Tuberous sclerosis

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Tuberous Sclerosis (TS) is one of the Neurocutaneous Syndromes (also known as 'Neuroectodermal Syndromes'). It is a genetic disorder of cellular differentiation and proliferation.

  • It is of variable severity and may not present until later in childhood.
  • Characterised by hamartomas in the brain, skin and other organs

Tuberous Sclerosis Complex is now largely used due to the wide variation in clinical manifestation.

  • First described by Von Recklinghausen in 1862.
  • Bourneville first used the term 'Tuberous Sclerosis' and Sherlock first used 'Epiloia' to describe the triad of epilepsy, low intelligence and adenoma sebaceum.


~ 1 in 10 000

  • No sexual or race predilection.

Clinical features

Not all have to present to make the diagnosis (see below)

  • Most children are diagnosed between the 2-6 years old.

Main Features

  1. Learning impairment (often severe)
    1. 50% have normal intelligence
  2. Epilepsy
  3. Skin lesions

May present with Infantile Spasms.

Skin Signs

  • Adenoma Sebaceum - Angiofibromas (red nodules) develop on the cheeks and across the nasal bridge during childhood
  • Shagreen patches -firm plaque on trunk
  • Periungal fibromas - nodules arising from nail bed
  • Ash-leaf macule - pale, leaf-shaped, best seen under a Wood's lamp (ultraviolet)
    • 95% by age 5 years
  • CafĂ© au lait patches
  • Dental enamel pitting
  • Amelanotic naevi

Other Features

Internal hamartomas

  • heart, kidney, lung, retina and CNS
    • Cardiac rhabdomyomas
    • Retinal phakomas (glial masses)
  • Renal
    • tumours / hamartomas
    • cysts / polycystic kidneys
    • hypertension
  • Gliomas
    • Glial overgrowth in brain


Diagnosis requires 2 major or 1 major and 2 minor criteria.

Major Criteria Minor Criteria
Ademona sebaceum Dental enamel pitting
Ungual fibromas Rectal polyps
Shagreen's patches Bone cysts
Cortical tubers Cerebral white matter 'migration tracts'
Subependymal nodules Gingival fibromas
Subependymal giant cell astrocytoma Non-renal hamartoma
Retinal nodular hamartoma Retinal achromic patch
Cardiac rhabdomyomata Multiple renal cysts

Aetiology / Genetics

TS is an autosomal dominant condition due to specific gene mutations:

  • Chromosome 9q: Hamartin gene: TS1
  • Chromosome 16q: Tuberin gene: TS2


Clinical Testing

  • Clinical examination
    • Developmental assessment
  • MRI head
  • Ophthalmological assessment
  • Renal USS
  • ECG
  • EEG where indicated

Genetic Testing

Clinical diagnosis should be established before genetic testing for TS1 and TS2 mutations.

  • Parents of children diagnosed with TS should be carefully examined. Forme frustes exist.
  • As an autosomal genetic condition, counselling should be offered re. implications for future offspring.
  • 60% of TS arise due to new mutations.


Management is symptomatic

  • Epilepsy control
  • Social, emotional and eductional support
  • Genetic counselling re. future offspring.
  • Vigilance for tumours and associated morbidity


Annual assessment of the child and family is recommended as a minimum.


The course of this disease very much depends on the individual manifestation in each patient.

  • 25% of severely affected children may die before 10 years of age and 75% before 25 years.


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