Hypothesis: Jadassohn nevus phakomatosis: A paracrinopathy with variable phenotype

Publisher Website
Google Scholar
Abstract
It has been postulated that the phakomatoses are paracrine growth regulation disorders (paracrinopathies). To determine how Jadassohn nevus phakomatosis (JNP) may fit such a pathogenetic model, a phenotype analysis of 13 propositi with JNP and a review of most reported JNP patients were done. The phenotypes of the propositi and the reviewed patients showed a great variability from a solitary congenital epidermal nevus to extensive cutaneous lesions with associated severe noncutaneous anomafies. Review of long‐term observations of JNP patients demonstrated considerable phenotypic changes within and beyond the boundaries of the nevi. The changes included a multitude of postnatal rare benign and/or malignant tumors and unusual manifestations: renal rickets, hepatomegaly, visceral cysts, vasculopathy, and even gangrene. Thus, a life‐long predisposition to dysregulation of paracrine growth factors (GFs, regulatory peptides, peptide regulatory factors, and cytokines), foremost somatomedin‐C (Sm‐C, IGF‐I), epidermal, fibroblast, platelet‐derived GFs, and transforming GF‐β is implied. Laboratory evidence for the presumed GF dysregulation in the phakomatoses came from tissue culture study of patients with neuro‐fibromatosis type 1 (NF‐1). Compared to controls their “normal” skin showed ultrastructural changes of markedly increased number of melanin macroglobuli within the melanocytes. Paracrine GFs as relevant to hamartomatous growth were incriminated by radioimmunoassays of cutaneous neurofibromas showing two‐fold or greater increase of Sm‐C levels compared to the levels in the adjacent skin. Thus, NF‐1 appears to be a paracrinopathy. JNP shows many more dynamic changes throughout the life span of the patients than NF‐1. In the near future paracrinology may aid endocrinology and oncology in treating patients with disorders of these three growth mechanisms in man.

This publication has 46 references indexed in Scilit: