Gianluca Tadini - Multidisciplinary Approach to Neurofibromatosis Type 1

This Springer imprint is published by the registered company Springer Nature Switzerland AG

The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

This textbook represents a highly up-to-date resource for clinicians on the clinical aspects of neurofibromatosis type 1 (NF1). Virtually every clinician in any field of practice will at some time in his/her career be faced with the challenge of a patient with NF1. Many in certain specialties such as paediatrics and paediatric oncology will see many often as the first person to diagnose the condition in a given individual. For those for whom diagnosis and recommendations for management is their bread and butter such as clinical geneticists, this is a really useful handbook. As one of the more frequent rare disorders with a birth incidence reaching the very top end of the definition of rare (1 in 2000), a comprehensive book like this one is a great resource. It is written for clinicians by clinical and laboratory experts and contains an up-to-date review of the new revised diagnostic criteria as well as covering the manifestations across protean organ systems. Chapters range from specific chapters on ocular, bone and cancer manifestations to recommendations for management and surveillance. For those who want to delve further into the molecular mechanism of the disease, there are chapters on molecular diagnostics, the genomics of tumours and involvement of the RAS-MAPK pathway and genotypephenotype correlations. Importantly, this book contains the rationale and process behind the recent changes to the diagnostic criteria. For a condition that until recently had no effective medical treatments, this book contains important up-to-date information on treatment with MEK inhibitors. An insight into the problems with learning and behaviour including the recently described autistic spectrum disorder within NF1 is well covered. Overall I would strongly recommend this book for those who have even slightly more than a passing acquaintance with NF1.

Few textbooks are devoted to a single rare disease. This textbook is an example of a comprehensive compilation of clinical aspects of neurofibromatosis type 1 (NF1), one of the more frequent rare disorders. It is written for clinicians by clinical experts. Several other textbooks deal with the larger group of neurofibromatoses, including neurofibromatosis type 1, neurofibromatosis type 2 (NF2) and schwannomatosis. It is obvious now that NF1 is very different from NF2 and schwannomatosis. NF1 can be easily distinguished clinically from NF2 and schwannomatosis. The two latter conditions are characterized by schwannomas and not by neurofibromas. This distinction will be reflected in an adaptation of the diagnostic criteria for this group of disorders. Conversely, a clear distinction between (mosaic) NF2 and schwannomatosis is frequently not possible without an extensive molecular diagnostic investigation, including molecular analysis of tumour tissue. Clinical examination in children without a family history of NF1 does not always allow to differentiate NF1 from other syndromes characterized by multiple caf-au-lait spots such as Legius syndrome and constitutive mismatch repair syndrome. In this book, specific attention is given to the diagnostic algorithm in children with multiple caf-au-lait macules, the limitations of the NIH diagnostic criteria and the importance of a correct molecular diagnosis.

NF1 is a genetic disorder that can affect many different organ systems both in children and adults, also influencing learning and behaviour. Scientific progress in many different disciplines has changed the care for individuals with NF1 substantially over the past years. Virtually every clinician will be confronted with patients (suspected of) having neurofibromatosis type 1. The book is quite unique in its kind because it covers clinical aspects of the different organ and body systems potentially affected in children and adults with NF1. It is illustrated with beautiful images of most clinical presentations and complications of the disease. NF1 is an autosomal dominant disease and the genetic, molecular diagnostic and reproductive aspects relevant for the clinician are well covered. The chapter on molecular diagnosis is also dealing with specific NF1 mutations that are associated with a higher risk for certain complications. This emerging genotypephenotype correlation can be of value for the personalized medical follow-up in an increasing number of NF1 individuals. Molecular diagnosis of mosaic NF1 poses specific challenges for the diagnostic lab because it is not straightforward to obtain affected cells from biopsies for a proper molecular diagnosis. Nevertheless, it might be important to provide a patient with a mosaic presentation of NF1 with the proper reproductive options. The diagnosis and treatment of nervous system and non-nervous system tumours are reported for both benign and malignant tumours. The book integrates the monitoring, diagnosis and potential treatments of NF1-related phenotypes. The NF1 gene is a tumour suppressor gene but many non-tumoral phenotypes can be present in NF1 individuals and these are covered in specific chapters dealing with potential skeletal, pigmentation, learning and behavioural problems.

Recent literature has shed light on the natural history of NF1 in children and adults. Research on tissues from NF1 patients and in animal model systems has unravelled many of the biological mechanisms underlying complications of the disease. We are better in recognizing individuals at high risk for specific complications. We have learned how to monitor for a specific complication and when to treat or not to treat. The increased knowledge on the importance of aberrant RAS-MAPK pathway signalling for neurofibroma development resulted for the first time in significant targeted treatments for plexiform neurofibromas using MEK inhibitors, some of which are being introduced in clinical practice at the moment. There is no doubt that we will witness an increasing number of new therapeutic approaches in the near future. A specific chapter on therapeutic approaches in NF1 was a high priority.