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Molecular Diagnosis for NF1

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Multidisciplinary Approach to Neurofibromatosis Type 1

Abstract

Comprehensive molecular testing approaches developed over the last 2 decades detect a pathogenic variant in ~90–95% of non-founder patients with classic NF1 features (including pigmentary signs and neurofibromas). The mutational spectrum is complex and guidelines and databases have been developed, and will need continued improvement, to assist with interpretation of the variants.

Limited genetic heterogeneity has been recognized as some patients with a milder presentation of pigmentary features without neurogenic tumors have Legius syndrome, due to SPRED1 variants.

Molecular diagnosis allowed recognizing that some sporadic patients have mosaic or segmental NF1 due to a somatic NF1 pathogenic variant originating, and clonally expanding, after fertilization. The phenotype in these patients depends on the timing and types of progenitor cells affected.

Furthermore, several specific recurrent pathogenic NF1 variants have been identified that are associated with a clinically relevant genotype-phenotype association, predisposing to either a much milder or more severe phenotype. Although the clinical course remains largely unpredictable for the majority of patients, almost 10% of the NF1 population carries a variant that now allows a more precise forecasting of the symptoms more likely (not) to occur.

These recent advances are discussed in this chapter.

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Authors and Affiliations

  1. Department of Genetics at UAB, Medical Genomics Laboratory, Birmingham, AL, USA

    Ludwine M. Messiaen

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  1. Ludwine M. Messiaen
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Correspondence to Ludwine M. Messiaen .

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Editors and Affiliations

  1. Center for Inherited Cutaneous Diseases, University of Milan, Milan, Milano, Italy

    Gianluca Tadini

  2. Center for Human Genetics, Universitaire Ziekenhuizen Leuven Center for Human Genetics, Leuven, Oost-Vlaanderen, Belgium

    Eric Legius

  3. Department of Human Genetics, KU Leuven, Leuven, Belgium

    Hilde Brems

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Messiaen, L.M. (2020). Molecular Diagnosis for NF1. In: Tadini, G., Legius, E., Brems, H. (eds) Multidisciplinary Approach to Neurofibromatosis Type 1. Springer, Cham. https://doi.org/10.1007/978-3-319-92450-2_3

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  • DOI: https://doi.org/10.1007/978-3-319-92450-2_3

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