Abstract
RATIONALE: Weaver syndrome is a rare congenital overgrowth disorder characterized by a wide spectrum of clinical manifestations that often overlap with other overgrowth syndromes. It is primarily caused by pathogenic variants in the Enhancer of Zeste Homolog 2 (EZH2) gene on chromosome 7q36.1. Globally, fewer than 70 cases have been reported, with only a few documented in the Chinese population. PATIENT CONCERNS: We report a 13-day-old Chinese male infant, born with macrosomia (birth weight: 5.04 kg), who was admitted for persistent neonatal jaundice. Physical examination and subsequent follow-up revealed accelerated postnatal growth and characteristic craniofacial features, including a broad forehead, hypertelorism, epicanthal folds, a flat nasal bridge, and low-set ears. His length, weight, and head circumference consistently plotted above the 97th percentile for his age. Additional findings included large hands and feet. DIAGNOSES: The child was ultimately diagnosed with "Weaver syndrome." INTERVENTIONS: DNA nanoballs were prepared with a universal sequencing reaction kit and subjected to paired-end sequencing on the MGISEQ-2000 platform. The resulting reads were aligned to the human reference genome hg19 (GRCh37). After removing PCR duplicates, single nucleotide polymorphisms and insertions/deletions were identified and annotated against established variant databases. The potential pathogenicity of the identified variants and their structural impact on the protein were evaluated using computational prediction tools. This analysis revealed a missense variant in the EZH2 gene (NM_004456.4:c.2050C>T) in the proband, resulting in an arginine-to-cysteine substitution at codon 684 (p.Arg684Cys). In accordance with American College of Medical Genetics and Genomics guidelines, this variant was classified as pathogenic. Subsequent Sanger sequencing confirmed it as a de novo mutation. OUTCOMES: The patient received multidisciplinary guidance for neurodevelopmental, speech, and behavioral therapy. He remains under regular follow-up to monitor his growth and development. LESSONS: This report documents a new case of Weaver syndrome in China harboring a de novo EZH2 mutation, expanding the genotypic and phenotypic spectrum of this disorder in the Chinese population. Our findings underscore the critical role of genetic testing in achieving a definitive diagnosis for rare overgrowth syndromes, facilitating early intervention and appropriate management.