TUBEROUS SCLEROSIS (TSC)

What does the name mean?

Tuber= swelling (Latin) Skleros= hard (Greek)

What is Tuberous Sclerosis?

-RARE multi-systemic disease causing benign tumors to grow in brain, kidneys, heart, eyes, lungs, skin.

-1/5,000-1/10,000 born with TSC

-Commonly affects CNS resulting in seizures, developmental delay, behavior problems, skin abnormalities, kidney disease.

How can you get this disease? TSC is described as a genetic disease, despite the fact that only 30% of the cases are familial.

-Mutations in TSC1 or TSC2 (chromosome 9) are known causes for TSC

-Hamartin (TSC1) and tuberin (TSC2) are proteins that are missing in the disease leading to unregulated loss of tumor suppression

Inheritance

1 .Genetic autosomal dominant pattern- 100% penetrance 30%

2. Sporadic mutations 70%

3. Gonadal mosaicism- RARE

What are the signs and symptoms? TSC affects many different organ systems which cause a variation in disease presentation.

Physical manifestations due to:

-Hamartia formation (cortical tubers)

-Hamartomas (benign growths)

-Cancerous hamartoblastomas- RARE

CNS	-Learning disability (50%)- autism, ADHD -Subependymal nodules, cortical/subcortial tumors
Kidneys	-Angiomyolipomas (60-80%), renal cysts -Renal cell carcinoma (rare)
Lungs	-Lymphangioleiomyomatosis (lung parenchyma replacement with cysts)
Heart	-Rhabdomymomas (50%)
SKIN	Dermatologic sign= 95% of TSC -Facial angiofibromas, periungual fibromas, hypomelanic macules, forehead plaques, Shagreen patches
Eyes	-Astrocytic hamartomas (retinal) -Coloboma, angiofibromas of eyelids, papilledema

How can I make a diagnosis?

*Most important presentation is infantile spasms (seizures) but remember than many TSC cases can be asymptomatic and do not present until later in their course

Vogt’s Triad= classical diagnostic triad < 50% of patients

1. Seizures (80%)
2. Mental retardation
3. Facial angiofibromas

Major Features	Minor Features
Facial angiofibromas/forhead plaque Shagreen patch Hypomelanotic macules (Ash leaf spots) Periungual fibromas Lymphangiomyomatosis Renal angiomyolipoma Cardiac rhabdomyoma Retinal nodular hamartomas Cortical tuber Subependymal nodules Subependymal giant cell astrocytoma	Confetti skin (multi hypopigment) Gingival fibromas Dental enamel pits Hamartomatous rectal polyps Renal cysts Nonrenal hamartomas Bone cysts Retinal achromic patch Cerebral white matter “migration tracts”

What treatment is out there for TSC? Unfortunately there is no cure. Treatment is provided on a symptom basis. Seizures can be controlled with antiepileptics, surgery may be considered for dermatologic lesions, special needs and developmental delay schooling.

Newer: Recent study of Rapamycin (block mTOR activity) in animal models and preliminary clinical trials shows promising outcome.

If my child has TSC, what is their prognosis? Prognosis in this disease depends on severity of symptoms. The most mild cases have great prognosis whereas the most severe cases have profound disability. MOST can expect normal life expectancy with medical care.

Leading causes of death

Renal disease, brain tumor, lung involvement, status epilepticus

Where did I find this information? Information compiled from UpToDate and the National Institute of Health websites.

Retinal astrocytic hamartomas

Cortical Tuber- TSC