HISTORY OF THE TUBEROUS SCLEROSIS COMPLEX

How the concept of the tuberous sclerosis complex (TSC) has developed over a period of time spanning 160 years has come form simple clinical observations, pathological studies and technological advances of imag ing methods, It all began with PFO Rayer's color plate of a drawing of a patient who apparently had facial angiofibroma, published in the ye ar 1835, and continued with von Recklinghausen's report of cardiac myo mas and cerebral sclerosis in a newborn who had died minutes after bir th. The seminal contribution was provided by D.M. Bourneville who, in 1880, reported and named as tuberous sclerosis the neuropathological f indings in a young patient with seizures, hemiplegia, and mental subno rmality who also had renal tumors, We now know that TSC is a hamartoma tosis, and thanks to studies of recent years using positional cloning and DNA analysis, we are beginning to understand the biological mechan isms of these disorders which include NF1, NF2 and von Hippel-Lindau d isease, Unique to TSC is that it is both phenotypically and genotypica lly heterogeneous, One of two suspected genes found in chromosome 16 b y positional cloning has been cloned (TSC2), Another one that was disc overed earlier in chromosome 9 (TSC1) has not yet been characterized, The gene product from TSC2 has been named tuberin.