Tuberous sclerosis

What is tuberous sclerosis?

Tuberous sclerosis or tuberous sclerosis complex is a genetic disorder that is characterised by hamartomas in many organs, but particularly the skin, brain, eye, kidney and heart. Hamartomas are non-cancerous malformations composed of overgrowth of the cells and tissues that normally occur in the affected area and include naevi (birthmarks). It is also known as epiloia.

Skin lesions, epileptic seizures and developmental delay/behavioural problems are the main features of tuberous sclerosis complex. However, individuals with the condition may be affected in many different ways and with differing degrees of severity. Some patients may have very few or no symptoms at all, whilst others may be severely affected with a multitude of symptoms.

What causes tuberous sclerosis and who gets it?

Tuberous sclerosis is a genetic disorder. About one third of all cases of tuberous sclerosis are inherited from an affected parent. All other cases are due to sporadic new mutations of the tuberin protein gene occurring in the early stages of life.

People of all races and sex may be affected. The condition may become apparent any time from infancy to adulthood but usually occurs between 2-6 years of age.

What are the skin signs of tuberous sclerosis complex?

Skin lesions are found in 60-70% of cases of tuberous sclerosis.

Lesion	Features
Angiofibromas	Facial rash that appears as a spread of small pink or red spots across the cheeks and nose in a butterfly distribution Usually appear between 3-10 years of age and increase in size and number until adolescence Also found around the nails, scalp and forehead Previously incorrectly called adenoma sebaceum
Angiofibromas
Ungual fibromas	Smooth, firm, flesh-coloured lumps that emerge from the nail folds Periungual sites (around the nail) are more common than subungual sites (under the nail) More common on feet than hands Longitudinal groove in the nail may occur without visible fibroma Short red (splinter haemorrhages) or white streaks (leukonychia) may be seen on affected nails
© Dr Ph Abimelec – dermatologue Periungual fibromas
Shagreen patch	Flesh coloured orange-peel connective tissue naevi of varying sizes, usually on the lower back
Shagreen patches
Ovoid or ash leaf-shaped white macules	May be present at birth or early infancy 3 or more white spots at birth suggests diagnosis of tuberous sclerosis
Ash leaf marks

More images of tuberous sclerosis ...

Other organ involvement

Epilepsy is present in about 70% of patients with tuberous sclerosis.

• Usually begins in infancy or early childhood and may precede appearance of skin lesions by years
• The greater the number of tumours (cortical tubers) in the brain, the greater the severity of seizures.

Developmental delay and behavioural problems may also occur. Symptoms include mild to severe mental retardation, autism, attention deficit disorder (ADD), anxiety, depression, paranoia and schizophrenia.

Other signs and symptoms of tuberous sclerosis include:

• Eye involvement: white spots on the iris and white lumps on the retina
• Heart, gastrointestinal and kidney tumours
• Lung changes

What treatment is available?

tuberous sclerosis is a multisystem disorder so treatment from a team of specialist doctors is usually necessary.

Skin lesions, particularly facial angiofibromas, may be psychologically distressing for some patients. Laser treatment or electrosurgery can be used to remove angiofibromas.

Experimentally, the topical mTOR inhibitors rapamycin and sirolimus have proved helpful in reducing angiofibromas in pilot studies involving a few patients. It appears to work best in younger children.