Importance Neurofibromatosis type 2 (NF2) is a devastating genetic condition characterized by the development of multiple tumors of the nervous system. An early diagnosis of individuals with NF2 would facilitate treatment and reduction of disease impact because most severe effects of the disease do not usually develop before adolescence. Little attention has traditionally been paid to dermatological signs in NF2. However, skin plaques are commonly seen in patients with NF2, normally appearing either at birth or early childhood, providing an opportunity for early NF2 detection and testing.

Objective To determine the clinical utility of skin plaque identification and characterization in children for reaching an early diagnosis of patients with NF2 and to evaluate their molecular pathogenesis and their use in the genetic diagnostics of NF2.

Design, Setting, and Participants Diagnostic test study by the histological and genetic characterization of skin plaques from patients with NF2. Patients were 7 individuals with NF2 or clinical suspicion of NF2 treated at the Spanish Reference Center on Phakomatoses.

Main Outcomes and Measures Histological evaluation of all skin plaques was performed. Fresh skin plaques were cultured to obtain Schwann cells and the NF2 gene was genetically analyzed. For all 7 patients, NF2 clinical history was reviewed.

Results In all 7 patients (4 male and 3 female), all skin plaques analyzed were histologically characterized as plexiform schwannomas. Genetic analysis of primary Schwann cell cultures derived from them allowed the identification of a constitutional and a somatic NF2 mutation. Genetic testing allowed the early diagnosis of NF2 in a child only exhibiting the presence of skin plaques. Most of the patients with NF2 analyzed had an early presentation of skin plaques and a severe NF2 phenotype.

Conclusions and Relevance This work emphasizes the clinical utility of a careful dermatological inspection and the correct identification of skin plaques in children for an early diagnosis of NF2. We show for the first time that Schwann cells derived from skin plaque plexiform schwannomas bear the double inactivation of the NF2 gene and thus constitute an excellent source of tissue for genetic testing, especially in the context of mosaicism.

重要性 2型神经纤维瘤病（NF2）是一种破坏性遗传病，其特征是神经系统的多个肿瘤发展。早期诊断患有NF2的个体将有助于治疗并减少疾病的影响，因为该疾病的最严重影响通常不会在青春期之前出现。传统上，很少关注NF2中的皮肤病学症状。但是，NF2患者通常见到皮肤斑块，通常出现在出生时或儿童早期，为早期NF2检测和测试提供了机会。

目的 确定儿童皮肤斑块鉴定和表征在早期诊断NF2患者中的临床效用，并评估其分子发病机理及其在NF2基因诊断中的应用。

设计，设置和参与者 通过对NF2患者皮肤斑块的组织学和遗传学特征进行诊断测试研究。患者为7名患有NF2的个体，或在西班牙Phomamatose参考中心接受治疗的NF2临床怀疑者。

主要结果和措施 对所有皮肤斑块进行组织学评估。培养新鲜的皮肤斑块以获得雪旺氏细胞，并且对NF2基因进行遗传分析。回顾了所有7例患者的NF2临床病史。

结果 在所有7例患者中（4例男性和3例女性），所有被分析的皮肤斑块在组织学上均被表征为丛状神经鞘瘤。对源自它们的原始雪旺氏细胞培养物的遗传分析允许鉴定体质和体细胞NF2突变。基因检测可以对仅表现出皮肤斑块的儿童进行NF2的早期诊断。分析的大多数NF2患者早期出现皮肤斑块和严重的NF2表型。

结论与相关性 这项工作强调了对儿童进行早期皮肤病学检查和正确识别皮肤斑块以早期诊断NF2的临床效用。我们首次表明，源自皮肤斑块状神经鞘瘤的雪旺细胞具有NF2基因的双重失活，因此构成了用于基因测试的极好的组织来源，尤其是在镶嵌的情况下。