Child's Nervous System ( IF 1.4 ) Pub Date : 2020-06-15 , DOI: 10.1007/s00381-020-04729-w Isabel Gugel 1, 2 , Florian Grimm 1 , Christian Teuber 1 , Julian Zipfel 1, 2, 3 , Marcos Tatagiba 1, 2 , Victor-Felix Mautner 2, 4 , Martin Ulrich Schuhmann 1, 2, 4 , Lan Kluwe 4, 5
Purpose
The hallmark of neurofibromatosis type 2 (NF2) is the presence of bilateral vestibular schwannomas (VS) which however have not yet developed or grown to large size in children and young adolescents. Therefore, early diagnosis in pediatric patients without family history of NF2 has to be made by signs and symptoms not related to VS which will be reviewed in this study.
Methods
A total of 70 children diagnosed for NF2 at an age of < 18 years were identified from our patient cohort. Age and symptoms, signs and pathology at symptom onset, age at NF2 diagnosis and symptoms leading to diagnosis as well as genetic findings were retrospectively reviewed.
Results
The average age at symptom/sign onset was 8 ± 6 (range 0–17) years and 11 ± 5 (range 1–17) years at time of diagnosis. Fifteen children had a positive family history and were diagnosed upon additional clinical symptoms. The most frequent first presenting symptom/signs were ophthalmological abnormalities (49%), followed by cutaneous features (40%), non-VS-related neurological deficits (33%), and symptoms attributable to VS (21%). VS were not only the most common symptomatic neoplasm but also the most frequent pathological evidence for the diagnosis (72%). In 42 patients with available genetic testing results, pathogenic mutations were most frequently identified (n = 27).
Conclusion
The presenting symptoms in NF2 children appear “unspecific” or less specific for classical NF2 compared with adult NF2 patients, posing a challenge particularly for cases without family history. In children, ophthalmological and cutaneous features should raise clinical suspicion for NF2 and referral to an NF2 specialized center is recommended.
中文翻译:
在2型神经纤维瘤病儿童中出现症状
目的
2型神经纤维瘤病(NF2)的标志是双侧前庭神经鞘瘤(VS)的存在,但尚未在儿童和青少年中发展或长成较大的规模。因此,必须通过与VS不相关的体征和症状对没有NF2家族史的小儿患者进行早期诊断,本研究将对此进行综述。
方法
从我们的患者队列中,总共鉴定出70位年龄小于18岁的被诊断为NF2的儿童。回顾性分析年龄和症状,症状发作时的体征和病理,NF2诊断时的年龄和导致诊断的症状以及遗传发现。
结果
诊断时,症状/体征的平均年龄为8±6岁(0-17岁)和11±5岁(1-17岁)。15名儿童有积极的家族史,并根据其他临床症状被诊断出。最先出现的症状/体征是眼科异常(49%),其次是皮肤特征(40%),与VS不相关的神经功能缺损(33%)和可归因于VS的症状(21%)。VS不仅是最常见的症状性肿瘤,而且是诊断的最常见病理学证据(72%)。在有可用基因检测结果的42例患者中,最常发现致病突变(n = 27)。
结论
与成年NF2患者相比,NF2儿童中出现的症状对经典NF2表现为“无特异性”或较低特异性,尤其对没有家族史的患者构成挑战。对于儿童,眼科和皮肤特征应引起对NF2的临床怀疑,建议转诊至NF2专业中心。