Earliest clinical manifestations and natural history of neurofibromatosis type 2 (NF2) in childhood: A study of 24 patients
Earliest clinical manifestations and natural history of neurofibromatosis type 2 (NF2) in childhood: A study of 24 patients
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DOI：
10.1055/s-2005-837581
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发表时间：
2005-02-01
期刊：
影响因子：
1.4
通讯作者：
Pavone, L
中科院分区：
文献类型：
--
作者：
Ruggieri, M;Iannetti, P;Pavone, L
背景资料：2型神经纤维瘤病（NF 2）是一种常染色体显性遗传疾病，其特征是发生多种神经系统肿瘤、眼部异常和皮肤肿瘤。虽然传统上被认为是一种成人疾病，但最初的体征和/或症状可能在儿童时期很明显，并且通常无法识别。目的：本研究的目的是确定NF 2的最早临床表现，并观察NF 2儿童的临床病程和结局。研究方法：我们对24名患者（10名男性，14名女性;目前年龄为4至22岁）进行了回顾性（1990-1998年）和前瞻性（1998-2004年）研究，这些患者符合在卡塔尼亚大学和意大利罗马大学观察到的修订后（曼彻斯特）NF 2标准。结果如下：NF 2确诊前转诊的原因包括：1）眼科问题：早发性透镜混浊（n=3）;斜视（n=3）和弱视（n=3）（由于潜在的颅神经和/或脑肿瘤）; 2）耳鼻喉科问题：听力损失和耳鸣（n=2）在青少年早期被忽视或作为耳部感染治疗;声音嘶哑（n=1）或双调（n=1）; 3）神经功能障碍：继发于颅内脑膜瘤（n=1）或前庭神经鞘瘤（VS）（n=1）的癫痫发作，与脑干和/或脊髓肿瘤相关的神经功能障碍（n=7），孤立性和多发性颅神经缺损（n=10），以及继发于神经鞘瘤的周围神经病变（n=4）; 4）皮肤表现：神经鞘瘤误诊为神经纤维瘤，因为相关的皮肤白斑（n=2）;皮肤白斑（n=8）和皮肤肿瘤（n=3）。20%的患者有家族史。NF 2基因的分子遗传学分析显示，在所有5个家族性病例和2/10的散发病例分析典型的截断突变。结论：患有NF 2的儿童通常首先因眼部、细微皮肤或神经系统问题而就医，当他们后来因双侧VS或其他颅内肿瘤而出现更典型的症状时，才意识到这些问题的重要性。在这个年轻的年龄，临床过程是高度可变的，这取决于肿瘤负荷，早期手术干预，肿瘤切除术后的手术结果，和并发症。
Background: Neurofibromatosis type 2 (NF2) is an autosomal dominant disease characterised by the development of multiple nervous system tumours, ocular abnormalities, and skin tumours. Although classically considered a disease of adults, initial signs and/or symptoms may be evident in childhood and are often unrecognised. Objectives: The aim of this study was to identify the earliest clinical presentations of NF2 and to characterise the clinical course and outcome in children with NF2. Methods: We have performed a retrospective (years 1990-1998) and prospective (years 1998-2004) study of 24 patients (10 males, 14 females; currently aged 4 to 22 years) fulfilling the revised (Manchester) NF2 criteria seen at the Universities of Catania and Rome, Italy. Results: Causes of referral prior to a definitive diagnosis of NF2 were: 1) Ophthalmologic problems: early onset lens opacities (n=3); strabismus (n=3) and amblyopia (n=3) (due to underlying cranial nerves and/or brain tumours); 2) Otolaryngology problems: hearing loss and tinnitus (n=2) in early teens disregarded or treated as ear infections; hoarse (n=1) or bitonal (n=1) voice; 3) Neurological dysfunction: seizures secondary to intracranial meningioma (n=1) or vestibular schwannomas (VS) (n=1), neurological dysfunction related to brainstem and/or spinal cord tumours (n=7), isolated and multiple cranial nerve deficits (n=10), and peripheral neuropathy secondary to schwannomas (n=4); 4) Skin manifestations: schwannomas mis-diagnosed as neurofibromas because of associated cafe-au-lait spots (n=2); cafe-au-lait spots (n=8) and skin tumours (n=3). A family history was relevant in 20% of the patients. Molecular genetic analysis of the NF2 gene revealed typical truncating mutations in all the 5 familial cases and in 2/10 sporadic cases analysed. Conclusions: Children with NF2 often first come to medical attention because of ocular, subtle skin, or neurological problems the significance of which is realised when they later present with more classical symptoms due to bilateral VS or other intracranial tumours. The clinical course at this young age is highly variable, depending on tumour burden, early surgical intervention, surgical outcome after tumour resection, and complications.