Tuberous sclerosis complex

What it is

Tuberous sclerosis complex is a genetic condition of autosomal dominant inheritance, caused by mutation of the TSC1 gene on chromosome 9 or the TSC2 gene on chromosome 16. It is one of the neurocutaneous syndromes, a group that exists because the nervous system and the skin have a common ectodermal origin, so an embryological disruption causes syndromes involving abnormalities to both systems. Like neurofibromatosis, the majority of features seen in tuberous sclerosis are neurocutaneous, but skin and brain are not the whole picture: hamartomas and tumors also grow in the heart, the kidney, the retina and the lung.

How it presents

The skin carries the signs that reach the clinic first.

• Adenoma sebaceum, that is facial angiofibromas: numerous pink papules on the face in a butterfly distribution over the nose. They are reddish-brown firm papules of 1-2 mm over the nose and cheeks that can extend up to the lower eyelids, and because they look like acne they are treated as acne, with over-the-counter benzoyl peroxide, without relief.
• Ash-leaf spots, three or more: depigmented hypomelanotic polygonal macules over the trunk, which fluoresce under UV light.
• Shagreen patch: a roughened, cobblestone plaque of skin over the lumbosacral area or lumbar spine, a connective tissue nevus.
• Periungual or subungual fibromas: a firm papule or nodule from under the nail bed.
• Cafe au lait spots may be seen.

Neurological manifestations range from epilepsy, which may be infantile spasms or partial, and severe intellectual disability, to mild intellectual disability without seizure. Developmental delay is part of the picture, and the most common neurological complication is infantile spasm.