Disease relevance of Cutis Laxa

• The phenotypic abnormalities recently observed in a fibulin-5 knockout mouse model are reminiscent of human AR cutis laxa type I. Both share cutis laxa, lung emphysema and arterial involvement [1].
• Autosomal dominant cutis laxa with severe lung disease: synthesis and matrix deposition of mutant tropoelastin [2].
• Sweet's syndrome leading to acquired cutis laxa (Marshall's syndrome) in an infant with alpha 1-antitrypsin deficiency [3].
• With aging, the phenotype has changed significantly: cutis laxa disappeared, the perianal creases and hypotonia are much milder, the initial apparent macrocephaly turned out to be true microcephaly, broad thumbs are less evident, but skeletal anomalies are more striking [4].
• Post-inflammatory elastolysis and cutis laxa (Marshall, Heyl & Weber, 1966) is a skin disease in African infants which appears to be comparatively common in at least two countries [5].

High impact information on Cutis Laxa

• Are X-linked cutis laxa and Menkes disease allelic [6]?
• X-linked cutis laxa: defective cross-link formation in collagen due to decreased lysyl oxidase activity [7].
• This phenotype, which resembles the cutis laxa syndrome in humans, reveals a critical function for fibulin-5 as a scaffold protein that organizes and links elastic fibres to cells [8].
• Skin fibroblasts from two cases of autosomal recessive cutis laxa (CL), having insignificant elastin production and mRNA levels, were challenged with transforming growth factor beta-1 (TGF-beta 1) [9].
• Transforming growth factor-beta reverses a posttranscriptional defect in elastin synthesis in a cutis laxa skin fibroblast strain [9].

Chemical compound and disease context of Cutis Laxa

• Congenital cutis laxa and maternal D-penicillamine [10].
• Cutis laxa and low serum zinc after antenatal exposure to penicillamine [11].
• A 10-year-old boy developed cutis laxa while receiving isoniazid therapy; no systemic manifestations occurred [12].

Biological context of Cutis Laxa

• Genetic heterogeneity of cutis laxa: a heterozygous tandem duplication within the fibulin-5 (FBLN5) gene [13].
• Fibroblast cultures were established from six patients with cutis laxa, and elastin gene expression was analyzed by RNA hybridizations with a 2.5-kilobase human elastin cDNA or an exon 1-specific 35-base oligomer [14].
• Based on a previous observation of an abnormal transferrin isoelectric focusing pattern in a patient with cutis laxa indicating an N-glycosylation defect, we performed a screening for disorders of protein glycosylation in unrelated children with cutis laxa syndrome, including a recently developed test for defective O-glycosylation [15].
• Autosomal dominant cutis laxa, a primarily cutaneous condition, is the result of frameshift mutations at ELN that cause a dominant-negative effect on elastic fiber structure [16].
• Recent evidence indicates cutis laxa fibroblasts that express little or no elastin have normal transcriptional activity but abnormal rates of elastin mRNA degradation [17].

Anatomical context of Cutis Laxa

• Inflammatory destruction of elastic fibers in acquired cutis laxa is associated with missense alleles in the elastin and fibulin-5 genes [18].
• We report a chromosomally normal infant boy with congenital diffuse cutis laxa, severe micrognathia, contractures of all limbs, and central nervous system abnormalities including agenesis of the corpus callosum, born to a woman taking D-penicillamine (DP) for Wilson disease (WD) throughout her pregnancy [19].

Gene context of Cutis Laxa

• As such, we provide evidence that a genetic defect in fibulin-5 (FBLN5, also known as EVEC or DANCE) is responsible for a recessive form of cutis laxa in humans [1].
• CONCLUSIONS: A deficiency of alpha 1-AT may allow proteases such as neutrophil elastase to destroy dermal elastin and, thus, produce cutis laxa in Marshall's syndrome [3].
• Other cases of acquired cutis laxa should be screened for alpha 1-AT deficiency to further evaluate this association and to enable patients and their families to be counseled about possible systemic complications of alpha 1-AT deficiency [3].
• Abnormalities of fibrillin in acquired cutis laxa [20].
• Cutis laxa and the Costello syndrome [21].

Analytical, diagnostic and therapeutic context of Cutis Laxa

• Costello syndrome is emerging as a better delineated condition and should be included in the differential diagnosis of cutis laxa in association with postnatal growth retardation and developmental delay [22].

References