背景：结节性硬化症（TSC）是一种多系统神经皮肤综合征，具有不同的表型。TSC诊断标准的最新更新重申了定义的遗传诊断标准，即发现TSC1或TSC2基因中的致病性DNA改变。它还稍微修改了明确的临床诊断标准。婴儿期与TSC相关的皮肤病变是重要的临床体征，可以选择可能具有TSC的个体进行更紧密的临床随访和基因测试。
目的：提高对更新的TSC诊断标准的认识；评估TSC患者皮肤病变的频率以及首次皮肤病学表现；并将这些发现与TSC1或TSC2突变相关联。
方法：观察性横断面研究。回顾性收集了来自巴西大学医院的37名TSC患者的临床和遗传数据。对有皮肤体征的患者进行检查和前瞻性评估，为期12个月。
结果：最早的皮肤病变是色素减少型黄斑，与血管纤维瘤一起是最常见的皮肤病学病变。TSC2和TSC1基因之间的总致病性DNA改变比例为8：1。TSC2致病性变异体的频率在指甲纤维瘤的存在下增加10倍。
结论：TSC1致病变异患者样本少，数量有限。
结论：临床医生应了解TSC更新的诊断标准。患者需要由多学科小组进行随访并进行相应的治疗。皮肤病变的早期检测对于TSC诊断很重要。描述了TSC2基因致病性改变与指甲纤维瘤之间的显着关联。
BACKGROUND: Tuberous sclerosis complex (TSC) is a multisystem neurocutaneous syndrome with variable phenotypes. Recent updates of TSC diagnostic criteria reaffirmed the defined genetic diagnostic criterion as the finding of a pathogenic DNA alteration in either TSC1 or TSC2 genes. It also slightly modified definite clinical diagnostic criteria. TSC-associated skin lesions in infancy are important clinical signs to select individuals with possible TSC for a closer clinical follow-up and genetic testing.
OBJECTIVE: To raise awareness of the updated TSC diagnosis criteria; to assess the frequency of skin lesions in TSC patients as well as the first dermatological presentation; and to associate the findings with either TSC1 or TSC2 mutations.
METHODS: Observational cross-sectional study. Clinical and genetic data were retrospectively collected from 37 TSC patients from a Brazilian University Hospital. Patients with skin signs were examined and prospectively assessed for 12 months.
RESULTS: The earliest cutaneous lesions were hypomelanotic macules, which together with angiofibromas were the most frequent dermatological lesions. The total pathogenic DNA alteration ratio between TSC2 and TSC1 genes was 8:1. The frequency of a TSC2 pathogenic variant was 10-fold greater in the presence of ungual fibromas.
CONCLUSIONS: Small sample and a limited number of patients with TSC1 pathogenic variants.
CONCLUSIONS: Clinicians should be knowledgeable about TSC updated diagnostic criteria. Patients need to be followed up by a multidisciplinary team and treated accordingly. Early detection of cutaneous lesions is important for TSC diagnosis. A significant association between TSC2 gene pathogenic alterations and ungual fibromas is described.
