Tuberous sclerosis and guttate leukodermas.

Abstract

The clinical, histopathologic, and electron microscopic features of guttate leukodermas are reviewed, including the hypomelanoses of the skin and hair observed in the tuberous sclerosis complex (TSC). The hypopigmentation seen in patients with TSC is related primarily to a decrease in the function of epidermal and follicular melanocytes; the density of active melanocytes is normal. Poorly developed dendritic processes are observed frequently as are melanosomes that are smaller in size and less melanized than those in melanocytes of uninvolved skin and hair. There is also a decreased number of melanosomes within the melanocytes, but in the absence of abnormal autophagic aggregation. These hypofunctioning melanocytes transfer fewer melanosomes to surround keratinocytes, and therefore the overall melanin content in the affected skin and hair is decreased. Two loci for TSC have been clearly identified, and one gene on chromosome 16p 13.3 (TSC-2) has been cloned. The protein product of the TSC-2 gene, tuberin, is involved in the regulation of cellular growth. The second gene is an chromosome 9q34 (TSC-1) near the locus for dopamine-o-hydroxylase, an enzyme involved in the synthesis of catecholamine neurotransmitters. The differential diagnosis of the guttate leukoderma of TSC includes several clinical entities such as idiopathic guttate hypomelanosis, disseminated hypopigmented keratoses, and dyschromic amyloidosis.