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.
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.
