Tuberous Sclerosis Complex With Renal AML 2

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

THANK YOU