<italic style="font-style: italic">CNKSR2</italic>基因变异所致Houge型X连锁综合征型智力障碍7例并文献复习

段浩林; 熊娟; 庞楠; 尹飞; 彭镜

doi:10.11817/j.issn.1672-7347.2026.240640

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CNKSR2基因变异所致Houge型X连锁综合征型智力障碍7例并文献复习

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短篇论著 | 更新时间：2026-05-05

CNKSR2基因变异所致Houge型X连锁综合征型智力障碍7例并文献复习
CNKSR2 gene variants causing Houge type of X-linked syndromic intellectual developmental disorder: Seven cases and literature review
中南大学学报(医学版) 中南大学学报(医学版) 2026年51卷第2期页码：333-340
作者机构：

中南大学湘雅医院儿童医学中心，湖南省儿童智力障碍研究中心，湖南省儿童脑发育障碍性疾病临床医学研究中心，长沙 410008
作者简介：

段浩林，Email: 218102082@csu.edu.cn, ORCID: 0009-0008-9885-6953
彭镜，主任医师，Email: pengjing@csu.edu.cn, ORCID: 0000-0002-7752-6962
基金信息：

国家自然科学基金(82471488┫。This work was supported by the National Natural Science Foundation of China ┣82471488)
DOI：10.11817/j.issn.1672-7347.2026.240640
中图分类号：
CSTR：
收稿：2024-11-25，

纸质出版：2026-02-28
稿件说明：

段浩林, 熊娟, 庞楠, 尹飞, 彭镜. CNKSR2基因变异所致Houge型X连锁综合征型智力障碍7例并文献复习[J]. 中南大学学报(医学版), 2026, 51(2): 333-340.

DUAN Haolin, XIONG Juan, PANG Nan, YIN Fei, PENG Jing. CNKSR2 gene variants causing Houge type of X-linked syndromic intellectual developmental disorder: Seven cases and literature review[J]. Journal of Central South University. Medical Science, 2026, 51(2): 333-340.
段浩林, 熊娟, 庞楠, 尹飞, 彭镜. CNKSR2基因变异所致Houge型X连锁综合征型智力障碍7例并文献复习[J]. 中南大学学报(医学版), 2026, 51(2): 333-340. DOI：10.11817/j.issn.1672-7347.2026.240640.

DUAN Haolin, XIONG Juan, PANG Nan, YIN Fei, PENG Jing. CNKSR2 gene variants causing Houge type of X-linked syndromic intellectual developmental disorder: Seven cases and literature review[J]. Journal of Central South University. Medical Science, 2026, 51(2): 333-340. DOI：10.11817/j.issn.1672-7347.2026.240640.

摘要

目的

CNKSR2

基因变异导致的Houge型X连锁综合征型智力障碍(Houge type of X-linked syndromic intellectual developmental disorder，MRXSHG)较为罕见，患者常合并难治性癫痫，易出现睡眠期癫痫性电持续状态(electrical status epilepticus during sleep，ESES)，进而加重认知损害。本研究分析7例

CNKSR2

基因变异导致MRXSHG患者的临床资料，并结合文献回顾，旨在为临床上诊断此类患者提供参考。

方法

回顾性分析2020年6月至2025年11月在中南大学湘雅医院儿童医学中心诊治的7例经全外显子组测序确诊为

CNKSR2

基因突变患儿的临床资料，并回顾相关文献(15篇文献，包含42例患者)，共总结分析49例患者的资料。

结果

患者年龄范围为4月龄至62岁，男女比例为11.2꞉1。患者主要临床表现包括全面发育迟缓/智力障碍(100%，49/49)、癫痫(91.8%，45/49)、注意缺陷多动障碍(77.6%，38/49)、语言缺失(75.5%，37/49)、睡眠障碍(28.6%，14/49)。少数还伴有喂养困难(12.2%，6/49)、孤独症谱系障碍(10.2%，5/49)、肌张力改变(6.1%，3/49)、小头畸形(6.1%，3/49)及面部畸形(4.1%，2/49)。在有睡眠期脑电图资料的36例患者中，16例(44.4%)存在ESES。本中心的4例患者合并身材矮小和/或营养不良，在既往文献中未见报道。在已知癫痫转归的34例患者中，14例(41.2%)经丙戊酸钠、卡马西平或拉莫三嗪等治疗后发作控制；16例(47.1%)为难治性癫痫；其余4例(11.8%)未治疗、发作状态不明或仍在调整治疗方案。

结论

对于存在智力障碍、语言发育迟缓突出，尤其合并难治性癫痫及ESES的男性患者，需考虑

CNKSR2

基因变异所致MRXSHG的可能，建议通过遗传检测予以确诊，并提供优生优育指导。

Abstract

Objective

Houge type of X-linked syndromic intellectual developmental disorder (MRXSHG) caused by

CNKSR2

gene variants is a rare neurodevelopmental disorder. Patients commonly present with refractory epilepsy and are prone to developing electrical status epilepticus during sleep (ESES)

which may further aggravate cognitive impairment. This study analyzes 7 patients with

CNKSR2

gene variants causing MRXSHG

combined with a li

terature review

aiming to provide a reference for the clinical diagnosis of similar patients.

Methods

A retrospective analysis was conducted on the clinical data of 7 children diagnosed with

CNKSR2

gene mutations by whole‑exome sequencing at the Children’s Medical Center

Xiangya Hospital

Central South University

from June 2020 to November 2025. Combined with a literature review (15 publications involving 42 patients)

a total of 49 patients were summarized and analyzed.

Results

The reported age ranged from 4 months to 62 years

with a male-to-female ratio of 11.2꞉1. Major clinical manifestations included global developmental delay/intellectual disability (100%

49/49)

epilepsy (91.8%

45/49)

attention deficit hyperactivity disorder (77.6%

38/49)

absence of speech (75.5%

37/49)

and sleep disturbances (28.6%

14/49). Among 36 patients with available sleep electroencephalogram data

16 (44.4%) exhibited ESES. A minority of patients also presented with feeding difficulties (12.2%

6/49)

autism spectrum disorder (10.2%

5/49)

abnormal muscle tone (6.1%

3/49)

microcephaly (6.1%

3/49)

and facial dysmorphism (4.1%

2/49). Four patients from our center exhibited short stature and/or malnutrition

which have not been previously reported. Among 34 patients with known epilepsy outcomes

14 (41.2%) achieved seizure control with valproate

carbamazepine

or lamotrigine; 16 (47.1%) had refractory epilepsy; and 4 (11.8%) were untreated

had unclear seizure status

or were still undergoing treatment adjustment.

Conclusion

For male patients presenting with intellectual disability and prominent language delay

particularly those with refractory epilepsy and ESES

MRXSHG caused by

CNKSR2

variants should be considered. Genetic testing is essential for definitive diagnosis and for providing genetic counseling.

关键词

Keywords

references

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CNKSR2基因变异所致Houge型X连锁综合征型智力障碍7例并文献复习

CNKSR2 gene variants causing Houge type of X-linked syndromic intellectual developmental disorder: Seven cases and literature review

DOI：10.11817/j.issn.1672-7347.2026.240640

摘要

Abstract

关键词

Keywords

references