Management of Tuberous Sclerosis Complex

Introduction to TSC Management

The American College of Nephrology recommends a coordinated multidisciplinary approach for the management of tuberous sclerosis complex, involving specialists from neurology, nephrology, pulmonology, dermatology, and other disciplines to address the multiple organ systems affected by this condition and reduce morbidity and mortality 1, 2
All patients with TSC should be referred to an expert center with a multidisciplinary team to coordinate care across multiple affected organ systems 1, 2
Regular follow-up should occur at least annually with specialists relevant to the patient's specific manifestations 2
A transition plan from pediatric to adult care should be established, including specified age of transition, process steps, and identification of adult healthcare professionals 3

Monitor for and treat epilepsy, which is a leading cause of mortality in TSC patients 1

Regular kidney monitoring is essential as kidney disease is the most common cause of death in adults with TSC 1
Monitor for three major kidney phenotypes: angiomyolipomata, cystic disease, and renal cell carcinoma 1, 4
Begin kidney monitoring from the point of diagnosis, even in young children, as both cysts and angiomyolipomata can develop in the first months of life 5
For angiomyolipomata, consider arterial embolization as the first-line approach for actively bleeding lesions 6, 7
Consider preventive arterial embolization for asymptomatic angiomyolipoma >4 cm, especially those with rich angiomatous content 7
Partial nephrectomy should be considered when embolization fails or is unavailable 7

Annual standardized office blood pressure measurements for all patients 8
24-hour ambulatory blood pressure monitoring if BP ≥120/70 mmHg in adults 8
Annual assessment of kidney function and proteinuria in adults and children with kidney involvement on imaging 8
First-line treatment for hypertension: ACE inhibitors or ARBs 8
Consider SGLT2 inhibitors for patients with CKD progression, even though specific evidence in TSC population is limited 8

Consider immunosuppressive regimens containing an mTOR inhibitor after kidney transplantation in patients with TSC-associated phenotypes known to respond to mTOR inhibition 7

Monitor for proteinuria, which may develop or worsen with mTOR inhibitor therapy 8

Discuss genetic screening with family members 2
Family members with TSC clinical features should be screened for the relevant pathogenic variant if known 2
Genetic testing has limited value in family members with no clinical features of TSC 2

TSC is often not recognized by clinicians without specialist knowledge, as <40% of patients have the classic triad of facial angiofibromata, developmental delay, and intractable epilepsy 1
Normal kidney imaging and GFR in young children do not preclude future development of kidney lesions 5
In patients with low muscle mass due to severe neurological complications, standard creatinine-based equations can overestimate eGFR; consider cystatin C-based equations 9
Avoid nephron loss during interventional procedures by ensuring effective targeting of angiomatous arteries and avoiding non-target embolization 7