Abstract
BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is a genetic disorder characterized by various clinical features. The purpose of this study was to investigate the molecular diagnostic and clinical features of BWS in Chinese pediatric patients. METHODS: This retrospective study reviewed the clinical data of 24 pediatric patients diagnosed with BWS at the Guangzhou Women and Children's Medical Center, Guangzhou Medical University from 2014 to 2024. To assess genetic abnormalities, molecular analysis was performed using array comparative genomic hybridization (Array-CGH) as well as methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). RESULTS: With a range of fetal period to four years, the median age at diagnosis was nine months. Cardinal features were macroglossia (95.8%), lateralized overgrowth (54.2%), and omphalocele (25%). Suggestive features included transient hypoglycemia (20.8%), hepatomegaly or nephromegaly (8.3%), and facial port-wine stain or ear-lobe creases (8.3%). Molecular analysis revealed that 57.9% of patients had methylation abnormalities in the imprinting control region 2 (IC2), while 5.3% had abnormalities in imprinting control region 1 (IC1), and 36.8% diagnosed with uniparental disomy (UPD). One patient also exhibited a rare homozygous mutation in the DUOX2 gene and a heterozygous mutation in the LDLR gene. CONCLUSIONS: This study investigates the significance of early genetic testing in the clinical and molecular features of pediatric BWS demonstrating that MLPA exhibits its higher sensitivity and specificity for genetic testing in these patients. Furthermore, the findings identified a high prevalence of UPD in the southern Chinese population and highlighted the diagnostic role of chromosomal microarray analysis (CMA) in detecting UPD-related phenotypes in patients with BWS.