Genotypic and phenotypic features of 23 Egyptian patients with tuberous sclerosis complex

Tuberous sclerosis complex (TSC) is a multisystem disease caused by pathogenic variants in TSC1 or TSC2 genes. Although features of TSC have been described in various populations, genetic data from Egypt remain scarce. This study aimed to characterize the phenotypic and molecular features of TSC among a cohort of Egyptian patients.

This observational study included patients clinically diagnosed with TSC at two Egyptian centers between 2022 and 2025. All participants underwent a comprehensive evaluation, including demographic profiling, clinical assessment, imaging studies, and whole-exome sequencing. Identified TSC1 and TSC2 variants were cross-referenced with public databases, analyzed using bioinformatics tools, and classified according to the American College of Medical Genetics and Genomics guidelines.

The cohort contained 23 cases from 20 unrelated families (16 males and 7 females; median age: 8.1 years). Parental consanguinity and positive family history were present in 13 and 12 cases, respectively. The median age at initial presentation was 8 months (interquartile range: 3-24 months). Patients exhibited various manifestations, including hypomelanotic macules (100%), cortical tubers (96%), seizures (87%), TSC-associated neuropsychiatric disorders (78%), facial angiofibromas (65%), shagreen patches (48%), renal angiomyolipomas (44%), and cardiac rhabdomyomas (39%). Eighteen distinct variants were identified (16 in TSC2, 2 in TSC1), including nine novel variants. These comprised nine deletions/insertions, five splice-site, three nonsense, and one missense variant. Most variants (89%) were "private", each observed in a single family.

This study provides the first comprehensive genetic analysis of TSC in Egypt. The findings expand the demographic, phenotypic, and genetic spectrum of TSC in an underrepresented population.