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, 24y, n=7), mosaic patients with bilaterally symmetric facial angiofibromas (8 findings, 10y, n=12), and germline TSC patients (10 findings, 4y, 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.

Skin lightening (SL) for cosmetic reasons is associated with profound negative impacts on well-being and adverse effects on the skin, resulting in immense challenges for dermatologists. Despite current regulations, lightening agents continue to dominate the cosmetic industry. In this review, our international team of dermatologists tackles the topic of SL as a global public health issue, one of great concern for both women’s health and racial implications. We have examined SL in Africa, Asia, the Middle East, and the Americas. We aim to inspire a global discourse on how modern dermatologists can utilize scientific evidence and cultural competency to serve and protect patients of diverse skin types and backgrounds. In doing so, we hope to promote healthy skin and inclusive concepts of beauty in our patients and society.