Tuberous sclerosis is an autosomal dominant disorder of variable expression, characterised by extra tissue growths, hamartomas, in almost any organ of the body. Hamartomas include cortical tubers and subependymal nodules in the brain, retinal phakomas, renal cysts and angiomyolipomas, cardiac rhabdomyomas, pulmonary cysts and a variety of cutaneous stigmata - hypomelanic macules, facial angiofibroma, ungual fibroma, shagreen patches and forehead plaques. It is associated with learning disability (in up to 50% of cases), epilepsy (60-70%) and autistic traits (50%). Up to 90% will have some skin signs, and in some cases these will be the only clinical feature of the condition. The condition affects between 1-in-6,500 to 1-in-10,000 people.
Tuberous sclerosis is caused by a defect in cell growth regulating genes, either on chromosome 9 or on chromosome 16. Although approximately two thirds of cases are sporadic, it is essential that genetic counselling is offered to families after diagnosis because of the variability of the disorder. A diagnosis is presently confirmed by clinical and radiological investigations. DNA tests, including pre-natal testing, are now possible for about 85% families.
Tuberous sclerosis can present at any age, with symptoms ranging from seizures or cardiac arrhythmias in infancy, to the later appearance of facial angiofibromas or renal angiomyolipomas. Ensuing investigations may subsequently reveal hypomelanic macules (90%), which fluoresce under ultra-violet light, calcified subependymal nodules (80%), which show up on a CT brain scan, and, in neonates, cardiac rhabdomyomas (60%). Life expectancy is generally good, even for those with severe learning disability. Infrequently, death can occur from brain tumours or kidney disease, but most people have good long-term prospects if monitored appropriately for signs of serious problems.
Skin signs which present from birth onwards are hypomelanic macules (90%), which can repigment in adult life, and smooth, fibrous forehead plaques (25%). Shagreen patches (40%), thickened discoloured skin or nodular lesions, are more likely to develop later in the lower lumbar area. Facial angiofibromas (85%) can appear at any age from two years upwards, starting as tiny red dots and developing during adolescence across the nose, upper cheeks, and particularly in the chin and nasolabial folds. This rash used to be misleadingly called adenoma sebaceum.
Ungual fibromas (50%) can grow from the nails of both hands and feet, from late adolescence onwards causing grooves in the nails even if the lesion cannot be seen. Skin tags occur in 30% of people affected by the condition, and can be profuse at the back of the neck, across the shoulders, in the groin or on the testes.
Since there is no cure for tuberous sclerosis, treatment has to be symptomatic. Epilepsy is treated with drugs (or occasionally surgery); raised intracranial pressure can usually be treated by surgical removal of the tumour and/or the insertion of a shunt; renal problems may require embolisation of an angiomyolipoma or more rarely partial nephrectomy, dialysis or transplantation; symptomatic lung disease may respond to treatment with progesterone; and cardiac problems only rarely require medical treatment. Behavioural difficulties (including hyperactivity, autistic features, sleeping problems and hallucinations) are often the most troublesome for families and frequently require appropriate intervention.
Of the various skin manifestations associated with tuberous sclerosis, there are three which may benefit from treatment. The forehead fibrous plaques and similar growths on the head can sometimes enlarge considerably in late adolescence and require plastic surgery. The ungual fibromas can be removed either by laser or diathermy (although they usually regrow whatever treatment is used). However it is the facial angiofibroma which cause the most psychological distress to patients and these can also bleed profusely if rubbed. These angiofibromas benefit most from the laser treatments, which are currently thought to be the most effective and least traumatic treatments. The argon and pulsed dye lasers have more success on the vascular lesions, whilst the carbon dioxide laser is more successful where there is a greater fibrous component to the lesions.
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