Autosomal dominant; often sporadic.

2 recognized genes: chromosomes 9 (TSC1: hamartin), 16 (TSC2: tuberin); both tumor suppressor genes.

Incidence 1:10,000. Prevalence 1:10,000 to 1:170,000.

Cardinal features: skin lesions, seizures, mental retardation.

Cutaneous: (a) depigmented or hypomelanotic macules (ash-leaf spots), sometimes need examination with Wood lamp; congenital; (b) facial adenoma sebaceum (facial angiofibroma) in butterfly distribution on nose, cheeks, by age 4 in most children; (c) shagreen patch (rough, elevated plaque) after age 10; usually lumbosacral; (d) fingernail or toenail (ungual) fibromas, (e) café-au-lait spots.

Neurologic: (a) seizures: myoclonic spasms, hypsarrhythmia in infants; generalized tonic-clonic or partial complex seizures later; (b) mental retardation (in correlation with refractory seizures), (c) autism.

Ophthalmic: hamartomas of retina or optic nerve (50% of patients); multinodular near disc (mulberry appearance); flat, circular at periphery.