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This monograph includes five chapters about neurofibromatosis type 1 (NF1), a condition characterized by changes in skin coloring and the growth of tumors along nerves in the skin, brain, and other parts of the body. Chapter One concerns the evolving molecular biology, targeted therapeutics, and neurocognitive deficits in neurofibromatosis type one. Chapter Two focuses on gastrointestinal stromal tumors and reviews the clinicopathologic features of these tumors and discusses differential diagnostic considerations. Chapter Three explores juvenile myelomonocytic leukemia, a rare hematological malignancy of the pediatric population, and its association with NF1 and distinguishing features in this context. Chapter Four reviews molecular approaches for the diagnosis of NF1, from single-gene testing to next-generation sequencing of gene panels, with a focus on the issues of sensitivity and variant interpretations. Finally, Chapter Five focuses attention on focal cortical dysplasia that has been identified in the population of NF1 patients that have had coexistent hippocampal sclerosis.

This volume offers an update of the clinical signs, diagnostic criteria (including molecular diagnosis) and targeted therapies for a particular type of genodermatosis, providing a handy and unique tool for early diagnosis. In recent years, our understanding of genodermatosis and neurocutaneous syndromes has increased, but although Type 1 Neurofibromatosis (NF1) is the most common neuroectodermal disorder and involves a large number of patients and medical disciplines, this syndrome remains underestimated, often misdiagnosed thus leading to inaccurate treatment. The literature on the molecular and pathogenetic aspects is ample, but current clinical approaches, classification, diagnostic criteria and treatment protocols are outdated, creating difficulties in early diagnosis and treatment. As such, a chapter is devoted renewing current diagnostic criteria; it includes clinical and molecular data, to offer a sound, updated discussion basis for a consensus conference.NF1 is a “time-dependent” disorder, meaning that the onset of clinical signs are closely linked to patient age and the book discusses this particularly neglected aspect extensively, as well as the latest molecular diagnosis techniques, which are highly sensitive have not been included in the diagnostic criteria. It also explains the role of the RAS-MAPK pathway and genotype-phenotype correlations. In addition it explores new concepts concerning the pathogenesis of neurofibromas and other hamarthomas and their relevance for a modern therapeutical approach with targeted molecular drugs, as well as newly discovered aspects of NF1 in all internal organs, together with their diagnostic counterparts. A chapter on mosaic neurofibromatosis is also included. There is a particular focus on differential diagnosis (i.e. other diseases with café-au-lait macules), and the recently described Legius syndrome will be presented directly by Prof Eric Legius. All chapters are easy-to-understand, up-to-date, comprehensive and concise tools and are intended for a wide range of professionals involved with genetic disorders of the skin and neurocutaneous diseases: dermatologists, pediatricians, neurologists, oncologists and general practitioners.

The neurofibromatoses are autosomal-dominant genetic disorders of the nervous system that primarily affect the development and growth of neural cell tissue. These disorders cause tumors to grow on nerves and produce other abnormalities such as skin changes and bone deformities. In recent years, the genes and mutations causing neurofibromatoses have been identified. The main types of neurofibromatoses, type 1 (NF1) and type 2 (NF2), have been shown to be distinctive disorders both clinically and genetically. More recently, allelic and non-allelic subtypes of NF1 have been defined as well as the NF2-related condition schwannomatosis. Many of the complex molecular mechanisms leading to the neurofibromatoses have been elucidated, resulting in a growing body of publications which are difficult to keep up with. This volume provides an important overview of recent findings on the neurofibromatoses. It focuses on the genetics and molecular biology underlying these diseases, but also covers their clinical features, diagnosis and treatment, stressing the need for interdisciplinary medical care. With contributions by the foremost investigators in the field, this timely book will appeal to geneticists, genetic counselors, pediatricians, neurologists and oncologists.