What is the management approach for tuberous sclerosis complex (TSC)?

Management of Tuberous Sclerosis Complex (TSC)

The management of tuberous sclerosis complex requires a coordinated multidisciplinary team approach in specialized centers to address multiple organ system involvement, with regular monitoring and targeted interventions to reduce morbidity and mortality. 1

Multidisciplinary Care Approach

• All patients with TSC should be referred to an expert center with a multidisciplinary team to coordinate care across multiple affected organ systems 1
• Structured multidisciplinary follow-up visits should be offered, ideally scheduling multiple specialty appointments on the same day when possible 2
• A three-step approach is recommended for establishing multidisciplinary care:
  • Step 1: Identify a single individual to begin organizing care
  • Step 2: Establish a small core team
  • Step 3: Develop a larger multidisciplinary team 3
• A designated case manager should help coordinate care between specialists 3

Essential Specialists in TSC Management

• Nephrologist: Critical for monitoring kidney involvement, which is the most common cause of death in adults with TSC 2, 1
• Neurologist: For management of epilepsy and neurological manifestations 1
• Pulmonologist: Particularly important for patients with lymphangioleiomyomatosis 1
• Dermatologist: For management of cutaneous manifestations 1
• Psychiatrist/Psychologist: For TSC-associated neuropsychiatric disorders 1, 3
• Additional specialists as needed: Ophthalmologist, cardiologist, geneticist, urologist, neurosurgeon 3

Kidney Monitoring and Management

• Begin kidney monitoring from the point of diagnosis, even in young children 1
• Regular monitoring for three major kidney phenotypes: angiomyolipomata, cystic disease, and renal cell carcinoma 1
• For angiomyolipomata:
  • Consider arterial embolization as first-line approach for actively bleeding lesions 1
  • Consider preventive arterial embolization for asymptomatic angiomyolipoma >4 cm 1
  • Partial nephrectomy should be considered when embolization fails or is unavailable 1
• Nephron-sparing strategies are essential considering the multiplicity and recurrent nature of kidney tumors in TSC 2
• Annual assessment of kidney function and proteinuria in adults and children with kidney involvement 1

Pharmacological Management

• mTOR inhibitors (e.g., everolimus) are indicated for:
  • Treatment of renal angiomyolipoma in adult patients with TSC not requiring immediate surgery 4
  • Treatment of subependymal giant cell astrocytoma (SEGA) in patients aged 1 year and older with TSC 4
• The recommended dosage of everolimus for TSC-associated renal angiomyolipoma is 10 mg orally once daily until disease progression or unacceptable toxicity 4
• For TSC-associated SEGA, the recommended starting dosage is 4.5 mg/m² orally once daily 4
• Monitor everolimus whole blood trough concentrations and titrate to attain trough concentrations of 5-15 ng/mL 4
• Monitor for and manage adverse reactions, particularly non-infectious pneumonitis and stomatitis 4

Blood Pressure Management

• Annual standardized office blood pressure measurements for all patients 1
• 24-hour ambulatory blood pressure monitoring if BP ≥120/70 mmHg in adults 1
• First-line treatment for hypertension: ACE inhibitors or ARBs 1
• Diagnosis and monitoring of hypertension should be conducted by a (pediatric) nephrologist 2

Transition from Pediatric to Adult Care

• Establish a transition plan from pediatric to adult care 1
• Include specified age of transition, process steps, and identification of adult healthcare professionals 1

Family Screening and Genetic Counseling

• Discuss genetic screening with family members 1
• Family members with TSC clinical features should be screened for the relevant pathogenic variant if known 1
• Genetic testing has limited value in family members with no clinical features of TSC 1

Pitfalls and Caveats

• 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 1
• In patients with low muscle mass due to severe neurological complications, standard creatinine-based equations can overestimate eGFR; consider cystatin C-based equations 1
• Avoid nephron loss during interventional procedures 1
• Monitor for proteinuria, which may develop or worsen with mTOR inhibitor therapy 1, 4