Deep phenotyping of patients with Tuberous Sclerosis Complex and no mutation identified in TSC1 and TSC2

Tuberous Sclerosis Complex (TSC) is a multisystemic condition caused by mutations in TSC1 or TSC2, but a pathogenic variant is not identified in up to 10% of the patients. The aim of this study was to delineate the phenotype of pediatric and adult patients with a definite clinical diagnosis of TSC and no mutation identified in TSC1 or TSC2. We collected molecular and clinical data of 240 patients with TSC, assessing over 50 variables. We compared the phenotype of the homogeneous group of individuals with No Mutation Identified (NMI) with that of TSC patients with a TSC1 and TSC2 pathogenic variant. 9.17% of individuals were classified as NMI. They were diagnosed at an older age (p = 0.001), had more frequent normal cognition (p