Subcellular defects of hypomelanosis in tuberous sclerosis (TS) (28 subjects) were compared by light and electron microscopy with other forms of congenital circumscribed hypomelanosis that occur in nevus depigmentosus (ND) (8 subjects) and in piebaldism (PB) (4 subjects), respectively.

On the light microscopic level in both TS and ND, the population density of functioning melanocytes was normal but each perikaryon was small, and dopa activity was decreased. On the ultrastructural level, the hypomelanotic skin and hair of TS were associated with a decrease in the synthesis, melanization, and size of melanosomes; the decrease in the size of melanosomes resulted in the aggregation of melanosomes (i.e., a melanosome complex) in the keratinocytes in all the specimens examined. In ND, there were no obvious changes in the size and melanization of melanosomes. There was, however, an aggregation of melanosomes within the melanocytes. The hypomelanosis of ND is related to the decreased synthesis and also, perhaps, abnormal transfer of melanosomes. In PB, the hypomelanosis of the skin and hair results from the absence of functional melanocytes. The hypermelanotic areas of PB, however, characteristically contain melanocytes that synthesize abnormal (spherical and granular) as well as normal (ellipsoidal and lamellar) melanosomes.