结节性硬化症 (TSC) 是一种多系统疾病，由 mTOR 通路抑制剂基因 TSC1 和 TSC2 的失活变异引起。 TSC 患者易患多个器官良性肿瘤以及 TSC 相关神经精神疾病 (TAND) 和癫痫。与 TSC1 相比，TSC2 的致病变异通常与更严重的表型相关； TSC2 R905Q 变体已被证明是一个例外，据报道患者出现异常轻微的 TSC 特征，这些特征可能未被检测到。我们研究了一名 13 岁个体和三名患有 TSC2 c 的家庭成员的 TSC 表型。 .2714G>A (R905Q) 致病性变异。1 号患者出现严重的医学难治性癫痫，无结节或室管膜下结节，虚拟检查中仅漏掉了轻微的 TSC 皮肤病学特征。她的母亲和姨妈（患者 2 和患者 3 在 50 岁后诊断）表现出轻度表型，具有皮肤病学特征和 TAND。她的叔叔（患者 4，47 岁被诊断出）表现出最严重的表型，表现为智力障碍、难治性癫痫、强迫症、创伤后应激障碍和精神病。这项研究扩展了可能的表型谱TSC2 R905Q 变体，证明与严重癫痫有关，但没有相关的神经放射学特征。本演讲强调了 TSC 中隐匿性局灶性皮质发育不良的可能性，并强调了对严重癫痫患者进行基因检测的重要性。此外，随后对其他家庭成员进行了成年晚期诊断，以便进行适当的 TSC 监测。Crown 版权所有 © 2024。由 Elsevier Inc 出版。保留所有权利。

Tuberous sclerosis complex (TSC) is a multisystemic disorder caused by inactivating variants in the mTOR pathway inhibitor genes TSC1 and TSC2. Individuals with TSC are predisposed to benign tumors in multiple organs as well as TSC-associated neuropsychiatric disorders (TAND) and epilepsy. Pathogenic variants in TSC2 are typically associated with a more severe phenotype compared with TSC1; the TSC2 R905Q variant has been shown to be an exception, where patients have been reported to present with unusually mild TSC features that may be undetected.We studied the TSC phenotype of a 13-year-old individual and three family members with a TSC2 c.2714G>A (R905Q) pathogenic variant.Patient 1 presented with severe medically refractory epilepsy without tubers or subependymal nodules and only mild dermatologic features of TSC missed on virtual examinations. Her mother and maternal aunt (Patients 2 and 3-diagnosed after age 50 years) presented with a mild phenotype, with dermatologic features and TAND. Her maternal uncle (Patient 4-diagnosed at age 47 years) displayed the most severe phenotype, presenting with intellectual disability, medically refractory epilepsy, obsessive-compulsive disorder, post-traumatic stress disorder, and psychosis.This study expands the possible phenotypic spectrum of TSC2 R905Q variant, demonstrating an association with severe epilepsy without associated neuroradiological stigmata. This presentation highlights the possibility of occult focal cortical dysplasia in TSC and emphasizes the importance of genetic testing in individuals with severe epilepsy. Moreover, a late adult diagnosis was subsequently made in other family members allowing for appropriate TSC surveillance to occur.Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.