BACKGROUND The Proteus syndrome is characterized by the overgrowth of skin, connective tissue, brain, and other tissues. It has been hypothesized that the syndrome is caused by somatic mosaicism for a mutation that is lethal in the nonmosaic state. METHODS We performed exome sequencing of DNA from biopsy samples obtained from patients with the Proteus syndrome and compared the resultant DNA sequences with those of unaffected tissues obtained from the same patients. We confirmed and extended an observed association, using a custom restriction-enzyme assay to analyze the DNA in 158 samples from 29 patients with the Proteus syndrome. We then assayed activation of the AKT protein in affected tissues, using phosphorylation-specific antibodies on Western blots. RESULTS Of 29 patients with the Proteus syndrome, 26 had a somatic activating mutation (c.49G→A, p.Glu17Lys) in the oncogene AKT1, encoding the AKT1 kinase, an enzyme known to mediate processes such as cell proliferation and apoptosis. Tissues and cell lines from patients with the Proteus syndrome harbored admixtures of mutant alleles that ranged from 1% to approximately 50%. Mutant cell lines showed greater AKT phosphorylation than did control cell lines. A pair of single-cell clones that were established from the same starting culture and differed with respect to their mutation status had different levels of AKT phosphorylation. CONCLUSIONS The Proteus syndrome is caused by a somatic activating mutation in AKT1, proving the hypothesis of somatic mosaicism and implicating activation of the PI3K–AKT pathway in the characteristic clinical findings of overgrowth and tumor susceptibility in this disorder. (Funded by the Intramural Research Program of the National Human Genome Research Institute.)

Femoral lengthening with the Precice femoral nail achieved excellent functional results with fewer complications and greater patient satisfaction when compared with the LRS system in our patients. Cite this article: Bone Joint J 2016;98-B:1382-8.

Aims The Precice intramedullary limb-lengthening system has demonstrated significant benefits over external fixation lengthening methods, leading to a paradigm shift in limb lengthening. This study compares outcomes following antegrade and retrograde femoral lengthening in both adolescent and adult patients. Patients and Methods A retrospective review of prospectively collected data was undertaken of a consecutive series of 107 femoral lengthening operations in 92 patients. In total, 73 antegrade nails and 34 retrograde nails were inserted. Outcome was assessed by the regenerate healing index (HI), hip and knee range of movement (ROM), and the presence of any complications. Results The mean lengthening was 4.65 cm (1.5 to 8) in the antegrade group and 4.64 cm (1.6 to 8) in the retrograde group. Of the 107 lengthenings, 100 had sufficient datapoints to calculate the mean HI. This was 31.6 days/cm (15 to 108). There was a trend toward a lower (better) HI with an antegrade nail and better outcomes in adolescent patients, but these were not statistically significant. Hip and knee ROM was maintained and/or improved following commencement of femoral lengthening in 44 patients (60%) of antegrade nails and 13 patients (38%) of retrograde nails. In female patients, loss of movement occurred both earlier and following less total length achieved. Minor implant complications included locking bolt migration and in one patient deformity of the nail, but no implant failed to lengthen and there were no deep infections. Three patients had delayed union, five patients required surgical intervention for joint contracture. Conclusion This study confirms excellent results in femoral lengthening with antegrade and retrograde Precice nails. There is a trend for better healing and less restriction in hip and knee movement following antegrade nails. There are clinical scenarios, that mandate the use of a retrograde nail. However, when these are not present, we recommend the use of antegrade nailing. Cite this article: Bone Joint J 2019;101-B:1168–1176

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