Novel variants in and phenotype update in patients with Weiss-Kruszka syndrome: a case series.

BACKGROUND

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.

CASE DESCRIPTION

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.

CONCLUSIONS

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.