Tuberous sclerosis complex (TSC) is a genetic disorder characterized by benign tumors that develop in many organs, including the brain, skin, eyes, heart, lungs, and kidneys. It is caused by mutations in either the TSC1 or TSC2 gene. Common manifestations include seizures in 80-90% of patients, cognitive deficits in 44-65%, skin lesions in 81-95%, and brain lesions visible on MRI in 90% of patients. Renal angiomyolipomas occur commonly and sometimes cause bleeding. Everolimus has been approved to treat renal angiomyolipomas by reducing their volume. Surveillance every 2 years is recommended due to the progressive nature of TSC.

1. TUBEROUS SCLEROSIS COMPLEX
Ahmed Abdul Ghany

2. INTRODUCTION:
TSC is an inherited neuro-cutaneous disorder characterized by multiple
benign hamartomas of the skin, eyes, brain, heart, lung, kidney and
liver.
In 1862 von Recklinghausen identified heart and brain tumors in a
newborn that had only briefly lived. However, Bourneville (1880) is
credited with having first characterized the disease, thus earning the
eponym Bourneville's disease.

3. GENETICS
• Autosomal dominant with
incidence 1 in 5000 live births.
• Mutation in TSC-1 or TSC-2
genes.
• +ve family history in 7 – 37%

4. Diagnostic criteria
Definite TSC
2 major
1 major + 2 minor
Probable TSC
1 major plus 1 minor
Possible TSC
1 major
2 or more minor

5. DERMATOLOGICAL
LESIONS:
81-95%

6. Angiofibromas
Fibrous plaque

7. Ash leaf spots
Periungual & subangual fibromas

8. BRAIN LESIONS
90%

9. Glioneuronal hamartomas
Subependymal nodules

10. SGCA

11. Clinically (CNS):
• Epilepsy affecting 80 – 90% of patients in the form of infantile
spasms, simple or complex partial seizures with EEG +ve in 75 % of
patients.
• Cognitive deficits 44 – 65%.
• Autism and behavioral problems.

12. Hydrocephalus
New
symptoms or
papilledema
Diagnostic
features
associated with
increase
morbidity
Serial imaging
showing
growth of
lesions

13. RENAL MANIFESTATIONS

14. Renal Angiomyolipomas (AML)
• Common in TSC
patients

15. • Asymptomatic in most cases however symptoms may be
related to bleeding or mass effect.
• 2 histological types: classic and Epithelioid AML
• Diagnosis relies on the demonstration of Fat in the Tumor

17. Prophylactic surgery?
Therapeutic interventions
• size ≥4cm to prevent bleeding
• Nephron sparing surgery
• High vascularity and/or
• Selective renal artery
aneurysm ≥ 5mm.
• High suspicion of malignancy
embolization
• Radiofrequency ablation
• Radical nephrectomy.

18. Potential issues in women
• Female sex hormones promote growth of renal AMLs and
their hemorrhagic complications during pregnancy, thus
frequency of US surveillance should increase.

19. Renal cystic disease
• The 2nd most common renal manifestation in TSC.
• 3 types of renal cysts are associated:
• Singe or multiple renal cysts
• TSC2/PKD1 contiguous gene syndrome
• Glomerulocytic kidney disease.

20. Chronic kidney disease:
• Some TSC patients may develop CKD, subnephrotic
proteinuria, hypertension and ESRD in absence of large
AML.
• Renal biopsy often reveals FSGS.

21. OPHTHALMIC
MANIFISTATIONS

22. • Retinal hamartomas
• Angiofibromas of the eyelid

23. CARDIOPULMONARY

24. Cardiac (Rhabdomyoma)
Pulmonary (LAM)
• Often detected on prenatal US
• Lymphangioleiomyomatosis
• Benign tumor usually undergo
• Manifestations are similar to
spontaneous regression.
those with interstital lung
disease.

25. Management
Everolimus
Pulmonary
cosmetic
Renal AML
Seizure control

26. EVEROLIMUS
• FDA approved mTOR inhibitor (ExIST-2 trial)
• 50% reduction in AML volume in 3 month
• Recommended dose: 10 mg od for 38 weeks
• Reasonable candidates are:
• patients with renal AML plus other organ affected
• Rapidly growing AMLs.
• Patients who underwent nephrectomy or embolization.

27. Prognosis
• TSC is a progressive disorder.
• Causes of death usually due to status epilepticus or renal
disease.
• Surveillance is recommended every 2 years including
mental, physical examination, MRI brain, US and ECHO.

28. THANK YOU