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TUBEROUS SCLEROSIS COMPLEX
INTRODUCTION
Skin EyesBrainHeart
Lung Kidney Liver
Tuberous Sclerosis Complex (TSC)inherited neuro-cutaneous disorder multiple benign hamartomas:
GENETICS
Autosomal dominant Incidence 1 : 5000
livebirthsMutation in
TSC-1 (Hamartin) or
TSC-2 (Tuberin)+ve family history in 7 –
37%
Cell Proliferation
complex
hamartinTSC1
tuberinTSC2
Hamartin-Tuberin complexCentral regulator of cell cycle
TSC: loss of inhibition to cell cycle
Diagnostic criteria Major Features
Facial angiofibromas or forehead plaque
Non-traumatic ungual or periungual fibroma
Hypomelanotic macules
Shagreen patch
Multiple retinal nodular hamartomas
Cortical tuber
Subependymal nodule
Subependymal giant cell astrocytoma
Cardiac rhabdomyoma
Lymphangio- myomatosis
Renal angiomyolipoma
Minor Features
Multiple pits in dental
enamel
Hamartomatous rectal
polyps
Bone cysts
Cerebral white matter
migration lines
Gingival fibromas
Non-renal hamartoma
Retinal achromic patch
"Confetti" skin lesions
Multiple renal cysts
Diagnosis
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 LESIONS
90%
Glioneuronal hamartomas
Subependymal nodules
Subependymal Giant Cell tumor
Clinically:
Epilepsy affecting 80 – 90% infantile spasms simple or complex partial seizures EEG +ve in 75 % of patients
Cognitive deficits 44 – 65%
Autism and behavioral problems
Diagnostic features
associated with increase
morbidity
New symptoms
or papilledema
Hydrocephalus
Serial imaging showing growth of lesions
RENAL MANIFESTATIONS
Renal Angiomyolipomas (AML)Frequency in TSC patients: ~ 40 – 70 %
Renal Angiomyolipomas (AML) Asymptomatic in most cases Symptoms
bleeding mass effect
2 histological types: Classic Epithelioid
Diagnosis : demonstration of FAT in the Tumor
Renal Angiomyolipomas (AML)
AML contain fat
Peri-renal fat
Treatment of AML Prophylactic surgery?
Size ≥4cm to prevent bleeding
High vascularity and/or aneurysm ≥ 5mm
High suspicion of malignancy
Treatment of AML 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
Frequency of U/S surveillance should increase
Renal cystic disease The 2nd most common renal
manifestation in TSC 3 types :
Singe or multiple renal cysts TSC2/PKD1 contiguous gene
syndrome Glomerulocytic kidney disease
Chronic kidney diseaseIn absence of large AML, patients may develop:
CKD subnephrotic proteinuria hypertension ESRD
Renal biopsy often reveals FSGS
OPHTHALMIC MANIFESTATIONS
Retinal hamartoma
Calcified hamartoma
CARDIOPULMONARY
Cardiac Rhabdomyoma
detected on prenatal US
Benign tumor usually undergo spontaneous regression
Pulmonary (LAM)
Lymphangio-leiomyomatosis
Manifestations are similar to those with interstitial lung disease
Management
Everolimus
Pulmonary
CosmeticRenal AML
Seizure control
EVEROLIMUS FDA approved mTOR after ExIST-2 trail 50% reduction in AML volume in 3 month Dose : 10 mg od for 38 weeks Candidates :
patients with renal AML plus other organ affected
Rapidly growing AMLs Patients who underwent nephrectomy or
embolization
Cell Proliferation
complex
hamartinTSC1
tuberinTSC2
Hamartin-Tuberin complexCentral regulator of cell cycle
TSC: loss of inhibition to cell cycle
EVEROLIMUS
Prognosis TSC is progressive
Cause of death: status epilepticus renal disease
Surveillance : every 2 years mental, physical examination MRI brain U/S abdomen ECHO
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