Jordan Justin T, Smith Miriam J, Walker James A, Erdin Serkan, Talkowski Michael E, Merker Vanessa L, Ramesh Vijaya, Cai Wenli, Harris Gordon J, Bredella Miriam A, Seijo Marlon, Suuberg Alessandra, Gusella James F, Plotkin Scott R
Department of Neurology Cancer Center, Massachusetts General Hospital, Boston, MA Centre for Genomic Medicine, St Mary's Hospital, Division of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, Manchester, UK Molecular Neurogenetics Unit, Center for Genomic Medicine Department of Radiology, Massachusetts General Hospital and Harvard Medical School Department of Genetics, Harvard Medical School, Boston, MA.
Medicine (Baltimore). 2018 Feb;97(5):e9717. doi: 10.1097/MD.0000000000009717.
Schwannomatosis has been linked to germline mutations in the SMARCB1 and LZTR1 genes, and is frequently associated with pain.In a cohort study, we assessed the mutation status of 37 patients with clinically diagnosed schwannomatosis and compared to clinical data, whole body MRI (WBMRI), visual analog pain scale, and Short Form 36 (SF-36) bodily pain subscale.We identified a germline mutation in LZTR1 in 5 patients (13.5%) and SMARCB1 in 15 patients (40.5%), but found no germline mutation in 17 patients (45.9%). Peripheral schwannomas were detected in 3 LZTR1-mutant (60%) and 10 SMARCB1-mutant subjects (66.7%). Among those with peripheral tumors, the median tumor number was 4 in the LZTR1 group (median total body tumor volume 30 cc) and 10 in the SMARCB1 group (median volume 85cc), (P=.2915 for tumor number and P = .2289 for volume). mutation was associated with an increased prevalence of spinal schwannomas (100% vs 41%, P = .0197). The median pain score was 3.9/10 in the LZTR1 group and 0.5/10 in the SMARCB1 group (P = .0414), and SF-36 pain-associated quality of life was significantly worse in the LZTR1 group (P = .0106). Pain scores correlated with total body tumor volume (rho = 0.32471, P = .0499), but not with number of tumors (rho = 0.23065, P = .1696).We found no significant difference in quantitative tumor burden between mutational groups, but spinal schwannomas were more common in LZTR1-mutant patients. Pain was significantly higher in LZTR1-mutant than in SMARCB1-mutant patients, though spinal tumor location did not significantly correlate with pain. This suggests a possible genetic association with schwannomatosis-associated pain.
神经鞘瘤病与SMARCB1和LZTR1基因的种系突变有关，且常伴有疼痛。在一项队列研究中，我们评估了37例临床诊断为神经鞘瘤病患者的突变状态，并将其与临床数据、全身磁共振成像（WBMRI）、视觉模拟疼痛量表以及简明健康状况调查量表（SF - 36）的身体疼痛分量表进行比较。我们在5例患者（13.5%）中发现了LZTR1种系突变，在15例患者（40.5%）中发现了SMARCB1种系突变，但在17例患者（45.9%）中未发现种系突变。在3例LZTR1突变（60%）和10例SMARCB1突变受试者（66.7%）中检测到周围神经鞘瘤。在患有周围肿瘤的患者中，LZTR1组的肿瘤中位数为4个（全身肿瘤总体积中位数为30立方厘米），SMARCB1组为10个（体积中位数为85立方厘米），（肿瘤数量P = 0.2915，体积P = 0.2289）。LZTR1突变与脊柱神经鞘瘤的患病率增加相关（100%对41%，P = 0.0197）。LZTR1组疼痛评分中位数为3.9/10，SMARCB1组为0.5/10（P = 0.0414），并且LZTR1组中SF - 36疼痛相关生活质量明显更差（P = 0.0106）。疼痛评分与全身肿瘤体积相关（rho = 0.32471，P = 0.0499），但与肿瘤数量无关（rho = 0.23065，P = 0.1696）。我们发现突变组之间在定量肿瘤负荷方面没有显著差异，但脊柱神经鞘瘤在LZTR1突变患者中更常见。LZTR1突变患者的疼痛明显高于SMARCB1突变患者，尽管脊柱肿瘤位置与疼痛没有显著相关性。这表明可能存在与神经鞘瘤病相关疼痛的遗传关联。
