Many of the TSC clinics in the United States are headed by neurologists, which is fairly telling in that the neurologic manifestations of TSC are significant and very impactful. In fact, the central nervous system is among the most commonly affected systems in TSC. The burden can be felt early in life with infantile spasms, and the impacts may be profound and lifelong. TSC-associated epilepsy affects many patients, causing significant morbidity and, rarely, sudden unexpected death in epilepsy. The involvement of other organ systems in those with TSC can also carry a risk of significant morbidity and may contribute to mortality; for example, renal angiomyolipoma and lymphangioleiomyomatosis are important causes of TSC-related mortality in adults. 

In addition to the significant burden from epilepsy among those with TSC, there is a growing awareness of the burden from TSC-associated neuropsychiatric disorders (TAND). When you look at the TSC patient community, I think that epilepsy followed by TAND are probably at the top of the list in terms of concerning issues. 

Interpersonal relationships can be very difficult for people with TSC and can include problems at school for children with TSC. Some children with the disorder have so many issues at school that they have to be homeschooled, and these problems may begin even prior to receiving a diagnosis of TSC for some individuals. A child with TAND may have to enter the classroom before anyone else, every morning, as a strategy to combat school phobia. And a diagnosed or an undiagnosed parent of that child with TSC might relate to this feeling of school phobia, having had similar experiences during their own childhood. An adult in their 40s or 50s may be living their life with TSC, experiencing significant impacts from TAND, without ever actually knowing that they have TSC, and I suspect that TAND is still underdiagnosed and undertreated in adults, despite the growing recognition. 

SEGAs, which develop in approximately 10% to 20% of people with TSC, represent an area in which we have made substantial progress. When we know that a child has TSC, we can follow them, ensuring that they have annual imaging so that these tumors can be detected and managed. For unknown reasons, SEGAs stop growing around ages 20 to 25 years. When SEGAs develop and grow, especially in children who are not known to have TSC, they may contribute to mortality by causing obstructive hydrocephalus and, potentially, herniation, so this is another possible contributor to TSC-associated mortality.

In summary, the neurologic and neuropsychiatric morbidity of TSC can be quite high. Uncontrolled epilepsy and infantile spasms, TAND, the neurobehavioral aspects of TSC, and SEGAs can each have a significant impact on the rest of the individual's life.