tuberous sclerosis complex with renal aml 2
TRANSCRIPT
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TUBEROUS SCLEROSIS COMPLEX
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INTRODUCTION
Skin EyesBrainHeart
Lung Kidney Liver
Tuberous Sclerosis Complex (TSC)inherited neuro-cutaneous disorder multiple benign hamartomas:
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GENETICS
Autosomal dominant Incidence 1 : 5000
livebirthsMutation in
TSC-1 (Hamartin) or
TSC-2 (Tuberin)+ve family history in 7 –
37%
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Cell Proliferation
complex
hamartinTSC1
tuberinTSC2
Hamartin-Tuberin complexCentral regulator of cell cycle
TSC: loss of inhibition to cell cycle
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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
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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
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Diagnosis
Possible TSC
1 major 2 or more minor
Probable TSC1 major plus 1 minor
Definite TSC2 major 1 major + 2 minor
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DERMATOLOGICAL LESIONS:
81-95%
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Angiofibromas
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Fibrous plaque
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Ash leaf spots
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Periungual & subangual fibromas
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BRAIN LESIONS
90%
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Glioneuronal hamartomas
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Subependymal nodules
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Subependymal Giant Cell tumor
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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
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Diagnostic features
associated with increase
morbidity
New symptoms
or papilledema
Hydrocephalus
Serial imaging showing growth of lesions
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RENAL MANIFESTATIONS
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Renal Angiomyolipomas (AML)Frequency in TSC patients: ~ 40 – 70 %
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Renal Angiomyolipomas (AML) Asymptomatic in most cases Symptoms
bleeding mass effect
2 histological types: Classic Epithelioid
Diagnosis : demonstration of FAT in the Tumor
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Renal Angiomyolipomas (AML)
AML contain fat
Peri-renal fat
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Treatment of AML Prophylactic surgery?
Size ≥4cm to prevent bleeding
High vascularity and/or aneurysm ≥ 5mm
High suspicion of malignancy
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Treatment of AML Therapeutic interventions
Nephron sparing surgery
Selective renal artery embolization
Radiofrequency ablation
Radical nephrectomy
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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
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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
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Chronic kidney diseaseIn absence of large AML, patients may develop:
CKD subnephrotic proteinuria hypertension ESRD
Renal biopsy often reveals FSGS
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OPHTHALMIC MANIFESTATIONS
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Retinal hamartoma
Calcified hamartoma
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CARDIOPULMONARY
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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
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Management
Everolimus
Pulmonary
CosmeticRenal AML
Seizure control
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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
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Cell Proliferation
complex
hamartinTSC1
tuberinTSC2
Hamartin-Tuberin complexCentral regulator of cell cycle
TSC: loss of inhibition to cell cycle
EVEROLIMUS
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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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THANK YOU