Tuberous Sclerosis

Clinical Features, Genes and Therapeutics

Clinical features of tuberous sclerosis

Tuberous sclerosis (also known as Bourneville Disease) is an autosomal dominant condition Opens in new window characterized by hamartomas of the skin, eye, brain, heart, kidney, and other organs. There is mental retardation Opens in new window, epilepsy and cutaneous abnormalities.

The skin signs include adenoma sebaceum (reddish papules around the nose, periungual fibroma (nodules arising from the nail bed), shagreen patches (flesh-colored plaques on the trunk), ash-leaf hypopigmentation and café-au-lait patches Opens in new window. There may be pitting of dental enamel.

Most cases of tuberous sclerosis is due to a mutation in either the TSCI gene (that encodes hamartin) or the TSC2 gene (that encodes tuberin). Skin changes and epilepsy usually develop before the age of 5.

The epilepsy is usually focal in nature and occurs in about 80% of patients. Severe mental retardation is found in about one-half of patients and may be progressive.

Less common features include rhabdomyomas of the heart; angiomyolipmas of the kidney; renal cysts or renal cell carcinoma; hamartomatous colonic polyps with malignant potential; cystlike lesions and irregular thickening of the bony corte; dyspnea; spontaneous pneumothorax; and localized giantism.

Skin Features

About 70% of patients have skin involvement, and many of the lesions are almost pathognomonic when accompanied by epilepsy. They include the following:

  • Ash-leaf-shaped white macules occur in a dermatomal distribution on the trunk or extremities.
  • Facial angiofibromas (adenoma sebaceum) characteristically develop during early childhood and appear as firm, discrete, red/brown, telangiectatic papules.
  • A shagreen patch or collagenoma appearing as an irregularly thickened, soft, skin-colored plaque in the lumbosacral area, forehead, or eyelids.
  • Subungual and periungual fibromas.
  • Other skin lesions, such as soft, pedunculated fibromas around the neck and axillae, and diffuse cutaneous reticula.
  • Fibromas of the gums, palate, tongue, larynx, or pharynx.

Ocular Featurs

The ocular features include the following:

  • Poliosis and a shagreen patch of the lid.
  • Pedunculated white or gray conjunctival tumors.
  • Opacities of the cornea and lens.
  • Hypopigmented lesions of the iris and choroid.
  • Single or multiple, unilateral or bilateral astrocytic retinal hamartomas usually occur in the posterior pole, are slow growing, and have a mulberry appearance. They eventually calcify, giving a glistening or cottage cheese appearance.
  • A second form of retinal hamartomas is flat, smooth-appearing, and semitranslucent with poorly defined boundaries. These lesions are more common but usually are missed because their presence is not considered.
  • Keratoconus, strabismus, nystagmus, visual field loss, tilted discs, myelinated nerve fibers, depigmented areas of retinal pigment epithelium, peripapillary veils, optic astrophy, papilledema, and ocular colobomas have been reported.


Vogt’s triad of facial angiofibromas, seizure disoreder, and mental retardation is virtually diagnostic. CT scan of the brain will help assess ventricular deformity and locate tumor deposits.

MRI can be useful to locate subependymal nodules. Electroencephalogram and renal ultrasound are used to screen for associated conditions of tuberous sclerosis. The diagnosis in children may be difficult or impossible if one or two white macules are the only finding. More than five shagreen patches are highly suggestive of tuberous sclerosis


Therapy is centered on providing symptomatic relief. Anticonvulsants are used for seizures, shunting for hydrocephalus, and behavioral and educational strategies for mental retardation.

Laser surgery can be useful to treat the angiofibromas. Genetic counseling should be offered to patients diagnosed with tuberous sclerosis due to the heritable nature of this disease.

See also:
  1. de Vries, P. J. (2010a). Neurodevelopmental, psychiatric and cognitive aspects of tuberous sclerosis complex. In D. J. Kwiatkowski, V. H. Whittemore, & E. A. Thiele (eds.). Tuberous Sclerosis Complex: Genes, Clinical Features, and Therapeutics. Weinheim, Germany: Wiley-Blackwell, 229-267.
  2. de Vries, P. J., Hunt, A., & Bolton P. F. (2007). The psychopathologies of children and adolescents with tuberous sclerosis complex (TSC): a postal survey of UK families. European Child and Adolescent Psychiatry, 16, 16-24.
  3. Franz, D. N., de Vries P. J., & Crino P. B. (2009). Giant cell astrocytomas in tuberous sclerosis complex. Archives of Diseases in Childhood, 94, 75-76.
  4. Franz, D. N., Leonard, J., Tudor, C., Chuck, G., Care, M., Sethuraman, G., et al. (2006). Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Annals of Neurology, 59, 490-498.
  5. Davies, D. M., Johnson, S. R., Tattersfield, A. E., et al. (2008). Sirolimus therapy in tuberous sclerosis or sporadic lymphangioleiomyomatosis. New England Journal of Medicine, 358, 200-203.