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TUBEROUS SCLEROSIS COMPLEX

Ahmed Abdul Ghany
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.
GENETICS
• Autosomal dominant with

incidence 1 in 5000 live births.
• Mutation in TSC-1 or TSC-2
genes.
• +ve family history in 7 – 37%
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
DERMATOLOGICAL
LESIONS:
81-95%
Angiofibromas

Fibrous plaque
Ash leaf spots

Periungual & subangual fibromas
BRAIN LESIONS
90%
Glioneuronal hamartomas

Subependymal nodules
SGCA
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.
Hydrocephalus
New
symptoms or
papilledema

Diagnostic
features
associated with
increase
morbidity
Serial imaging
showing
growth of
lesions
RENAL MANIFESTATIONS
Renal Angiomyolipomas (AML)
• Common in TSC

patients
• 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
Tuberous Sclerosis With Renal AML
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.
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.
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.
Chronic kidney disease:
• Some TSC patients may develop CKD, subnephrotic

proteinuria, hypertension and ESRD in absence of large
AML.
• Renal biopsy often reveals FSGS.
OPHTHALMIC
MANIFISTATIONS
• Retinal hamartomas
• Angiofibromas of the eyelid
CARDIOPULMONARY
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.
Management

Everolimus

Pulmonary

cosmetic

Renal AML

Seizure control
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.
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.
THANK YOU

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Tuberous Sclerosis With Renal AML

Editor's Notes

  1. M tor : mailman target of rapamycin