Phenotypic distinctions between mosaic forms of tuberous sclerosis complex

Alison M. Treichel, Lana Hamieh, Neera R. Nathan, Magdalena E. Tyburczy, Ji an Wang, Oyetewa Oyerinde, Sorana Raiciulescu, Patricia Julien-Williams, Amanda M. Jones, Vissaagan Gopalakrishnan, Joel Moss, David J. Kwiatkowski, Thomas N. Darling*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


Purpose: To determine if mosaic tuberous sclerosis complex (TSC) can be stratified into subtypes that correspond with prognosis and extent of disease. Methods: Next-generation sequencing of skin tumor and other samples was used to identify patients with mosaic pathogenic variants in TSC1 or TSC2. Extent of disease, onset age, and family history of TSC were determined through retrospective analysis of patient records. Results: The median number of disease findings and age at penetrance differed between mosaic patients with asymmetrically distributed facial angiofibromas (4 findings, 24 years, n = 7), mosaic patients with bilaterally symmetric facial angiofibromas (8 findings, 10 years, n = 12), and germline TSC patients (10 findings, 4 years, n = 29). Cutaneous and internal organ involvement positively correlated in mosaic (R = 0.62, p = 0.005), but not germline (R = −0.24, p = 0.24) TSC. Variant allele fraction (VAF) in the blood (range: 0–19%) positively correlated with the number of major features (R = 0.55, p = 0.028). Five had a TSC2 variant identified in the skin that was below detection in the blood. One of 12 children from a mosaic parent had TSC. Conclusion: The phenotype of mosaic TSC ranged from mild to indistinguishable from germline disease. Patients with mosaicism and asymmetric facial angiofibromas exhibited fewer findings, later onset, and lower VAF in the blood.

Original languageEnglish
Pages (from-to)2594-2604
Number of pages11
JournalGenetics in Medicine
Issue number11
StatePublished - 1 Nov 2019
Externally publishedYes


  • angiofibroma
  • genodermatosis
  • mosaic
  • segmental
  • tuberous sclerosis complex


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