| Summary: | <p>Abstract</p> <p>Introduction</p> <p>Large deletions of the <it>NF1 </it>gene and its flanking regions are frequently associated with a severe clinical manifestation. Different types of gross <it>NF1 </it>deletion have been identified that are distinguishable both by their size and the number of genes included within the deleted regions. Type-1 <it>NF1 </it>deletions encompass 1.4 Mb and include 14 genes, whereas the much less common type-2 <it>NF1 </it>deletions span 1.2 Mb and contain 13 genes. Genotype-phenotype correlations in patients with large <it>NF1 </it>deletions are likely to be influenced by the nature and number of the genes deleted in addition to the <it>NF1 </it>gene. Whereas the clinical phenotype associated with type-1 <it>NF1 </it>deletions has been well documented, the detailed clinical characterization of patients with non-mosaic type-2 <it>NF1 </it>deletions has not so far been reported.</p> <p>Case presentation</p> <p>In the present report we characterized two Caucasian European patients with non-mosaic (germline) type-2 <it>NF1 </it>deletions. Our first patient was a 13-year-old girl with dysmorphic facial features, mild developmental delay, large hands and feet, hyperflexibility of the joints, macrocephaly and T2 hyperintensities in the brain. A whole-body magnetic resonance imaging scan indicated two internal plexiform neurofibromas. Our second patient was an 18-year-old man who exhibited dysmorphic facial features, developmental delay, learning disability, large hands and feet, hyperflexibility of the joints, macrocephaly and a very high subcutaneous and internal tumor load as measured volumetrically on whole-body magnetic resonance imaging scans. At the age of 18 years, he developed a malignant peripheral nerve sheath tumor and died from secondary complications. Both our patients exhibited cardiovascular malformations.</p> <p>Conclusions</p> <p>Our two patients with non-mosaic type-2 <it>NF1 </it>deletions exhibited clinical features that have been reported in individuals with germline type-1 <it>NF1 </it>deletions. Therefore, a severe disease manifestation is not confined to only patients with type-1 <it>NF1 </it>deletions but may also occur in individuals with type-2 <it>NF1 </it>deletions. Our findings support the concept of an <it>NF1 </it>microdeletion syndrome with severe clinical manifestation that is caused by type-1 as well as type-2 <it>NF1 </it>deletions.</p>
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