement, but this may be only temporary. JU

This clinical entity can occasionally be a diagnostic problem, particularly because of delayed onset and considerable intrafamilial and interfamilial heterogeneity. Diagnosis can usually be confirmed by skin pathology, but recent identification of the mutated gene, ABCC6, provides a molecular tool to confirm the diagnosis. In cases without definitive cutaneous findings, but with angioid streaks and family history of pseudoxanthoma elasticum (PXE), mutation analysis can be used for presymptomatic diagnosis.

Patients need to be followed by ophthalmologists who may consider laser treatment of retinal hemorrhages. Avoidance of head trauma is important to prevent retinal bleeding. Although total blindness is extremely rare, some patients may become legally blind at a relatively early age. Plastic surgery may be helpful in improving the cosmetic appearance of skin. The major life-threatening problems are myocardial infarct and occasionally, massive gastrointestinal hemorrhages, particularly in families with predominant cardiovascular manifestations. Strongly advise patients against smoking, because it exacerbates intermittent claudication and other cardiovascular problems. Calcium intake is a controversial subject, as it has been suggested that high calcium intake during the childhood or early adolescence results in more severe phenotype. I do not recommend low-calcium diet for adults as it may accelerate development of osteoporosis, and balanced diet including modest amounts of dairy products should be fine for children as well.

Direct patients to the website of PXE International, a patient advocacy organization: www.pxe.org. JU

Different mutations in type I collagen gene are responsible for varying severity of disease … Milder forms are often misdiagnosed as child abuse … However, osteogenesis imperfecta (OI) kids have thinner bones and fracture straight through, abused kids get spiral fractures … Blue sclerae should be looked for when evaluating for abuse … Can diagnose in utero with ultrasound … Looks like severe chondrodystrophies except you often see fractures … May need dentures as children … If teeth involved you usually have worse fractures … One of many dominant syndromes where you get an association with increased paternal age and a new mutation … Confirmation of prenatal and clinical diagnosis is available by collagen examination in cultured fibroblasts and by mutation screening. KH, JW