PMC4711050_01
Clinical and radiologic presentation of the index PS patient. a Overgrowth of the feet (left panel) with radiologic confirmation of bone overgrowth, especially of the left foot (righ panel). b Severe cyphoscoliosis of the index patient. c Length discrepancy and macrodactyly in the III and IV fingers of right hand from the index patient. d e and f Coronal flair (d) and axial flair (e) weighted images demonstrated hyperostosis of the right fronto-parietal cranial vault (black asterisk) with proptosis of the right eye and extensive malformation of cortical development involving predominantly the right cerebral hemisphere but also part of the left cerebral hemisphere. There is an extensive white matter signal abnormality of both hemispheres (white arrows); there is also an associated malformation of the brainstem. Coronal T2 weighted images (f) show hyperostosis of the right fronto-parietal cranial vault (black asterisk), extensive malformation of the right hemisphere with white matter changes in the periventricular region (white arrows); malformation of cortex in the left perisylvian region (red arrow)
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Fig1
The index patient presented important overgrowth of the feet (Fig. 1a, left panel) with greater growth of the calcaneus and cuboid, especially of the left foot (Fig. 1a, right panel). The patient also presented severe kyphoscoliosis (Fig. 1b) and length discrepancy and macrodactyly in the III and IV fingers of right hand (Fig. 1c), emphysema, pulmonary fibrosis, syringomyelic cavity of about 2 cm in the section C3-D4, and ovarian cystadenomas. Brain magnetic resonance imaging (MRI) showed cortical dysplasia with marked thickening of the skull in the right fronto-temporal (Fig. 1d, e and f) which increased in volume over 4 years reaching 44 mm with significant compression on the midbrain, brain parenchyma and cerebral edema, hydrocephalus and proptosis of the right eye (Fig. 1e).
B cell in vitro activation from the index patient. a B cells from the index patient and a healthy control (HD) were stimulated with CpG and CD69 up-regulation was evaluated by flow-cytometry after overnight incubation. b B cells from the index patient and a healthy control (HD) were stimulated with CpG and CD86 up-regulation was evaluated by flow-cytometry after overnight incubation. Red circles depict the activated cell populations
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Fig2
Patient's B cells on the other hand showed an increased up-regulation of CD69 and CD86 upon CpG stimulation when compared to the healthy control (Fig. 2a and b respectively), suggestive of B cell hyper responsiveness in PS.