Huai Wan, Li Juan, Li Xin, Ding Yu, Yu Tingting, Zhang Hao, Wang Xiumin, Yao Ruen
Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Endocrinology and Metabolism, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Transl Pediatr. 2025 Aug 31;14(8):1991-2000. doi: 10.21037/tp-2025-274. Epub 2025 Aug 20.
Weiss-Kruszka syndrome (WSKA) is a neurodevelopmental disorder caused by loss-of-function variants in , a zinc-finger transcription factor critical for embryonic morphogenesis. Characterized by intellectual disability, facial dysmorphism, muscle tone abnormalities, and congenital malformations, WSKA exhibits significant phenotypic heterogeneity. Despite over 40 cases reported globally, existing studies rarely report the clinical manifestations of this disease in Chinese patients.
Six patients harboring pathogenic variants were included and clinically evaluated at Shanghai Children's Medical Center. Comprehensive phenotyping included detailed dysmorphology assessments, neurodevelopmental testing, and targeted organ system evaluations. Whole-exome sequencing (WES) with Sanger confirmation identified pathogenic variants. Additionally, phenotypic data from prior published cases were systematically reviewed. WES confirmed the diagnosis of WSKA in six patients from five pedigrees, revealing five novel variants. Phenotypic information in our Chinese patient cohort revealed similar neurodevelopmental abnormalities and dysmorphic facial features. Other clinical features, including growth hormone deficiency, limb anomalies, and abnormal gonadal development, were also observed within different individuals in our cohort, suggesting phenotypic variability and heterogeneity among different ethnic origins.
Identifying novel pathogenic variants in and compiling a comprehensive clinical phenotype spectrum of patients could provide crucial information for the precise diagnosis and treatment of WSKA in Han Chinese individuals. Our findings underscore the necessity of ethnicity-specific diagnostic criteria.
魏斯-克鲁什卡综合征（WSKA）是一种神经发育障碍，由对胚胎形态发生至关重要的锌指转录因子功能丧失变异引起。WSKA以智力残疾、面部畸形、肌张力异常和先天性畸形为特征，表现出显著的表型异质性。尽管全球已报道40多例病例，但现有研究很少报道中国患者的这种疾病临床表现。
纳入6例携带致病性变异的患者，并在上海儿童医学中心进行临床评估。综合表型分析包括详细的畸形评估、神经发育测试和靶向器官系统评估。经桑格确认的全外显子测序（WES）确定了致病性变异。此外，还系统回顾了先前发表病例的表型数据。WES确诊了来自五个家系的6例患者患有WSKA，发现了5个新的变异。我们中国患者队列中的表型信息显示出相似的神经发育异常和面部畸形特征。我们队列中的不同个体还观察到其他临床特征，包括生长激素缺乏、肢体异常和性腺发育异常，这表明不同种族之间存在表型变异性和异质性。
识别中的新致病性变异并汇编患者的综合临床表型谱可为汉族个体WSKA的精确诊断和治疗提供关键信息。我们的研究结果强调了特定种族诊断标准的必要性。
