Tuberous Sclerosis

Tuberous sclerosis is a rare multi-system genetic disease that causes non-malignant tumors to grow in the brain, kidneys, heart, eyes, lungs, and skin. It is associated with seizures, mental retardation, skin abnormalities, and lung and kidney disease.

Tuberous Sclerosis: An autosomal dominant genetic neurocutaneous disorder with a diverse presentation that can involve hamartomas in several organ systems including the brain, eye, heart, lung, liver, kidney, and skin.

Epidemiology: The prevalence is 1 in 10,000. Subependymal giant cell tumors usually present between ages 10 and 30.

Clinical Presentation: The classic Vogt’s Triad of mental retardation, seizures, and facial angiofibromas only occurs in one third of patients. 95% of patients present with some form a skin lesion with the most frequent being ash-leaf spots, angiofribromas, shagreen patches, and a brown fibrous plaque on the forehead. Retinal hamartomas are seen in nearly half of all patients but the opthalamic features of this disease rarely impact vision. Cardiac rhabdomyomas are more frequently associated with Tuberous Sclerosis. Angiomyolipomas of the kidneys can cause both hemorrhage and impair renal function. Patients may also develop a pulmonary condition similar to diffuse interstitial fibrosis. Subependymal giant cell tumors are also characteristic of the disease. Patients often also suffer from epilepsy.

Differential Diagnosis: Complex Partial Seizures, Epilepsy, Glioblastoma Multifome, West Syndrome, Lennox Gastaut Syndrome.

Diagnosis: A diagnostic criteria involving major and minor features was adopted in 1998. A definite diagnosis requires either two major features or one major plus two minor features. The eleven major features are: Facial anglofibromas or forehead plaque, Nontraumatic ungual or periungual fibroma,  Hypomelanotic macules, Shagreen patch, Multiple retinal nodular hamartomas, Cortical tuber, Subependymal nodule, Subpendymal glant cell atrocytoma , Cardiac rhabdomyoma, Lymphangiomyomatosis, and Renal angiomyolipoma. The nine minor features include: Multiple randomly distributed pits in dental enamel, Hamartomatous rectal polyps, Bone cysts,  Cerebral white matter radial migration lines, Gingival fibromas, Nonrenal hamartoma, Retinal achromic patch, "Confetti" skin lesions , and Multiple renal cysts.

Treatment: While antiepileptic medications are critical, treatment is usually tailored to the patient’s unique presentation of the various manifestations of Tuberous Sclerosis. 


 Imaging Findings
- Brain MR indicated if clinical suspicion
- Calcified subependymal tubers are characteristic, present in up to 98% of patients
- Cortical or subcortical tubers at juxtacortical junction
- White matter lesions extending to ependyma
- Renal ultrasound at diagnosis and every 1-3 years as renal lesions common
- Renal angiomyolipomas (AML) found in majority of adult tuberous sclerosis patients 
- AMLs characterized by presence of low attenuation intratumor fat, helps distinguish from renal cell carcinoma
- Suspect ruptured AML if hemorrhage present
- Retroperitoneal and pulmonary lymphangioleiomyomatosis can be associated; these are walled-off cystic lesions with honeycomb appearance





Case #1a. Lymphangioleiomyomatosis (LAM) in patient with tuberous sclerosis. LAM results from smooth muscle proliferation causing obstruction of small airways and pulmonary air cyst formation. It can occur sporadically in females, or in association with tuberous sclerosis.

 



Case #1b. Angiomyolipomas in tuberous sclerosis. Proliferation of blood vessels, smooth muscle, and fat (hypodense lesions seen below). The smooth muscle proliferation is histologically identical to that seen in the lungs in lymphangioleiomyomatosis.