Kim Sungmin, Lee Chang-Hyun, Choi Seok-Yong, Kim Myeong-Kyu, Jung Sung Taek
Department of Orthopedic Surgery, Chonnam National University Medical School and Hospital, 42 Jebong-ro, Dong-gu, Gwangju 61469, Korea.
Department of Biomedical Sciences, Chonnam National University Medical School, Hwasun 58128, Korea.
J Clin Med. 2022 Jun 27;11(13):3703. doi: 10.3390/jcm11133703.
Multiple hereditary exostoses (MHE) is a rare autosomal dominant skeletal disorder with a variety of clinical manifestations. We aimed to evaluate the general clinical phenotypic severity of MHE using our own scoring system and analyzed the risk factors associated with severe clinical phenotypes. In this study, 43 patients from 30 families were analyzed. The mutations were identified by direct sequencing of polymerase chain reaction-amplified genomic DNA or by multiplex ligation-dependent probe amplification. According to a new scoring system devised by the authors, the severity of the phenotype was assessed as mild, moderate, or severe based on the deformity of each segment, number of exostoses, leg length discrepancy, and functional limitations. Of 43 patients from 30 families, 39 patients (90.7%) and 24 families (80%) presented with EXT1 or EXT2 mutations. Patients with EXT1 mutations had a significantly worse phenotype than that of patients with EXT2 mutations or without any detectable mutation. The mean clinical score of patients with an EXT1 mutation (5.76; range, 2.0-8.0; SD = 1.60) was higher than that of patients with an EXT2 mutation (4.06; range, 2.0-7.0; SD = 1.47) or of those without any detectable mutation (4.63; range, 3.0-6.0; SD = 1.44; = 0.005). According to our classification system, more patients with EXT1 mutations had 'severe disease' than those with EXT2 mutations. Deformity scores were also higher in patients with EXT1 mutations ( = 0.018). In the multivariate analysis, the deformity score was found to be associated with the 'severe' class ( = 0.031). In conclusion, 90.7% of patients with MHE showed EXT mutations. Our scoring system showed reliable results. We suggest that the extent of deformity is an important factor in determining the phenotype of MHE and close monitoring for the development of severe disease is recommended in patients with high deformity scores.
多发性遗传性骨软骨瘤（MHE）是一种罕见的常染色体显性遗传性骨骼疾病，具有多种临床表现。我们旨在使用我们自己的评分系统评估MHE的一般临床表型严重程度，并分析与严重临床表型相关的危险因素。在本研究中，对来自30个家庭的43例患者进行了分析。通过聚合酶链反应扩增的基因组DNA直接测序或多重连接依赖探针扩增来鉴定突变。根据作者设计的新评分系统，基于每个节段的畸形、骨软骨瘤数量、腿长差异和功能限制，将表型严重程度评估为轻度、中度或重度。在来自30个家庭的43例患者中，39例患者（90.7%）和24个家庭（80%）存在EXT1或EXT2突变。EXT1突变患者的表型明显比EXT2突变患者或无任何可检测突变的患者更差。EXT1突变患者的平均临床评分为5.76（范围：2.0 - 8.0；标准差 = 1.60），高于EXT2突变患者（4.06；范围：2.0 - 7.0；标准差 = 1.47）或无任何可检测突变的患者（4.63；范围：3.0 - 6.0；标准差 = 1.44；P = 0.005）。根据我们的分类系统，EXT1突变患者中“严重疾病”的患者比EXT2突变患者更多。EXT1突变患者的畸形评分也更高（P = 0.018）。在多变量分析中，发现畸形评分与“严重”类别相关（P = 0.031）。总之，90.7%的MHE患者显示EXT突变。我们的评分系统显示出可靠的结果。我们建议畸形程度是决定MHE表型的一个重要因素，对于畸形评分高的患者，建议密切监测严重疾病的发展。
