Mortality in Tuberous Sclerosis Complex in the United Kingdom, 2016-2022

Tuberous sclerosis complex (TSC) is a genetic condition caused by mutations in either TSC1 or TSC2 genes, affecting around two million people globally. This study aims to examine causes of death in TSC and explore factors contributing to mortality in people with TSC in the United Kingdom in recent years following updated management and surveillance guidelines for the condition.

Comprehensive analysis of the available medical records of the people seen at the largest lifespan TSC clinic in the United Kingdom who passed away between 2016 and 2022 was conducted. Disease-related factors were identified, and the cause of death was determined. Where mortality cause was unobtainable, information was sought from the person's general practitioner, or their death certificate was obtained from the General Registry Office. Subsequently, the cohort was divided into subgroups to investigate potential risk factors for premature mortality. Our results were compared to that of previous TSC mortality studies.

The study consisted of 19 deaths. Nine deaths were unequivocally attributed to TSC. These fatalities were due to epilepsy (n = 3/19), aspiration pneumonia (n = 3/19), SEGA (n = 1/19), hepatic AML (n = 1/19) and pNET (n = 1/19). Other causes included malignant cancer (n = 6/19), sepsis (n = 2/19), COVID-19 (n = 1/19) and stroke (n = 1/19). Renal failure was a secondary cause in two deaths.

Compared to limited previous mortality studies, this cohort appears to be less affected by SUDEP. This group is also more greatly affected by cancer and presents a potential link between early mortality and renal AML size. Moreover, a clearer role of intellectual disability in mortality of people with TSC may have been identified. Most causes of mortality in this TSC cohort are potentially prevented with suitable interventions earlier.