Ichthyosis with confetti (IWC) is a genodermatosis characterized by congenital erythroderma and the systematic development of epidermal pale spots not described in other genodermatoses. All IWC patients are carriers of a heterozygous keratin (KRT)10 or KRT1 variant leading to a shifted reading frame and the translation of an aberrant carboxyl (C)-terminus. The aberrant KRT10/KRT1 protein is localized in the nucleus instead of the cytoplasm. 20 years ago, 2 patients with an IWC-like phenotype were described to suffer from MAUIE (micropinnae, alopecia universalis, ichthyosis, ectropion) syndrome. They showed the typical IWC-phenotype with erythroderma and especially the development of numerous epidermal pale spots. Additionally, both patients had alopecia and developed aggressive and fatal cutaneous squamous cell carcinoma (cSCC). Sequencing was not done at the time. We aimed to verify a possible connection between MAUIE syndrome and IWC.
We isolated gDNA from FFPE-tissues of both patients. We performed NGS and screened for variants similar to IWC-associated variants. A heterozygous KRT10 variant, encoding for an aberrant C-terminus, was identified in each patient and confirmed by Sanger. Nuclear localization of KRT10 was confirmed by immunofluorescence in the patients’ keratinocytes.
We showed that the MAUIE patients had suffered from a specific form of IWC, accompanied by the development of aggressive cSCC. The cause for cancer development is still unclear. The knowledge that the MAUIE patients were carriers of an IWC-associated KRT10 variant emphasizes the importance of skin cancer screening in IWC-patients. We recommend a regular intensive skin examination for cancers and a good education.

Patients with MAUIE syndrome are carriers of heterozygous IWC-associated KRT10 variants