NF1 mutations and clinical spectrum in patients with spinal neurofibromas
NF1 mutations and clinical spectrum in patients with spinal neurofibromas
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DOI：
10.1136/jmg.40.5.368
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发表时间：
2003-05-01
影响因子：
4
通讯作者：
Mautner, VF
中科院分区：
文献类型：
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作者：
Kluwe, L;Tatagiba, M;Mautner, VF
结果17例指标患者脊柱肿瘤症状的发病年龄从11岁到49岁不等（平均32.8岁）。除2例患者在11岁和14岁时出现症状外，其余15例指标患者均在成人年龄（22 ~ 43岁）出现症状。对于17名指数患者和3名家庭成员，我们可以根据MRI计算出脊柱受影响的神经根的数量：10名受试者在1至24个神经根中有肿瘤（图1A所示为单个肿瘤的例子），而另外10名受试者在所有38个脊髓神经根中都有肿瘤（图1B所示为例子）。有些神经根可能有不止一个肿瘤，但每个神经根肿瘤的确切数量无法确定。9名患者进行了手术干预，另一名患者进行了活检。根据病理报告，所有切除或活检的肿瘤均为神经纤维瘤。然而，一些肿瘤并非孤立的，MRI显示界限不清，因此我们不能排除其中一些是丛状神经纤维瘤的可能性。17例指标患者中有15例符合NIH的NF1诊断标准，即在每例患者中均发现以下两种或两种以上：6个或6个以上咖啡泡斑点，2个或2个以上任何类型的神经纤维瘤，或1个丛状神经纤维瘤；腋窝或腹股沟有雀斑；视神经胶质瘤;两个或多个利氏结节；明显的骨性病变；一级亲属（父母，兄弟姐妹或后代）根据上述NF1标准患有NF1。15另外两名患者（142号和42号）除了多发性脊柱肿瘤外没有其他NF1的体征，因此不符合NF1的诊断标准。42号患者的父亲有嗜铬细胞瘤，但没有NF1的进一步征象。虽然符合诊断标准，患者308和341除了脊柱肿瘤外，分别只有1个和7个咖啡区斑点。308号病人的诊断是由于他的女儿有多个脊柱肿瘤和两个以上的利希结节，因此符合NF1的最低标准。另外3例NF1患者来自2个家庭（824、5884、584/ 1号患儿），其神经纤维瘤少于10个，咖啡泡斑点少于5个。来自6个家庭的8例患者除多发性脊柱肿瘤外，没有或只有少量NF1相关症状。8例患者脊柱肿瘤均呈对称分布，其中6例患者38根脊神经均受影响。
RESULTS Clinical findings The age at onset of symptoms caused by spinal tumours in the 17 index patients varied from 11 to 49 years (mean 32.8 years). Apart from two patients who had symptoms at ages 11 and 14, all the other 15 index patients had symptoms at adult ages (22 to 43 years). For the 17 index patients and three family members, we could count the number of affected nerve roots of the spine based on MRI: 10 subjects had tumours in 1 to 24 (an example of a single tumour is shown in fig 1A) while the other 10 had tumours in all 38 spinal nerve roots (an example is shown in fig 1B). Some nerve roots probably had more than one tumour but the exact number of tumours in each nerve root could not be determined. Nine patients had surgical interventions and one other patient had a biopsy. According to the pathology report, all removed or biopsied tumours were neurofibromas. However, some tumours were not solitary and not well circumscribed as shown by MRI and we thus could not exclude the possibility that some of them were plexiform neurofibromas.Fifteen out of the 17 index patients met the NIH diagnostic criteria for NF1, that is, two or more of the following were found in each of them: six or more café au lait spots, two or more neurofibromas of any type, or one plexiform neurofibroma; axillary or inguinal freckling; optic glioma; two or more Lisch nodules; a distinct osseous lesion; a first degree relative (parent, sib, or offspring) with NF1 according to the above criteria for NF1. 15 Two other patients (Nos 142 and 42) had no additional signs of NF1 besides the multiple spinal tumours and thus did not meet the diagnostic criteria for NF1. The father of patient 42 had a phaeochromocytoma but no further sign of NF1. Although fulfilling the diagnostic criteria, patients 308 and 341 had only one and seven café au lait spots, respectively, besides spinal tumours. The diagnosis for patient 308 was made possible by the diagnosis of his daughter who had multiple spinal tumours and more than two Lisch nodules and thus met the minimum criteria for NF1. Three other NF1 patients from two families (Nos 824, 584, 584/child 1) had fewer than 10 neurofibromas and fewer than five café au lait spots. In total, eight patients from six families had no or only a few additional NF1 associated symptoms besides the multiple spinal tumours. In all these eight patients spinal tumours were distributed symmetrically and in six of them all 38 spinal nerve roots were affected.