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.

Two-fifths of FCPs presented on the forehead, with most of the remainder in other locations on the face and scalp. Better recognition of these lesions may lead to earlier diagnosis of TSC.

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Within Kaiser Permanente Northern California, we identified 128,953 adolescent girls aged 10 to 17 years with a well-child visit during 2012 to 2014. This retrospective study was approved by the institutional review board with a waiver of informed consent. We used measured height and weight to calculate BMI, expressed as BMI percentile. Underweight subjects (BMI less than the fifth percentile) were excluded. Diagnoses of acne (International Classification of Diseases, Ninth Revision code 706.1) within 1 year of the visit were ascertained from pediatrics, family medicine, and dermatology clinic visits. The proportion of patients with diagnosed acne was assessed across 5 BMI percentile categories and stratified by race/ethnicity and age group (Table I). The association of BMI and acne, adjusting for race/ethnicity and age group, was examined with log-binomial regression to estimate relative risk (RR) with 95% confidence intervals (CIs).Among 128,953 adolescent girls (average age 14.0 6 2.3 years), 18.4% were overweight ($85th to \95th BMI percentile) and 15.8% were obese ($95th BMI percentile). The overall proportion of individuals with acne was 17.1%. Acne burden was highest in the upper part of normal BMI but was lower in the overweight and obese ranges (Table I). Adjusting for race/ethnicity and age group (Fig 1), BMI in the lower part of normal was associated with significantly lower risk of diagnosed acne ( fifth to 25th percentile: RR 0.77, 95% CI 0.73-0.81; 25th to 50th percentile: RR 0.90, 95% CI 0.87-0.93) compared with BMI in the upper part of normal (reference group). BMI above normal was also associated with significantly lower risk of diagnosed acne (RR 0.96, 95% CI 0.93-0.99 [overweight]; RR 0.83, 95% CI 0.80-0.86 [obese]).Overweight and obese adolescent girls do not appear to have a higher proportion of acne, even adjusted for race/ethnicity and age, compared with girls in the upper part of normal BMI. Patients in the overweight and obese weight groups may have other health issues that take precedence over acne, or overweight and obese adolescents could have biological factors leading to decreased acne. Limitations include a reliance on acne diagnosis codes and a lack of assessment of puberty status, dietary factors, or acne severity. Although diet and hormonal changes may influence acne, obese and overweight girls in our study had lower rates of diagnosed acne than girls with a BMI in the upper part of the normal range. Future studies could examine the relationship of body weight and acne severity, and referral for dermatology care.

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Background Tuberous sclerosis complex (TSC) is a hamartoma syndrome characterized by multiple skin lesions, such as angiofibromas, shagreen patch and miliary fibromas (MiF).Objective To determine the clinical and histological features of MiF.Methods A retrospective analysis was conducted on 133 adults with TSC. Photography was used to characterize the appearance and location of MiF. Histological features in five skin samples from four individuals were evaluated by a board-certified dermatopathologist. Results MiF were observed in 19 of 133 (14%) individuals with TSC. MiF were 1-to 3-mm skin-coloured, sessile papules scattered on the back and rarely buttocks or thighs. Most were scattered in a bilaterally symmetric distribution, but others were asymmetric or associated with a shagreen patch. Histological features of MiF included expansion of the papillary and periadnexal dermis with variable hamartomatous abnormalities involving adjacent epithelial components.Conclusions MiF are distinct from other cutaneous lesions in TSC such as shagreen patches and angiofibromas.Recognition of this entity is important in defining the spectrum of TSC disease and reassuring individuals with TSC that these lesions are benign.