Tuberous Sclerosis

Tuberous Sclerosis Complex (TSC)

Tuberous Sclerosis Complex (TSC) is an autosomal dominant disorder characterized by hamartomas in many organs, especially the brain, eyes, skin, kidneys, and heart.

• Incidence: 1 in 10,000 births.
• Inheritance: 2/3 of cases are sporadic (new mutations).

Clinical Manifestations

TSC is extremely heterogeneous with variable expression (from normal intelligence to severe intellectual disability/autism).

1. Neurological Features

• Infantile Spasms: TSC is one of the most common causes; often the most common presenting feature in infants. (Best treated with Vigabatrin).
• Cortical Tubers: Brain lesions (Cortical dysplasias).
• Subependymal Nodules: Calcified nodules adjacent to lateral ventricles (Hamartomas).
• Subependymal Giant Cell Astrocytoma (SEGA): Can cause obstruction of CSF outflow $\to$ Hydrocephalus.
• Seizures & Intellectual Disability.

Subependymal calcification: Cortical tubers:

2. Dermatological Features

• Hypomelanotic Macules (Ash-leaf spots): Most common cutaneous manifestation. Easiest to visualize under Wood’s lamp. Apparent in infancy.
• Facial Angiofibromas (Adenoma Sebaceum): Small reddish nodules over nose/cheeks in butterfly distribution (sometimes confused with acne).
• Shagreen Patches: Elevated, rough plaques (connective tissue nevus), usually on lumbar/gluteal regions.
• Ungual Fibromas.
• “Confetti” Skin Lesions.

Ash-leaf hypopigmented areas

Angiofibroma (Adenma Cabeceum)

Shagreen batch

3. Ocular Features

• Retinal Hamartomas (Phakomata): White depigmented patches.
• Retinal achromic patch.

Phakomata of the retina

4. Cardiac Features

• Cardiac Rhabdomyomas: Largest during prenatal life/infancy; rarely symptomatic but may cause arrhythmias. Most common cardiac defect.

5. Renal & Pulmonary Features

• Renal Angiomyolipomas: Most common renal lesion. May undergo malignant transformation; most common cause of death in adults with TSC.
• Multiple Renal Cysts.
• Lymphangioleiomyomatosis (LAM): Interstitial pulmonary disease affecting adults.

Diagnostic Criteria

Definite TSC: 2 Major features OR 1 Major + 2 Minor features. Possible TSC: 1 Major feature OR ≥ 2 Minor features.

Major Clinical Features:

1. Hypomelanotic (Ash leaf) spots (≥ 3, > 5 mm)
2. Angiofibromas (≥ 3) or fibrous cephalic plaque
3. Ungual fibromas (≥ 2)
4. Shagreen patch (connective tissue nevus)
5. Multiple retinal hamartomas
6. Cortical dysplasias (cortical tubers)
7. Subependymal nodules
8. Subependymal giant cell astrocytoma (SEGA)
9. Cardiac rhabdomyoma
10. Lymphangioleiomyomatosis (LAM)*
11. Angiomyolipomas (≥ 2)*

Minor Clinical Features: 12. “Confetti” skin lesions 13. Dental enamel pits (≥ 3) 14. Intraoral fibromas (≥ 2) 15. Retinal achromic patch 16. Multiple renal cysts 17. Nonrenal hamartomas

Diagnosis & Management

Diagnosis: Based on characteristic lesions, seizures, intellectual deficit, and visceral tumors. Neuroimaging (MRI) demonstrates subependymal-calcified nodules.

Management:

• No specific cure; treatment is symptomatic.
• Multidisciplinary team and close follow-up.
• Seizure Control: Infantile spasms best treated with Vigabatrin.
• FDA Approved Tx: Everolimus.
• Genetic counseling.

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