Molecular screening strategies for NF1-like syndromes with café-au-lait macules (Review)

Abstract

Multiple caféaulait macules (CALM) are usually associated with neurofibromatosis type 1 (NF1), one of the most common hereditary disorders. However, a group of genetic disorders presenting with CALM have mutations that are involved in human skin pigmentation regulation signaling pathways, including KIT ligand/KIT protooncogene receptor tyrosine kinase and Ras/mitogenactivated protein kinase. These disorders, which include Legius syndrome, Noonan syndrome with multiple lentigines or LEOPARD syndrome, and familial progressive hyperpigmentation) are difficult to distinguish from NF1 at early stages, using skin appearance alone. Furthermore, certain syndromes are clinically overlapping and molecular testing is a vital diagnostic method. The present review aims to provide an overview of these 'NF1 like' inherited diseases and recommend a cost effective strategy for making a clear diagnosis among these diseases with an ambiguous borderline.