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

Possible TSC

1 major 2 or more minor

Probable TSC1 major plus 1 minor

Definite TSC2 major 1 major + 2 minor

DERMATOLOGICAL LESIONS:81-95%

Angiofibromas Fibrous plaque

Ash leaf spots Periungual & subangual fibromas

BRAIN LESIONS90%

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.

Diagnostic features

associated with increase morbidity

New symptom

s or papillede

ma

Hydrocephalus

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

Prophylactic surgery?

• size ≥4cm to prevent bleeding

• High vascularity and/or aneurysm ≥ 5mm.

• High suspicion of malignancy

Therapeutic interventions

• Nephron sparing surgery

• Selective renal artery 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)

• Often detected on prenatal US• Benign tumor usually undergo

spontaneous regression.

Pulmonary (LAM)

• Lymphangioleiomyomatosis• Manifestations are similar to

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.

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