人们对皮肤神经纤维瘤 (cNF) 的治疗开发越来越感兴趣，皮肤神经纤维瘤是 1 型神经纤维瘤病 (NF1) 患者发病的主要原因。为了确定有意义的临床试验结果，需要更深入地了解 cNF 与生活质量 (QoL) 的关系。然而，这种理解受到了招募患有这种罕见遗传病的参与者的挑战的阻碍。开发一个大型、众包的经过验证的 NF1 患者登记册，并确定特定 cNF 特征与生活质量、疼痛和瘙痒的关联。从 2021 年 5 月到2023年12月，开发了一个去中心化平台，并从49个州和12个国家招募了40岁或以上患有NF1和至少1个cNF的人员，他们提供了临床调查数据、详细照片和基因测序数据。对 583 名参与者的照片进行了 12 个 cNF 特征的评分，包括一般严重程度、数量、大小、面部严重程度、颜色和亚型。cNF 特征源自参与者提供的照片。总 Skindex 分数和子领域分数（症状、情绪、功能、 583 名参与者中，384 名（65.9%）为女性，平均（范围）年龄为 51.7（40.0-83.0）岁。女性性别、cNF 的一般严重程度、数量、大小和面部严重程度与生活质量呈负相关，Skindex 总分的增加证明了这一点。生活质量与 cNF 的数量和面部 cNF 的存在关系最大。 cNF 数量的增加与较差的生活质量相关，甚至 cNF 负担较低（总 cNF 数<10）的个体的生活质量也会下降。这项研究的结果表明，减少 cNF 数量，尤其是面部的 cNF 数量，可能与以下因素有关：改善 NF1 患者的生活质量。此外，在多种肿瘤发生之前进行早期干预可能会带来最大的生活质量益处。这些数据可能有助于了解哪些个体和 cNF 肿瘤可能从治疗中获益最多，并强调了完全分散、经过照片验证和年龄控制的罕见遗传病研究的实用性。该队列将允许在 NF1 中实现完全表型表达后分析疾病和肿瘤异质性，并可能作为其他因招募不良而苦苦挣扎的罕见疾病的设计示例。

There is a burgeoning interest in therapeutic development for cutaneous neurofibromas (cNFs), a major cause of morbidity in persons with neurofibromatosis type 1 (NF1). To determine meaningful clinical trial outcomes, deeper understanding is needed regarding how cNFs are associated with quality of life (QoL). However, this understanding has been hampered by challenges in recruiting participants with this rare genetic disease.To develop a large, crowdsourced validated registry of persons with NF1 and determine the association of specific cNF features with QoL, pain, and itch.From May 2021 to December 2023, a decentralized platform was developed and recruited persons 40 years or older with NF1 and at least 1 cNF from 49 states and 12 countries, who provided clinical survey data, detailed photographs, and genetic sequencing data. Photographs from 583 participants were scored on 12 features of cNFs, including general severity, number, size, facial severity, color, and subtypes.cNF features derived from participant-supplied photographs.Total Skindex scores and subdomain scores (symptoms, emotion, function, pain, and itch).Of 583 participants, 384 (65.9%) were female, and the mean (range) age was 51.7 (40.0-83.0) years. Female sex, general severity, number, size, and facial severity of cNFs were negatively associated with QoL, as demonstrated by increased total Skindex scores. QoL had the largest association with the number of cNFs and presence of facial cNFs. Increasing number of cNFs was associated with worse QoL, and even individuals with a low cNF burden (<10 total cNFs) experienced a decrease in QoL.The results of this study suggest that reducing cNF number, particularly on the face, may be associated with improved QoL in individuals with NF1. In addition, early intervention before the development of numerous tumors may lead to the highest benefit in QoL. These data potentially provide insight into which individuals and cNF tumors may benefit most from therapy and highlights the utility of a completely decentralized, photograph-validated and age-controlled study for rare genetic disease. This cohort will allow analysis of disease and tumor heterogeneity after full phenotypic expression is achieved in NF1 and potentially serves as an example in its design for other rare diseases that struggle from poor recruitment.