Tuberous sclerosis in Piedmont: a 15-years longitudinal analysis

Tuberous Sclerosis Complex (TSC), is an autosomal dominant rare disease marked by the formation of benign tumors in multiple organs due to mutations in the TSC1 or TSC2 genes. TSC affects approximately 1.5 million people globally, with an annual incidence of 1 in 6,000 to 1 in 10,000 live births, and a prevalence of 1 in 20,000. Our research focused on epidemiology of TSC in both adult and pediatric patients, providing insights into prevalence, incidence and distribution to inform management strategies. This population-based study was conducted using the Piedmont and Aosta Valley Registry of Rare Diseases, focusing on TSC from 2005 to 2023. Employing a retrospective cohort design, the study gathered and analyzed data on TSC patients to explore the disease's epidemiology within these regions. Our study analyzed data from 168 patients diagnosed with TSC. This cohort exhibited a slight male predominance with an overall mean age of 29.38 years (SD: 20.67 years) by the end of 2023. At diagnosis, the mean age was 20.55 years (SD: 31.56 years), with a median of 5 years. Epidemiologically, we observed fluctuating annual reporting rates of TSC, with a notable increase in cases from the 1950s to the 2010s. The estimated incidence varied from 0.02 to 1.11 per 1,000,000 inhabitants, with a 2023 prevalence of 35.03 cases per million, higher in males (40.9 cases per million) than in females (33.4 cases per million). Diagnostic analysis revealed a median age of diagnosis at 3 years, with an average diagnostic delay of 5.09 years (SD: 9.122 years). A positive correlation was found between diagnostic delay and age at diagnosis, suggesting less delay in those diagnosed earlier. Special attention to transitions from pediatric to adult care and the role of various specialists in diagnosis highlighted the complex care needs of TSC patients, underscoring the necessity for a multidisciplinary approach. The advancements in diagnostic technologies and medical management are factors contributing to the observed increase in TSC incidence and underscores the importance of reducing diagnostic delays through heightened disease awareness among physicians and the growing complexities in transitioning TSC patients from pediatric to adult care, stressing the need for improved healthcare infrastructure and knowledge expansion to accommodate the evolving needs of the TSC patient population across their lifespan. Our study acknowledges limitations such as potential underestimation of prevalence due to undiagnosed mild cases and selection bias from using a regional registry, emphasizing the need for broader diagnostic criteria and improved reporting systems to enhance disease recognition and epidemiological understanding.