Department of Genomic Medicine, St Mary's Hospital, Manchester Academic Health Sciences Centre (MAHSC), Division of Evolution and Genomic Science, University of Manchester, Manchester, UK.
Department of Neurosurgery, Manchester Centre for Clinical Neurosciences, Salford Royal Foundation Trust, Manchester Academic Health Sciences Centre (MAHSC), Manchester, UK.
Genet Med. 2019 Jul;21(7):1525-1533. doi: 10.1038/s41436-018-0384-y. Epub 2018 Dec 7.
We have evaluated deficiencies in existing diagnostic criteria for neurofibromatosis 2 (NF2).
Two large databases of individuals fulfilling NF2 criteria (n = 1361) and those tested for NF2 variants with criteria short of diagnosis (n = 1416) were interrogated. We assessed the proportions meeting each diagnostic criterion with constitutional or mosaic NF2 variants and the positive predictive value (PPV) with regard to definite diagnosis.
There was no evidence for usefulness of old criteria "glioma" or "neurofibroma." "Ependymoma" had 100% PPV and high levels of confirmed NF2 diagnosis (67.7%). Those with bilateral vestibular schwannoma (VS) alone aged ≥60 years had the lowest confirmation rate (6.6%) and reduced PPV (80%). Siblings as a first-degree relative, without an affected parent, had 0% PPV. All three individuals with unilateral VS and an affected sibling were proven not to have NF2. The biggest overlap was with LZTR1-associated schwannomatosis. In this category, seven individuals with unilateral VS plus ≥2 nondermal schwannomas reduced PPV to 67%.
The present study confirms important deficiencies in NF2 diagnostic criteria. The term "glioma" should be dropped and replaced by "ependymoma." Similarly "neurofibroma" should be removed. Dropping "sibling" from first-degree relatives should be considered and testing of LZTR1 should be recommended for unilateral VS.
我们评估了神经纤维瘤病 2 型（NF2）现有诊断标准的缺陷。
对符合 NF2 标准的个体的两个大型数据库（n=1361）和不符合诊断标准但进行 NF2 变体检测的个体的数据库（n=1416）进行了调查。我们评估了每个诊断标准与核型或嵌合体 NF2 变体的符合率，以及对明确诊断的阳性预测值（PPV）。
旧标准“神经胶质瘤”或“神经纤维瘤”没有证据表明其有用性。“室管膜瘤”的 PPV 为 100%，且确诊 NF2 的比例很高（67.7%）。仅双侧前庭神经鞘瘤（VS）且年龄≥60 岁的患者确诊率最低（6.6%），PPV 降低（80%）。作为一级亲属、无患病父母的兄弟姐妹的 PPV 为 0%。所有 3 名单侧 VS 且有患病兄弟姐妹的患者均未确诊为 NF2。与 LZTR1 相关的雪旺细胞瘤的重叠最大。在这一类中，7 名单侧 VS 加≥2 个非皮肤神经鞘瘤的患者，PPV 降至 67%。
本研究证实了 NF2 诊断标准的重要缺陷。“神经胶质瘤”一词应被删除，代之以“室管膜瘤”。同样，“神经纤维瘤”也应被删除。应考虑从一级亲属中删除“兄弟姐妹”，并推荐对单侧 VS 进行 LZTR1 检测。
