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伴 Rett 样表型的神经发育障碍。

Rett-like Phenotypes in -Related Neurodevelopmental Disorder.

机构信息

Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Department of Neurology, Division of Child Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA.

出版信息

Genes (Basel). 2023 May 26;14(6):1154. doi: 10.3390/genes14061154.

Abstract

Rett Syndrome (RTT) is a neurodevelopmental disorder with a prevalence of 1:10,000 to 15,000 females worldwide. Classic Rett Syndrome presents in early childhood with a period of developmental regression, loss of purposeful hand skills along with hand stereotypies, gait abnormalities, and loss of acquired speech. Atypical RTT is diagnosed when a child shows some but not all the phenotypes of classic RTT, along with additional supporting criteria. Over 95% of classic RTT cases are attributed to pathogenic variants in Methyl-CpG Binding Protein 2 (), though additional genes have been implicated in other RTT cases, particularly those with the atypical RTT clinical picture. Other genetic etiologies have emerged with similar clinical characteristics to RTT Syndrome. Our team has characterized -related neurodevelopmental disorder (RNDD) in 33 individuals associated with de novo pathogenic missense variants in the X-linked gene, characterized by developmental delay, intellectual disability, seizures, autistic-like features, and motor abnormalities. We sought to further characterize RTT clinical features in this group of individuals by using caregiver report. Twenty-six caregivers completed electronic surveys, with only 3 individuals having previously received an atypical RTT diagnosis, and no individuals with a typical RTT diagnosis. Caregivers reported a high number of behaviors and/or phenotypes consistent with RTT, including the major criteria of the syndrome, such as regression of developmental skills and abnormal gait. Based on the survey results, 12 individuals could meet the diagnostic clinical criteria for atypical RTT Syndrome. In summary, individuals with RNDD exhibit clinical characteristics that overlap with those of RTT, and therefore, RNDD, should be considered on the differential diagnosis list with this clinical picture.

摘要

雷特综合征(RTT)是一种神经发育障碍,全球范围内女性患病率为 1:10000 至 15000。经典 RTT 于儿童早期发病,经历一段发育倒退期,丧失目的性手部技能,出现手部刻板动作、步态异常和获得性言语丧失。当儿童表现出经典 RTT 的部分而非全部表型,且伴有其他支持标准时,可诊断为非典型 RTT。超过 95%的经典 RTT 病例归因于甲基化 CpG 结合蛋白 2()的致病性变异,尽管其他基因也与其他 RTT 病例相关,尤其是那些具有非典型 RTT 临床表现的病例。其他遗传病因也具有与 RTT 综合征相似的临床特征。我们的团队在 33 名个体中描述了与 X 连锁基因中的从头致病性错义变异相关的 -相关神经发育障碍(RNDD),这些个体的特征为发育迟缓、智力残疾、癫痫发作、类自闭症特征和运动异常。我们试图通过使用护理人员报告进一步描述这组个体的 RTT 临床特征。26 名护理人员完成了电子调查,仅有 3 名个体之前被诊断为非典型 RTT,没有个体被诊断为典型 RTT。护理人员报告了大量与 RTT 一致的行为和/或表型,包括该综合征的主要标准,如发育技能的倒退和异常步态。根据调查结果,有 12 名个体符合非典型 RTT 综合征的诊断临床标准。总之,RNDD 个体表现出与 RTT 重叠的临床特征,因此,应将 RNDD 纳入该临床表现的鉴别诊断清单。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4040/10298048/cac8f893cc05/genes-14-01154-g001.jpg

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