Dual Diagnosis of Fragile X Syndrome and DEPDC5-Related Disorder Emphasizes DEPDC5's Role Beyond Familial Epilepsy: A Case Report and Literature Review.

Case Reports in Genetics Pub Date : 2025-04-02 eCollection Date: 2025-01-01 DOI:10.1155/crig/4501466
Rory Edwards, Grace Murphy, Joshua W Owens, Craig Erickson, Robert Hopkin, Amelle Shillington
{"title":"Dual Diagnosis of Fragile X Syndrome and DEPDC5-Related Disorder Emphasizes DEPDC5's Role Beyond Familial Epilepsy: A Case Report and Literature Review.","authors":"Rory Edwards, Grace Murphy, Joshua W Owens, Craig Erickson, Robert Hopkin, Amelle Shillington","doi":"10.1155/crig/4501466","DOIUrl":null,"url":null,"abstract":"<p><p>Dep domain-containing Protein 5 (DEPDC5), encoded by the gene DEPDC5, regulates the cell cycle by inhibiting the mTORC1 pathway in response to amino acid deficiency. Loss of function DEPDC5 variants are recognized to present as focal familial epilepsy; however, associations with comorbid brain malformations and neurodevelopmental disorders have also been reported. mTOR inhibitors were found to benefit DEPDC5-knockout mice. Fragile X syndrome (FXS) is an X-linked neurodevelopmental disorder caused by loss of function of FMR1, and females are expected to have milder neurodevelopmental presentations than males. The reported individual is a 17-year-old female diagnosed with FXS at 1 year of age, but the severity of her neuropsychiatric symptoms prompted further genetic testing at age 14, revealing a likely pathogenic c.4307_4310del DEPDC5 variant. Following this diagnosis, she was started on the mTOR inhibitor sirolimus without significant clinical response. She has never been diagnosed with epilepsy; however, her DEPDC5 and FXS dual diagnosis was thought explanatory for her presentation. A review of 213 previously reported individuals with DEPDC5-related disorder demonstrated that 15.2% of individuals do not have epilepsy, 24.3% have intellectual disability, and 33.8% have brain malformations. Her lack of response to sirolimus may represent the presence of a critical treatment window for mTOR inhibitors in neurodevelopmental disorders.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2025 ","pages":"4501466"},"PeriodicalIF":0.0000,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11981699/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Case Reports in Genetics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1155/crig/4501466","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Dep domain-containing Protein 5 (DEPDC5), encoded by the gene DEPDC5, regulates the cell cycle by inhibiting the mTORC1 pathway in response to amino acid deficiency. Loss of function DEPDC5 variants are recognized to present as focal familial epilepsy; however, associations with comorbid brain malformations and neurodevelopmental disorders have also been reported. mTOR inhibitors were found to benefit DEPDC5-knockout mice. Fragile X syndrome (FXS) is an X-linked neurodevelopmental disorder caused by loss of function of FMR1, and females are expected to have milder neurodevelopmental presentations than males. The reported individual is a 17-year-old female diagnosed with FXS at 1 year of age, but the severity of her neuropsychiatric symptoms prompted further genetic testing at age 14, revealing a likely pathogenic c.4307_4310del DEPDC5 variant. Following this diagnosis, she was started on the mTOR inhibitor sirolimus without significant clinical response. She has never been diagnosed with epilepsy; however, her DEPDC5 and FXS dual diagnosis was thought explanatory for her presentation. A review of 213 previously reported individuals with DEPDC5-related disorder demonstrated that 15.2% of individuals do not have epilepsy, 24.3% have intellectual disability, and 33.8% have brain malformations. Her lack of response to sirolimus may represent the presence of a critical treatment window for mTOR inhibitors in neurodevelopmental disorders.

脆性X综合征和DEPDC5相关疾病的双重诊断强调了DEPDC5在家族性癫痫之外的作用:1例报告和文献复习
Dep结构域蛋白5 (DEPDC5)由DEPDC5基因编码,在氨基酸缺乏时通过抑制mTORC1通路调节细胞周期。功能丧失的DEPDC5变异被认为是局灶性家族性癫痫;然而,与共病性脑畸形和神经发育障碍的关联也有报道。发现mTOR抑制剂对depdc5敲除小鼠有益。脆性X综合征(FXS)是一种由FMR1功能丧失引起的X连锁神经发育障碍,女性的神经发育表现预计比男性轻。报告的个体是一名17岁的女性,在1岁时被诊断患有FXS,但她的神经精神症状的严重程度促使她在14岁时进行了进一步的基因检测,揭示了可能的致病性c.4307_4310del DEPDC5变体。在此诊断后,她开始使用mTOR抑制剂西罗莫司,但没有明显的临床反应。她从未被诊断患有癫痫;然而,她的DEPDC5和FXS双重诊断被认为可以解释她的表现。对213例先前报道的depdc5相关疾病患者的回顾表明,15.2%的患者没有癫痫,24.3%的患者有智力残疾,33.8%的患者有脑畸形。她对西罗莫司缺乏反应可能代表mTOR抑制剂在神经发育障碍中的关键治疗窗口的存在。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
21
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信