Tuberous Sclerosis

Tuberous Sclerosis is a multisystem disorder with a highly variable clinical presentation. The high degree of variability has led to the condition now being called tuberous sclerosis complex (TSC).

Epidemiology

• Incidence is ~ 1/10 000
• Male = Female

Clinical presentation

• The most common presentation is in childhood with epilepsy [90%] or developmental delay [80%] or infantile spasms [30%]
• Up to 50% of affected individuals may also have normal intelligence
• Increasing numbers are being diagnosed in adulthood.

Physical signs

• Facial angiofibromas or forehead plaques
• Ungal fibromas
• Hypopigmented macules
• Shagreen patch

Diagnosis

Diagnostic criteria have been developed for TSC which require 2 major features or one major and 2 minor features.

Major clinical diagnostic features

• Developmental delay
• Epilepsy
• Subependymal nodules/ hamartomas /cortical tubers
• Periventricular calcification
• Facial angiofibromas or forehead plaques
• Ungal fibromas
• Hypopigmented macules
• Shagreen patch
• Renal angiomyolipomas
• Cardiac rhabdomyoamas (as neonates) [30-70%]

Minor clinical diagnostic features

• Renal cysts [40%]
• Dental Pits
• Bone cysts
• Rectal polyp hamartomas
• Retinal hamartomas
• Hepatic hamartomas[15%]

Complications

Sporadic mutation patients with TSC1 mutations have a milder condition compared to TSC2 patients. Otherwise there is little difference between the genotypes in their complication rates.

The lesions of TSC are often asymptomatic but the main complications are:

• Intractable seizures
• Severe developmental delay
• Intracranial hypertension secondary to subependymal giant cell astrocytomas
• Enlarging renal angiomyolipomas and haematuria
• Cystic lung disease (lymphangiomyomatosis) in women