The phakomatoses

The “phakomatosis” concept was formulated early in the twentieth century by the ophthalmologist van der Hoeve [Trans Opthalmol Soc U K. 1932;52:380-401]. He included 3 disorders in the group-neurofibromatosis, tuberous sclerosis complex, and von Hippel-Lindau syndrome-on the basis of the occurrence of patchy ophthalmologic manifestations in each disorder. Since the name was coined, much has been learned about the pathogenesis of these 3 disorders [J Natl Cancer Inst. 2000;92:530-533]. It is clear that 2 of them-neurofibromatosis and tuberous sclerosis-are collective terms for multiple disorders. Each of the conditions is caused by distinct genetic defects, with little commonality in terms of protein function. Yet, in some respects, the disorders share a pathogenetic mechanism, that of the tumor suppressor gene [J Natl Cancer Inst. 2000;92:530-533]. This review will briefly describe these disorders in light of what has been learned about underlying molecular pathogenesis. In each case, genetic testing is beginning to be available; principles of the use of genetic tests will be described.