Tuberous Sclerosis With Renal AML
-
Upload
ahmed-ghany -
Category
Health & Medicine
-
view
681 -
download
3
description
Transcript of Tuberous Sclerosis With Renal AML
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.
THANK YOU