Department of Medical Genetics, Medical School and Clinical Centre, University of Pécs, H-7624 Pécs, Hungary.
Bethesda Children's Hospital, H-1146 Budapest, Hungary.
Int J Mol Sci. 2023 Aug 17;24(16):12886. doi: 10.3390/ijms241612886.
Tuberous sclerosis complex (TSC) is a multisystem disorder characterized by seizures, neuropsychiatric disorders, and tumors of the heart, brain, skin, lungs, and kidneys. We present a three-year follow-up of a patient with TSC-associated rhabdomyoma detected in utero. Genetic examination of the fetus and the parents revealed a de novo variant in the gene (c.3037delG, p.Asp1013IlefsTer3). Oral everolimus was initiated in the pregnant mother to regress the fetal tumor, which was successful. To the best of our knowledge, there is very little information regarding the use of everolimus therapy during pregnancy. West-syndrome was diagnosed when the proband was four months old. The symptoms were well-manageable, however temporarily. Therapy-resistant focal seizures were frequent. The patient had good vitals and was under regular cardiological control, showed a balanced circulation, and did not require any medication. Subependymal giant cell astrocytoma (SEGA) identified by regular neuroimaging examinations remained unchanged, which may be a consequence of early intrauterine treatment. Early detection of the pathogenic variant, followed by in utero administration of everolimus and early vigabatrin therapy, allowed the detection of a milder developmental delay of the proband. Our study emphasizes how early genetic testing and management of epilepsy are pivotal for proper neurodevelopmental impacts and therapeutic strategies.
结节性硬化症复合征（TSC）是一种多系统疾病，其特征为癫痫发作、神经精神障碍以及心脏、脑、皮肤、肺和肾脏的肿瘤。我们报告了一例在宫内发现的与 TSC 相关的横纹肌瘤患者的三年随访结果。对胎儿及其父母进行基因检查发现了一个新出现的 基因变异（c.3037delG，p.Asp1013IlefsTer3）。为了使胎儿肿瘤消退，给孕妇口服依维莫司，但我们所知，在怀孕期间使用依维莫司治疗的信息非常有限。当患儿四个月大时，被诊断为 West 综合征。症状虽然可以得到暂时控制，但仍很严重。频繁出现治疗抵抗性局灶性癫痫发作。患儿生命体征良好，定期接受心内科检查，循环稳定，无需用药。定期神经影像学检查发现的室管膜下巨细胞星形细胞瘤（SEGA）保持不变，这可能是宫内治疗的结果。早期发现致病性 变异，并在宫内给予依维莫司和早期加巴喷丁治疗，使得患儿的发育迟缓程度较轻。我们的研究强调了早期进行基因检测和癫痫管理对于适当的神经发育影响和治疗策略的重要性。
