NF1 mutations are the underlying cause of neurofibromatosis type 1 (NF1), a neuro-cardio-facio-cutaneous syndrome (NCFC). Because of the clinical overlap between NCFCs, genetic analysis of NF1 is necessary to confirm a clinical diagnosis NF1. This report describes the clinical and genetic findings of 18years of NF1 molecular diagnostics in the Netherlands. A pathogenic mutation was found in 59.3% (1178/1985) of the index patients, mostly de novo (73.8%). The majority of the index patients (64.3%) fulfilled the National Institute of Health NF1 criteria, a pathogenic mutation was found in 80.9% of these patients. Seventy-four percent of the index patients with an NF1 pathogenic mutation and not fulfilling the NF1 criteria is <12years, in agreement with the fact that some NF1 symptoms appear after puberty. Genotype-phenotype correlations were studied for 527 index patients. NF1 patients with a type 1 microdeletion have a sixfold higher risk of special education vs NF1 patients with an intragenic mutation. No evidently milder NF1 phenotype for patients with a missense mutation was observed. Forty-six prenatal analyses were performed in 28 (2.4%) families, of which 29 (63%) showed heterozygosity for the familial pathogenic mutation. This indicates that there is a need for prenatal NF1 testing.

(prenatal) molecular diagnostics, Clinical, Genetic, Neurofibromatosis type 1, The Netherlands
dx.doi.org/10.1111/cge.12187, hdl.handle.net/1765/60742
Clinical Genetics: an international journal of genetics and molecular medicine
Department of Clinical Genetics

Thornton, A.S, van Bever, Y, Kromosoeto, J.N.R, Withagen-Hermans, C.J, Nieuwlaat, A, Halley, D.J.J, & van den Ouweland, A.M.W. (2014). A clinical and genetic overview of 18years neurofibromatosis type 1 molecular diagnostics in the Netherlands. Clinical Genetics: an international journal of genetics and molecular medicine, 85(4), 318–327. doi:10.1111/cge.12187