Diverse presentations of cutaneous mosaicism occur in CYLD cutaneous syndrome and may result in parent to child transmission

Abstract Background Clusters of rare cylindromaor spiradenomatumors are a recurrent clinical presentation, yet conventional genetic testingin these individuals is frequently normal. Objective To determine if genetic mosaicismaccounts for such cases. MethodsA study of six cases from a series of 55 patients who met criteria for diagnostic gene testing for pathogenic CYLD variants over a 5-year period (2012-2017) was performed. A novel genetic assay was used to study DNA from peripheral blood leukocytes, and where possible, matched skin and tumor tissue. Results Two patients had mosaicpathogenic CYLD variants in both blood and the skin. One of these patients transmitted a pathogenic variant to her daughter, and we report the novel phenotype of a contiguous gene deletion syndrome involving CYLD . Two patients had recurrent pathogenic variants in skin tumors from a single cluster, but none detectable in the blood. Limitations The remaining two cases had clinical features of mosaicism, but were not solved using the assays employed, due to the lack of access of fresh tumor tissue. Conclusion Genetic mosaicismshould be considered in patients presenting with clustered cylindromasas this may inform genetic testingand counselling of these patients.