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Definitions and Epidemiology

Tuberous sclerosis is a genetic disease occurring in approximately 1 in 10,000 people. It is inherited in an autosomal dominant pattern isolated to chromosome 9, and in rare instances chromosome 16.1,2 Though autosomal dominant, there is variable penetrance.3

Pathogenesis

Tuberous sclerosis is associated with a variety of central nervous system findings. Cortical tubers are the hallmark finding on imaging and pathologic specimens. These consist of giant cells, gliosis, disorganized myelin, and hamartomas. Heterotopic islands of gray matter in the deep white matter are commonly seen.4 Subependymal giant-cell astrocytomas can occur and may result in clinical findings secondary to the associated mass effect.5

Clinical Presentation/Diagnosis

Tuberous sclerosis was initially defined by Voigt's classical triad of epilepsy, adenoma sebaceum, and mental deficiency. Unfortunately, this classic triad is present in only one-third of patients.4

The primary diagnostic criteria for tuberous sclerosis includes adenoma sebaceum, which occur in 90% of patients above 4 years of age. Ungual fibromas typically appear at puberty. Cerebral cortical tubers are an integral component of tuberous sclerosis. Subependymal nodules, also called "candle gutterings," may be seen on imaging studies but may be absent in the very young patient. Fibrous forehead plaques also increase in frequency with increasing age.

There are also a number of secondary criteria for the diagnosis of tuberous sclerosis. Infantile spasms occur in three-quarters of patients and usually start at 4 to 7 months of age. In these patients, the EEG may show hypsarrhythmia.6

Ash leaf spots occur in 90% of patients. They are hypomelanotic lesions and may be the earliest skin manifestation of tuberous sclerosis. These lesions require a Wood lamp for diagnosis (Figure 22-1). Shagreen patches are another dermatologic manifestation of tuberous sclerosis. These lesions are subepidermal fibrous patches that have the appearance of orange peel. While they may occur in various locations, they are most common in the lumbosacral region (Figure 22-2).

Figure 22-1.

Hypomelanotic ash leaf macules on the lower leg of a child with tuberous sclerosis complex. (Reproduced with permission from Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Lefferell DJ. Fitzpatrick's Dermatology in General Medicine. 7th ed. New York: McGraw-Hill; 2008: Figure 141-2.)

Figure 22-2

The Shagreen patch in tuberous sclerosis complex is a firm, bumpy plaque that is usually located on the lower back. (Reproduced with permission from Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Lefferell DJ. Fitzpatrick's Dermatology in General Medicine. 7th ed. New York: McGraw-Hill; 2008: Figure 141-7.)

A number of other physical findings may occur including retinal hamartomas, retinal phakomas, ...

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