Hypotonia-ataxia-developmental delay syndrome caused by EBF3 variant in a child: a case report and literature review
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摘要: 分析2024年8月就诊于温州医科大学附属第一医院儿童神经内科的1例肌张力减退-共济失调-发育迟缓综合征(hypotonia-ataxia-developmental delay syndrome，HADDS)患儿的临床表型及遗传学病因，患儿为1岁2个月，因“发育迟缓半年余”就诊。临床表现为肌张力减退、全面发育迟缓、异常面部特征及共济失调等。家系全外显子组测序发现患儿EBF3基因存在c.1038C>A(p.Y346*)无义变异，Sanger测序验证父母均无此变异。经分析，依据美国医学遗传学与基因组学学会标准，该变异被判定为致病性。通过复习文献总结相关疾病临床表现与遗传学特征，该病例不仅扩展了EBF3变异所致HADDS的变异谱，还丰富了其临床表型，为该疾病研究提供了新的案例与依据。
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关键词:
- 肌张力减退-共济失调和发育迟缓综合征 /
- EBF3基因 /
- 全外显子测序 /
- 常染色体显性遗传
Abstract: This study analyzed the clinical phenotype and genetic etiology of a 14-month-old patient patient diagnosed with hypotonia-ataxia-developmental delay syndrome (HADDS) who was admitted to the Department of Pediatric Neurology at the First Affiliated Hospital of Wenzhou Medical University in August 2024. The patient presented with "developmental delay for over six months" as the chief complaint, exhibiting clinical manifestations including hypotonia, global developmental delay, characteristic facial features, and ataxia. Whole-exome sequencing of the family identified a nonsense variant c.1038C>A (p.Y346*) in the EBF3 gene of the proband, which was absent in both parents as confirmed by Sanger sequencing. According to the American College of Medical Genetics and Genomics standards, this variant was classified as pathogenic. Through literature review summarizing relevant disease manifestations and genetic characteristics, this case not only expands the variant spectrum of EBF3 -related HADDS but also enriches its clinical phenotype, providing new evidence and case reference for research on this disorder. -
图 1 EBF3变异所致肌张力减退-共济失调-发育迟缓综合征患儿头颅核磁共振成像
注：A为T2加权轴位扫描；B为T2加权矢状位扫描。小脑脑叶呈放射状分布，形似蒲公英外观。
Figure 1. Head magnetic resonance imaging of children with EBF3 mutation-related hypotonia ataxia and developmental delay syndrome
图 2 基因变异结果及致病性分析结果
注：红色箭头示突变位点。先证者EBF3存在c.1038C>A杂合突变，其父母未见相同变异。
Figure 2. Analysis results of genetic variations and pathogenicity
图 3 EBF3蛋白野生型和变异型的3D蛋白质结构
注：A为野生型整体结构图；B为突变型整体结构图。
Figure 3. The 3D protein structures of the wild-type and mutant forms of the protein
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