Tuberous Sclerosis

Question 1

What is the inheritence pattern of tuberous sclerosis?

Answer 1

AD

Question 2

What is the genetic defect in tuberous sclerosis?

Answer 2

TSC1 (protein product hamartin) at chromosome 9q34.3

TSC2 (protein product tuberin) at chromosome 16p13.3

Question 3

What are the associated medical findings with tuberous sclerosis?

Answer 3

1. Cortical brain tubers
o Seizures
2. Subependymal nodules --> astrocytomas
3. Dermatologic:
a) Ash leaf spots
b) angiofibromas
c) Shagreen patches
d) Ungual fibromas
4. Retinal astrocytic hamartomas
5. Cardiac rhabdomyosarcomas
o Most resolve spontaneously

Question 4

What are the developmental outcomes for tuberous sclerosis?

Answer 4

1. Intellectual Disability (45-75%)
2. Autism (50%)
3. Learning disabilities
   a) Memory impairment
   b) Dyscalculia
   c) Visuospatial distrubances
   d) Dyspraxia

Question 5

What is the DDx for tuberous sclerosis?

Answer 5

1. Vitiligo
2. Pityriasis alba
3. Cutaneous allergy to nickel jewelry
4. Acne (facial angiofibromas of TS)

Question 6

What are the recommendations for tuberous sclerosis?

Answer 6

1. CT/MRI at diagnosis
2. Echocardiogram in infancy
3. Renal US at diagnosis
4. Peds Ophthalmology at diagnosis
5. Early Developmental Evaluation

Question 7

What are the major clinical manifestations for Tuberous Sclerosis?

Answer 7

1. Skin lesions: ash leaf spots, facial angiofibroma, shagreen patches, ungual fibromas
2. Brain lesions (cortical tubers, subependymal nodules, seizures)
3. Kidney lesions (angiomyolipomas, cysts)
4. Heart lesions (rhabdomyomas)

Question 8

What are the diagnostic criteria for Tuberous sclerosis?

Answer 8

2 major OR 1 major and >2 minor features.

Genetic TSC1 or TSC2
Major Criteria:
• >3 angiofibromas
• >2 ungual fibromas
• >3 hypomelanotic macules (@least 5mm in diameter)
• shagreen patch
• cortical dysplasias
• subependymal nodules
• multiple retinal hamartomas
• cardiac rhabdomyoma
• lymphangioleiomyomatosis (LAM)
• >2 angiomyolipomas 

Minor Criteria:
• >3 dental enamel pits
• >2 intra-oral fibromas
• non-renal hamartomas
• retinal achromic patch
• "confetti" skin lesions
• multiple renal cysts