Vogt et al. Journal of Medical Case Reports 2011, 5:577 http://www.jmedicalcasereports.com/content/5/1/577 whom mosaicism could not be detected were considered to be probable germline type-2 deletions. In the present study, we describe the clinical features of two patients with non-mosaic type-2 NF1 deletions and compare their phenotypes to those of patients with type-1 NF1 deletions. Our aim was to assess whether obvious differences exist in relation to the clinical phe- notypes associated with these two different types of NF1 deletion. Case presentation The characterization of the deletion breakpoints of both patients (2429 and 2358 in [13]) studied here has been reported previously [13]. Breakpoint analysis indicated that the deletions were mediated by NAHR between the SUZ12 gene and SUZ12P. Neither FISH performed on blood samples nor microsatellite marker analysis using DNA from buccal swabs yielded any evidence for somatic mosaicism with normal cells in both patients [13]. In our first patient (patient 2358 in [13]), FISH was performed on interphase cells derived from an urine sample according to the methods described previously [12]; of 307 nuclei evaluated > 99% exhibited the dele- tion. We conclude that it is likely that both patients har- bor non-mosaic (germline) type-2 NF1 deletions. Patient 1 Our first patient was a prematurely born girl of Cauca- sian European descent, with a patent foramen ovale with a minor left-to-right cardiac shunt and pulmonary valve stenosis (PVS) at birth. However, the PVS dimin- ished over time. During her pre-school years, she exhib- ited mild motor and cognitive developmental delay. At the age of five years, delays in speech and the develop- ment of articulation were diagnosed. Clinical examina- tion at the age of 12 years and nine months indicated normal height and weight (160 cm (50th to 75th percen- tile) and 59 kg (75th to 90th percentile)). However, macrocephaly was noted with a head circumference of 56.8 cm (97th percentile). Facial dysmorphic features including hypertelorism, epicanthic folds, a broad nasal root and low set ears were observed. She had large hands and feet and hyperflexibility of the joints. More than six café-au-lait spots were noted as well as axillary and inguinal freckling, Lisch nodules and 10 subcuta- neous neurofibromas. She had slight hypertrichosis on her lower back and a length difference of the legs. Neu- rological examination indicated generalized muscular hypotonia, but she showed adequate coordination and motor function. Whole body MRI revealed a small plexi- form neurofibroma of the right calf (9.2 mL, Figure 2A, B) and an internal plexiform neurofibroma above the right ankle (Figure 2C). Neither large occult tumors, nor spinal neurofibromas were identified on whole-body Page 3 of 7 MRI scans (Figure 2A). MRI of the brain revealed T2 hyperintensities in the cerebellum, which are thought to represent foci of neural dysplasia or dysmyelination. Neuropsychological testing was not performed. Initially, our patient attended a regular elementary school and then, at the age of 12 years and nine months, secondary school. Severe learning disabilities were not reported, but owing to attention deficit and impairment in speed of learning, she needed educational support. Patient 2 Our second patient was a man of Caucasian European descent who had shown considerable motor and cogni- tive developmental delay as a child in his pre-school years. He was clinically examined by us at the age of 18 years. His body measures were within the normal range (height: 184 cm (50th to 75th percentile), weight: 62 kg (10th to 25th percentile)). However, macrocephaly was noted (head circumference: 60 cm (97th percentile)). He had large hands and feet and hyperflexibility of the joints. Facial dysmorphic features including saddle nose and hypertelorism were noted, as well as a broad neck and a funnel chest (Figure 3A). A difference in length between his legs was noted but his spine was in an orthograde position. MRI of his brain revealed complex corpus callosum aplasia. Neuropsychological examina- tion revealed significant visual motor and attention defi- cits. IQ testing indicated a full scale IQ of 84, a verbal IQ of 86 and a performance IQ of 85. Our patient attended regular elementary school and obtained a sec- ondary school certificate. He had more than six café-au-lait spots and axillary and inguinal freckling as well as Lisch nodules. Cardiac exami- nation showed a right ventricular subvalvular neurofi- broma (17 × 17 mm), which resulted in a first-degree pulmonary valve insufficiency. More than 1000 subcuta- neous and 500 cutaneous neurofibromas were noted (Fig- ure 3B). Volumetric analysis of whole body MRI scans indicated a high internal total tumor load of 3896 mL. Large plexiform neurofibromas (PNs) were detected along the lumbo-sacral plexus and in the abdomen/pelvis. Smal- ler PNs were detected within the right lower limb, para- pharyngeal space, along the brachial plexus and spinal nerves as well as major peripheral nerves (Figure 4A-C). Our patient’s primary MPNST (WHO grade IV) evolved from a pre-existing PN located in the lesser pelvis affecting the lumbar vertebra L5 and leading to osteolysis of his sacral and ileac bone. Seven months after surgery, our patient experienced severe abdominal pain and relapse was evident on MRI and PET-CT scan (standardized uptake value (SUV) of 11,5, Figure 4D, E). Our patient underwent surgery and adjuvant chemotherapy (CWS protocol) but post-operative staging revealed tumor infil- tration of the intestine up to the left colon flexure and