PDF(Pubmed)
Abstract：
Skin findings can be critical to determining whether a patient with lymphangioleiomyomatosis (LAM), a progressive pulmonary disease that predominantly affects adult women, has sporadic LAM or LAM in association with tuberous sclerosis complex (TSC). Three individuals with LAM underwent evaluation for TSC-associated mucocutaneous and internal findings. We used our previously published algorithm to confirm the clinical suspicion for mosaicism and guide the selection of tissue specimens and genetic workup. Next-generation sequencing of cutaneous findings was used to confirm clinical suspicion for mosaic TSC in individuals with LAM. Two individuals previously thought to have sporadic LAM were diagnosed with mosaic TSC-associated LAM upon next-generation sequencing of unilateral angiofibromas in one and an unusual cutaneous hamartoma in the other. A third individual, diagnosed with TSC in childhood, was found to have a mosaic pathogenic variant in TSC2 in cutaneous tissue from a digit with macrodactyly. Accurate diagnosis of mosaic TSC-associated LAM may require enhanced genetic testing and is important because of the implications regarding surveillance, prognosis, and risk of transmission to offspring.
摘要：
皮肤发现对于确定患者是否患有淋巴管平滑肌瘤病（LAM）至关重要。一种主要影响成年女性的进行性肺部疾病，有散发性LAM或与结节性硬化症（TSC）相关的LAM。三名LAM患者接受了TSC相关的粘膜皮肤和内部发现的评估。我们使用先前发布的算法来确认临床上对镶嵌性的怀疑，并指导组织标本的选择和遗传检查。皮肤发现的下一代测序用于确认LAM患者对马赛克TSC的临床怀疑。先前被认为是散发性LAM的两个人在对一个单侧血管纤维瘤和另一个异常皮肤错构瘤进行下一代测序后被诊断出患有与TSC相关的马赛克LAM。第三个人，在儿童时期被诊断为TSC，被发现在皮肤组织中的TSC2中具有马赛克致病变异，该变异来自大指。与马赛克TSC相关的LAM的准确诊断可能需要加强基因检测，并且由于对监测的影响而很重要。预后,和传播给后代的风险。
