Description of the natural course and clinical manifestations of ichthyosis with confetti caused by a novel KRT10 mutation

Abstract

Ichthyosis with confetti (IWC) was first described as ichthyose en confettis and subsequently as congenital reticular ichthyosiform erythroderma. Because of the development of hundreds to thousands of pale, normal-appearing confetti-like spots during childhood, the disease was named IWC. Patients with IWC show erythroderma, prominent scaling and palmoplantar keratoderma. Our female index patient was described in 1990 as the fourth patient reported worldwide; at that time she did not show any confetti-like spots. She was periodically examined at our clinic from birth until adulthood; hence we are able to describe the natural course of IWC in detail for the first time. We furthermore identified two novel deletions in KRT10, one of them leading to a frameshift and consequently to an arginine tail of keratin 10. Our report is the first independent confirmation of the KRT10 gene defect and revertant mosaicism mechanism in patients with IWC and it expands the clinical findings.

Early Immunopathological Diagnosis of Ichthyosis with Confetti in Two Sporadic Cases with New Mutations in Keratin 10

“…2b, c). These findings, similar to those recently reported in IC patients, were considered highly suggestive for IC (6,9). Furthermore, molecular analysis of KRT10 gene in the patient and her parents identified a de novo deletion, c.1383_1414del32 (p.Gly462_Gly472>Glyfs109), in exon 7, in linkage with the c.1468_1479del12 (p.Gly490_Gly493del) in-frame variant inherited from the father (Fig.…”

“…Indeed, in Case 1 the revertant skin spots became evident after starting the treatment with acitretin, similarly to what was described in one of the original cases by Camenzind et al (2). Overall these observations further support the theory 1 http://www.medicaljournals.se/acta/content/?doi=10.2340/00015555-1796 that the reverse mutations could start already in foetal life and that the progressive enlargement and growth advantage of revertant epidermal cell clones could lead to the appearance of the first revertant spots detectable, if carefully searched for, even in infancy (8,9).…”

“…All identified mutations result in mutant mRNA transcripts encoding polypeptides that are arginine-enriched in their C-terminus and that abnormally accumulate within the nucleolus (8,9). Of note, IC represents the most impressive example of revertant mosaicism as each normal appearing skin patch corresponds to an independent event of somatic reversion.…”

“…Of note, IC represents the most impressive example of revertant mosaicism as each normal appearing skin patch corresponds to an independent event of somatic reversion. The mechanism of reversion is mitotic recombination leading to loss of heterozygosity (8,9).…”

Pityriasis Rubra Pilaris: Treatment with Biologics – A New Promising Therapy?

“…Between lesional plaques one can typically see islands of normal-appearing skin recognized as ‘nappes claires’. The spared skin lesions could hypothetically reflect any form of backmutation in a polygenic disease similar to ichthyosis en confetti [10]. Palms and soles are usually involved, and orange waxy keratoderma predominates.…”