Rare diseases: Tuberous sclerosis

Dr Harry Brown explains this rare genetic disorder

What is it?

  • Tuberous sclerosis is an inherited disorder which affects cell growth.
  • It can be autosomal dominant but spontaneous genetic mutations can also happen.
  • It causes hamartomas to appear in multiple organs including the kidneys, brain, heart and skin.
  • Findings and severity of the condition can be variable.
  • Some of the clinical features may only appear when the child is older than one year and so the diagnosis may not be made until the person is much older.

Who is at risk?

  • Tuberous sclerosis does not specifically affect one sex more than another.
  • Two genes have been identified in the pathogenesis of the condition, TSC1 (chromosome 9) and TSC2 (chromosome 16).
  • An abnormality in either gene can result in increased growth in some organs.
  • The TSC1 gene leads to production of hamartin whilst TSC2 leads to tuberin. These two products react with each other to control growth of cells. Genetic mutations lead to excessive tissue growth.

Signs and symptoms

  • Skin lesions affect virtually all patients and their presence helps in diagnosis.
  • Renal lesions occur in a large majority of patients.
  • Sometimes renal failure occurs due to the number of cysts affecting the kidneys.
  • Lesions affecting the nervous system can cause significant clinical problems and may even be fatal.
  • Many people with lesions involving the nervous system have epilepsy; infantile spasms can be a presenting feature.
  • A first fit is common by the age of two years of age.
  • Developmental delay, learning problems and problems of intellect can occur.
  • Some can develop autism.
  • Giant cell astrocytoma and kidney diseases can result in mortality.
  • Hamartomas of the retina occur in around half of affected people and may be seen by fundoscopy.
  • Dermatological manifestations include facial angiofibromas.
  • If transmission of tuberous sclerosis is autosomal dominant then it is very likely that one of the parents will also have skin lesions.
  • Rhabdomyomas of the heart may be observed when born and in fact may be detected on foetal ultrasound in affected unborn babies.

How is it managed?

  • Diagnosis is made by clinical suspicion, imaging of affected organs and genetic testing for mutations in the TSC1 and TSC2 genes.
  • Genetic counselling may be needed for close family members.
  • Treatment is based on symptom control and aimed at controlling the complications caused by the disorder.
  • Epilepsy may require pharmacological intervention.
  • Neurosurgery may be needed to control epilepsy or other intracranial complications.
  • Hypertension secondary to renal pathology may need treatment.
  • Developmental and behavioural issues will need addressing.

Dr Brown is a GP in Leeds

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