Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Clin Dermatol. 2022 Jul-Aug;40(4):374-382. doi: 10.1016/j.clindermatol.2022.02.010. Epub 2022 Mar 4.
Neurofibromatosis (NF) and tuberous sclerosis complex (TSC) are the two most common neurocutaneous disorders, both transmitted as autosomal dominant or, in the case of NF, also as a mosaic condition. The causative genetic mutations in these neurocutaneous disorders can lead to benign skin changes or uninhibited growth and proliferation in multiple organ systems due to the loss of tumor suppression in mitogen-activated protein kinase and mammalian target of rapamycin signaling pathways. Common clinical features in NF include pigmented lesions, known as café au lait patches, neurofibromas, intertriginous freckles (Crowe's sign), and benign fibrous growths, such as hamartomas in multiple organ systems. Common clinical features in TSC include hypopigmented macules, known as ash leaf spots, in addition to neurologic sequelae, such as autism, seizures, and developmental delays. Advances in genetic sequencing technologies have allowed an exponential expansion in the understanding of NF and TSC. Consensus criteria have been established for both diagnoses that can be confirmed in most cases through gene testing. Once diagnosed, the clinical and diagnostic value of disease-specific surveillance include early identification of benign and malignant tumors. Genetic counseling is important for informed reproductive decision-making for patients and at-risk family members. The improvement in understanding of pathways of pathogenic disease development and oncogenesis in both conditions have produced a new series of therapeutic options that can be used to control seizures and tumor growth. Tremendous advances in life expectancy and quality of life are now a reality due to early introduction of seizure control and novel medications. While we lack cures, early institution of interventions, such as seizure control in tuberous sclerosis, appears to be disease-modifying and holds immense promise to offer patients better lives.
神经纤维瘤病 (NF) 和结节性硬化症 (TSC) 是两种最常见的神经皮肤疾病，均为常染色体显性遗传，或在 NF 的情况下，也为嵌合体条件。这些神经皮肤疾病中的致病基因突变可导致良性皮肤改变或由于丝裂原活化蛋白激酶和哺乳动物雷帕霉素靶蛋白信号通路中的肿瘤抑制丧失，导致多器官系统不受抑制的生长和增殖。NF 的常见临床特征包括色素沉着病变，称为咖啡牛奶斑，神经纤维瘤，皱褶间雀斑（Crow 的征），以及多器官系统中的良性纤维性生长，如错构瘤。TSC 的常见临床特征除了神经后遗症，如自闭症、癫痫和发育迟缓外，还包括色素减退性斑，称为灰烬叶斑。遗传测序技术的进步使我们对 NF 和 TSC 的理解呈指数级增长。这两种疾病都建立了共识标准，大多数情况下可以通过基因测试来确认。一旦诊断，疾病特异性监测的临床和诊断价值包括早期识别良性和恶性肿瘤。遗传咨询对于患者和高危家庭成员的知情生殖决策很重要。对两种疾病的致病疾病发展和致癌途径的理解的提高产生了一系列新的治疗选择，可用于控制癫痫发作和肿瘤生长。由于早期引入癫痫控制和新型药物，现在预期寿命和生活质量都得到了显著提高。虽然我们缺乏治愈方法，但早期干预，如结节性硬化症中的癫痫控制，似乎可以改变疾病进程，并为患者提供更好的生活带来巨大希望。
