Cutis Laxa

Cutis laxa (CL) is a disorder, either acquired or inherited, in which patients have wrinkled, abundant, sagging skin with abnormal elasticity, caused by abnormal structure or function of elastin or other extracellular matrix components. Skin symptoms may be associated with variable systemic involvement, especially in the dominant and in the ARCL1 forms. In the current overview, we focus on genetic forms of CL. The inherited form has a wide genetic variability, including X-linked, autosomal dominant, and autosomal recessive patterns of inheritance. Intriguingly, several of the CL syndromes are inborn errors of metabolism. The most well-known example is Menkes disease, the first metabolic disease reported with old looking, wrinkled skin. Another unique form is ARCL2A, which is a CL syndrome presenting with reversed skin aging. In contrast, the metabolic CL syndrome ARCL2B frequently presents with progeria, evolving into a CL phenotype with wrinkled skin with further aging. Neurological involvement is very common in CL syndromes, emphasizing the importance of the underlying genes in neurodevelopment and positioning this group of disorders to neurocutaneous syndromes. There are several overlapping symptoms of the diverse types of CL syndromes. However, distinctive laboratory features, such as abnormal glycosylation and specific clinical findings, as cobblestone-like dysgenesis detected by brain imaging, occipital horns on X-ray, or abnormal wrist position with contractures, are discriminative and lead to direct genetic diagnosis.