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CUTIS LAXA


CUTIS LAXA
Cutis laxa is an unusual skin disease with multisystem complications. It has highly characteristic cutaneous findings. Laxity of the skin is the hallmark of this disease. The skin becomes easily stretched, and there is little elastic rebound. As patients age, gravity alone can make the skin droop to a disfiguring degree. Some forms of cutis laxa are incompatible with life, and those affected die in infancy. Many variants of cutis laxa have been described. With the discovery of the responsible gene defects, the phenotypes of this disease that are seen clinically have been better defined on the genetic level. Acquired variants of cutis laxa have been described.


CUTIS LAXA

Clinical Findings: Cutis laxa has no sexual or racial predilection. The cutaneous hallmark of the disease is loose, hanging skin with a lack of elasticity. The skin can be pulled with little resistance; the normal return of the skin to its preexisting state is delayed. The skin in the axillae and groin folds is prominently affected, as is the facial skin. The face is said to take on a “hound dog” appearance. All skin is involved to varying degrees, but the effects are most noticeable in areas of the face and in the skin folds. The overlying epidermis is completely normal, and the adnexal structures are spared.
Internal manifestations are variable and are more common with the autosomal recessive forms of the disease. The pulmonary, cardiovascular, and gastrointestinal systems can be affected by fragmentation or loss of elastic tissue, leading, respectively, to emphysema, aneurysms, and diverticula.
Those with the autosomal dominant form appear to have normal life spans, whereas those with the other variants have significantly shortened life spans secondary to severe systemic involvement.

Pathogenesis: Many modes of inheritance have been reported for cutis laxa, including autosomal recessive, autosomal dominant, and X-linked recessive forms. The X-linked form is now considered to be the same disease as Ehlers-Danlos syndrome IX. This form is caused by a defect in a copper-dependent adenosine triphosphatase (ATPase) protein found within the Golgi apparatus.
There are two autosomal recessive variants of cutis laxa. The autosomal recessive variant type I is extremely rare, and those afflicted typically die early in infancy from severe pulmonary and multisystem failure. Auto-somal recessive type I cutis laxa has been found to be caused by a defect in the fibulin-5 gene (FBLN5). The product of this gene is critical in producing functional elastic fibers. Its absence is incompatible with life. Type II autosomal recessive cutis laxa is more commonly encountered than type I. The genetic defect in type II cutis laxa has yet to be defined. Patients with type II experience developmental delay and have varying amounts of joint laxity.
The most frequently seen form of cutis laxa is the autosomal dominant form, which is caused by a defect in the elastin gene (ELN). Many different mutations in this gene have been described, and they lead to slightly different phenotypes of the disease.
All of these gene defects lead to abnormalities in the elastic fiber protein, resulting in elastolysis. Various defects lead to different irregularities in the elastic fibers, but the end result in all forms is seen clinically as cutis laxa.

Histology: Histological examination of skin biopsies from patients with cutis laxa reveals varying degrees of elastic fiber damage and/or loss. The best way to appreciate this is with special staining to highlight elastic tissue. In some cases, there is a complete loss of elastic fibers; in others, fragmented and reduced amounts of elastic tissue are seen.
Treatment: The main goals of therapy is to screen for underlying cardiac or gastrointestinal abnormalities and for the possibility of aortic aneurysm or gastrointestinal diverticula formation. There is no medication that can reverse the genetic defect, and no gene replacement therapy is available. Excessive skin can be surgically removed to improve functionality and cosmesis.

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