A dermatological assessment of pediatric patients with tuberous sclerosis complex (TSC)

Abstract

Background: Tuberous sclerosis complex (TSC) is a multisystem neurocutaneous syndrome with variable phenotypes. Recent updates of TSC diagnostic criteria reaffirmed the defined genetic diagnostic criterion as the finding of a pathogenic DNA alteration in either TSC1 or TSC2 genes. It also slightly modified definite clinical diagnostic criteria. TSC-associated skin lesions in infancy are important clinical signs to select individuals with possible TSC for a closer clinical follow-up and genetic testing.

Objective: To raise awareness of the updated TSC diagnosis criteria; to assess the frequency of skin lesions in TSC patients as well as the first dermatological presentation; and to associate the findings with either TSC1 or TSC2 mutations.

Methods: Observational cross-sectional study. Clinical and genetic data were retrospectively collected from 37 TSC patients from a Brazilian University Hospital. Patients with skin signs were examined and prospectively assessed for 12 months.

Results: The earliest cutaneous lesions were hypomelanotic macules, which together with angiofibromas were the most frequent dermatological lesions. The total pathogenic DNA alteration ratio between TSC2 and TSC1 genes was 8:1. The frequency of a TSC2 pathogenic variant was 10-fold greater in the presence of ungual fibromas.

Study limitations: Small sample and a limited number of patients with TSC1 pathogenic variants.

Conclusion: Clinicians should be knowledgeable about TSC updated diagnostic criteria. Patients need to be followed up by a multidisciplinary team and treated accordingly. Early detection of cutaneous lesions is important for TSC diagnosis. A significant association between TSC2 gene pathogenic alterations and ungual fibromas is described.

Keywords: Genetic diseases; Neurocutaneous syndromes; Tuberous Sclerosis Complex 1 gene; Tuberous Sclerosis Complex 2 gene; Tuberous sclerosis complex.