The phakomatoses as paracrine growth disorders (paracinopathies)

A microcomputer database management system retrieved all 170 probands with phakomatoses evaluated through the genetic clinics at the University of South Florida between January 2, 1982 and December 31, 1987. Neurofibromatosis (NF) was the diagnosis of 118 of them; 42 had other phakomatoses and 10 had transitional phenotypes difficult to classify. The analysis of the hamartomas of all probands indicated disorganized differentiation and overgrowth of cell species characteristic for the involved tissue and location. Abundance of extracellular fibrillary components was also evident in most hamartomas. Adequate blood supply was a conditio sine qua non. This was seen in monogenic, sporadic, transitional and combined phakomatoses alike and implied a common pathogenesis. The paracrine growth factors and their regulation emerged as the most plausible common denominator for the pathogenesis. A unitary pathogenetic hypothesis is proposed that the phakomatoses represent paracrine growth regulation disorders (paracrinopathies). Conditions such as fibromatoses, lipomatoses, lipodystrophies, hemihyper/hypotrophies, including Russell-Silver and Beckwith-Wiedemann syndromes may be proven to be paracrinopathies as well.