Background: Clusters of rare cylindroma or spiradenoma tumors are a recurrent clinical presentation, yet conventional genetic testing results in individuals with these tumors are frequently normal.
Objective: To determine if genetic mosaicism accounts for such cases.
Methods: A study of 6 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 mosaic pathogenic CYLD variants in both the blood and 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 2 patients had clinical features of mosaicism, but these cases were not solved with the assays used because of a lack of access of fresh tumor tissue.
Conclusion: Genetic mosaicism should be considered in patients presenting with clustered cylindromas, because this may inform genetic testing and counseling of these patients.
Keywords: Brooke-Spiegler syndrome; CYLD; CYLD cutaneous syndrome; genetic counseling; genetic testing of the skin; mosaicism; parent-to-child transmission.
Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.