Proteus syndrome is a rare genetic disorder, which is characterized by progressive, segmental, or patchy overgrowth of diverse tissues of all germ layers, including the skeleton. Here, we present a 9-year-old girl with a somatic-activating mutation (c.49G > A; p.Glu17Lys) in AKT1 gene in a mosaic status typical for Proteus syndrome. She presented with hemihypertrophy of the right lower limb and a “moccasin” lesion among others. A transiliac bone biopsy was analyzed for bone histology/histomorphometry as well as bone mineralization density distribution (BMDD) and osteocyte lacunae sections (OLS) characteristics based on quantitative backscattered electron imaging. Bone histomorphometry revealed highly increased mineralizing surface (Z-score + 2.3) and mineral apposition rate (Z-score + 19.3), no osteoclasts (Z-score − 2.1), and an increased amount of primary bone in the external cortex. BMDD abnormalities included a decreased mode calcium concentration in cancellous bone (Z-score − 1.7) and an increased percentage of highly mineralized cortical bone area (Z-score + 2.4) compared to reference. OLS characteristics showed several differences compared to reference data; among them, there were the highly increased OLS-porosity, OLS-area, and OLS-perimeter on the external cortex (Z-scores + 6.8, + 4.4 and 5.4, respectively). Our findings suggest that increased bone formation reduced matrix mineralization in cancellous bone while the enhanced amount of primary bone in the external cortex increased the portion of highly mineralized cortical bone and caused OLS-characteristics abnormalities. Our results indicate further that remodeling of primary bone might be disturbed or delayed in agreement with the decreased number of osteoclasts observed in this child with Proteus syndrome.

Proteus 综合征是一种罕见的遗传性疾病，其特征是所有胚层的不同组织（包括骨骼）进行性、节段性或斑片状过度生长。在这里，我们展示了一个 9 岁女孩的AKT1体细胞激活突变（c.49G > A；p.Glu17Lys）Proteus 综合征典型的镶嵌状态中的基因。她表现为右下肢偏侧肥大和“莫卡辛”病变等。基于定量背散射电子成像分析经髂骨活检的骨组织学/组织形态学以及骨矿化密度分布 (BMDD) 和骨细胞陷窝切片 (OLS) 特征。骨组织形态测量显示矿化表面高度增加（Z-score + 2.3）和矿物质沉积率（Z-score + 19.3），无破骨细胞（Z-score - 2.1），以及外皮层原生骨量增加。与参考相比，BMDD 异常包括松质骨中模式钙浓度降低（Z 分数 - 1.7）和高度矿化皮质骨面积百分比增加（Z 分数 + 2.4）。与参考数据相比，OLS 特征显示出一些差异；其中，外皮层的 OLS 孔隙率、OLS 面积和 OLS 周长高度增加（Z 分数分别为 + 6.8、+ 4.4 和 5.4）。我们的研究结果表明，增加的骨形成减少了松质骨中的基质矿化，而外皮质中初级骨量的增加增加了高度矿化的皮质骨的比例并导致 OLS 特征异常。我们的结果进一步表明，与在这个患有变形杆菌综合征的儿童中观察到的破骨细胞数量减少一致，初级骨的重塑可能会受到干扰或延迟。+ 4.4 和 5.4，分别）。我们的研究结果表明，增加的骨形成减少了松质骨中的基质矿化，而外皮质中初级骨量的增加增加了高度矿化的皮质骨的比例并导致 OLS 特征异常。我们的结果进一步表明，与在这个患有变形杆菌综合征的儿童中观察到的破骨细胞数量减少一致，初级骨的重塑可能会受到干扰或延迟。+ 4.4 和 5.4，分别）。我们的研究结果表明，增加的骨形成减少了松质骨中的基质矿化，而外皮质中初级骨量的增加增加了高度矿化的皮质骨的比例并导致 OLS 特征异常。我们的结果进一步表明，与在这个患有变形杆菌综合征的儿童中观察到的破骨细胞数量减少一致，初级骨的重塑可能会受到干扰或延迟。