This uncommon condition, with a prevalence of about 1 in 12 000 in children under 10 years, is also inherited as an autosomal dominant trait, with variable expressivity even within the same family. As fertility is reduced, transmission through more than two generations is rare.
Mutations at two different loci can, independently, cause clinically identical tuberous sclerosis. The prod-uct of one gene (TSC1), lying at 9q34, is hamartin; that encoded by the other gene (TSC2) is tuberin. Both are associated in vivo, and probably act in the same biological pathways as tumour suppressors. TSC1 gene mutations are responsible for a minorityof cases and are under-represented in sporadic cases
The skin changes include the following.
• Small oval white patches (‘ash leaf macules’) occurin 80% of those affected. These are important as they may be the only manifestation at birth.
• Adenoma sebaceum occur in 85% of thoseaffected. They develop at puberty as pink or yellowish acne-like papules on the face, often around the nose (Fig. 21.4).
• Peri-ungual fibromas occur in 50% of patients.These develop in adult life as small pink sausage-like lesions emerging from the nail folds (Fig. 21.5).
• Connective tissue naevi (‘shagreen patches’) are seenin 40% of patients. Cobblestone, somewhat yellow plaques often arise in the skin over the base of the spine.
Other features may include:
• epilepsy (in 75% of patients);
• mental retardation (in 50% of patients);
• ocular signs, including retinal phakomas and pig-mentary abnormalities (in 50% of patients);
• gliomas along the lateral walls of the lateral vent-ricles (80% of cases) and calcification of the basal ganglia; and
• renal and heart tumours.
Any baby with unexplained epilepsy should be examined with a Wood’s light to look for ash leaf macules. Skull X-rays and computer assisted tomography scans (Fig. 21.6) help to exclude involve-ment of the central nervous system and kidneys. The lesions of adenoma sebaceum (a misnomer, as histologically they are angiofibromas) may be mis-taken for acne.
Affected families need genetic counselling. Apparently unaffected parents with an affected child will wish to know the chances of further children being affected. Before concluding that an affected child is the result of a new mutation, the parents should be examined with a Wood’s light and by an ophthalmologist to help exclude the possibility of genetic transmission from a subtly affected parent. As the gene defects become established, prenatal screening of DNA should indic-ate those at risk.
Adenoma sebaceum improves cosmetically after electrodessication, dermabrasion or destruction by laser but tends to recur.