In approximately 90 percent of patients with tuberous sclerosis, congenital hypomelanotic macules—“ash-leaf” lesions—formerly mistaken for partial albinism or vitiligo, appear before any of the other skin lesions (Fitzpatrick et al). Gold and Freeman, as well as Fitzpatrick and colleagues, emphasized the frequency of these leukodermic lesions and their value in the diagnosis of tuberous sclerosis during infancy, before the appearance of the other characteristic cutaneous lesions. The hypomelanotic areas are arranged in linear fashion over the trunk or limbs and range in size from a few millimeters to several centimeters; their configuration is oval, with one end round and the other pointed, in the shape of an ash leaf. A Wood’s lamp, which transmits only ultraviolet rays, facilitates the demonstration of the ash-leaf lesions because of the absence of melanoblasts, which normally absorb light in the ultraviolet range (360-nm wavelength). These lesions become pink when rubbed and contain sweat glands; they are not usually present on the face or head. There is occasionally a white tuft of hair (poliosis). Electron microscopic examination of the hypomelanotic lesions shows a normal or reduced number of melanocytes, but their dopa reaction is reduced and melanosomes are small.
The well-developed facial lesions (adenomas of
Pringle), pathognomonic of tuberous sclerosis, are present in 90 percent of patients older than 4 years of age. Although called adenoma sebaceum, these nodules are actually angiofibromas; the sebaceous glands are only passively involved (Fig. 37-5). Typically they are red to pink nodules with a smooth, glistening surface, and they tend to be limited to the nasolabial folds, cheeks, and chin; sometimes they also involve the forehead and scalp. The earliest manifestation of facial angiofibromatosis may be a mild erythema over the cheeks and forehead that is intensified by crying. The occurrence of large plaques of connective tissue on the forehead is usually expressive of a severe form of the disease.
On the trunk, the diagnostic lesion is the “shagreen patch” (in reality a plaque of subepidermal fibrosis) found most often in the lumbosacral region. It appears as a flat, slightly elevated, flesh-colored area of skin 1 to 10 cm in diameter, with a “pigskin,” “elephant hide,” or “orange peel” appearance (Fig. 37-6). Another common site of fibromatous involvement is the nail bed; subungual fibromas usually appear at puberty and continue to develop with age. Other common skin changes, not in themselves diagnostic, include fibroepithelial tags (soft fibromas), café-au-lait spots, and port-wine hemangiomas.
The brain exhibits a number of diagnostic anomalies. Broadening, unnatural whiteness, and firmness of parts of some of the cerebral convolutions are simulated by no other disease. These are the tubers after which the disease is named. On the surface of the brain, they range in width from 5 mm to 2 or 3 cm. Their cut surface reveals a lack of demarcation from cortex and white matter and the presence of white flecks of calcium; these, which are readily seen on CT and MRI, are called brain stones (see below and Fig. 37-7). The walls of the lateral ventricles may be encrusted with white or pink-white masses resembling candle gutterings. When calcified, they appear in radiographs as curvilinear opacities that follow the outline of the ventricle. Rarely, nodules of abnormal tissue are observed in the basal ganglia, thalamus, cerebellum, brainstem, and spinal cord.