Vogt et al. Journal of Medical Case Reports 2011, 5:577 http://www.jmedicalcasereports.com/content/5/1/577 C A S E R E P O R T JOURNAL OF MEDICAL CASE REPORTS Open Access Delineation of the clinical phenotype associated with non-mosaic type-2 NF1 deletions: two case reports Julia Vogt1, Rosa Nguyen2,3, Lan Kluwe3, Martin Schuhmann5, Angelika C Roehl1, Tanja Mußotter1, David N Cooper4, Victor-Felix Mautner6 and Hildegard Kehrer-Sawatzki1* Abstract Introduction: Large deletions of the NF1 gene and its flanking regions are frequently associated with a severe clinical manifestation. Different types of gross NF1 deletion have been identified that are distinguishable both by their size and the number of genes included within the deleted regions. Type-1 NF1 deletions encompass 1.4 Mb and include 14 genes, whereas the much less common type-2 NF1 deletions span 1.2 Mb and contain 13 genes. Genotype-phenotype correlations in patients with large NF1 deletions are likely to be influenced by the nature and number of the genes deleted in addition to the NF1 gene. Whereas the clinical phenotype associated with type-1 NF1 deletions has been well documented, the detailed clinical characterization of patients with non-mosaic type-2 NF1 deletions has not so far been reported. Case presentation: In the present report we characterized two Caucasian European patients with non-mosaic (germline) type-2 NF1 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. Conclusions: Our two patients with non-mosaic type-2 NF1 deletions exhibited clinical features that have been reported in individuals with germline type-1 NF1 deletions. Therefore, a severe disease manifestation is not confined to only patients with type-1 NF1 deletions but may also occur in individuals with type-2 NF1 deletions. Our findings support the concept of an NF1 microdeletion syndrome with severe clinical manifestation that is caused by type-1 as well as type-2 NF1 deletions. Introduction Neurofibromatosis type I (NF1) is an autosomal-domi- nant inherited disease with an estimated frequency of 1:3000 [1]. The classic hallmarks of NF1 include café- au-lait spots, axillary and inguinal freckling, neurofibro- mas and Lisch nodules. Approximately 95% of all patients with NF1 harbor mutations within the NF1 * Correspondence: hildegard.kehrer-sawatzki@uni-ulm.de 1Institute of Human Genetics, University of Ulm, Ulm, Germany Full list of author information is available at the end of the article gene, whereas 5% have large deletions that encompass the NF1 gene and its flanking regions [2]. From a clini- cal point of view, the molecular diagnosis of a large NF1 deletion is important because they are frequently asso- ciated with severe clinical manifestations [3-6] including an increased risk of malignant peripheral nerve sheath tumors (MPNSTs) as compared with the general NF1 population [7]. MPNSTs and gliomas together represent the most common causes of reduced life expectancy among patients with NF1 [8]. © 2011 Vogt et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.