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. 2019 Dec;81(6):1300-1307.
doi: 10.1016/j.jaad.2019.05.021. Epub 2019 May 11.

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

Majid Arefi  1 , Valerie Wilson  2 , Siobhan Muthiah  3 , Simon Zwolinski  2 , Dalvir Bajwa  1 , Paul Brennan  2 , Katie Blasdale  4 , David Bourn  2 , John Burn  5 , Mauro Santibanez-Koref  1 , Neil Rajan  6
Affiliations

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

Majid Arefi et al. J Am Acad Dermatol. 2019 Dec.

Abstract

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.

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Figures

None
Graphical abstract
Fig 1
Fig 1
Mosaic CYLD cutaneous syndrome. A, Localized clusters of cylindroma or cylindrospiradenoma shown, from left to right, in cases 2, 5, and 6. B, Histopathology of cylindroma (hematoxylin-eosin stain; original magnification: 20). White scale bar indicates 50 μm.
Fig 2
Fig 2
CYLD contiguous deletion syndrome. A, The facial gestalt of the daughter with a germline contiguous gene deletion involving CYLD. B, The 5.5-Mb deletion, indicated within the double-ended red arrows, was validated in the child as present in a heterozygous state and involved CYLD and 23 additional genes.
See this image and copyright information in PMC

References

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