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.

Sotos syndrome is a rare overgrowth-intellectual disability(OGID) disorder typically associated with developmental delay that stabilizes or improves with early intervention. We report a 17-month-old boy with classic clinical features of Sotos syndrome who presented with severe speech and motor delay. Whole-exome sequencing(WES) revealed a novel de novo nonsense pathogenic variant in NSD1:c.3910 C > T (p.Gln1304Ter), which is predicted to truncate multiple functional domains, including the SET(Su(var)3-9, Enhancer-of-zeste, and Trithorax) catalytic domain. Despite early and continuous rehabilitation, his developmental quotient(DQ) decreased from 45.8 at 17 months to 39.9 at 28 months, indicating slow and limited developmental progress over time. Brain MRI (magnetic resonance imaging) revealed corpus callosum abnormalities and reduced white matter volume. This is the first report of Sotos syndrome caused by the NSD1:c.3910 C > T (p.Gln1304Ter) pathogenic variant. Beyond expanding the spectrum of pathogenic variants, this case highlights a relatively severe neurodevelopmental profile with persistently limited progress, underscoring the importance of early genetic diagnosis, sustained multidisciplinary rehabilitation, and long-term follow-up to optimize outcomes in affected children.

Background: WITKOS is a rare neurodevelopmental disorder caused by heterozygous loss-of-function variants in the 15q24.1 - q24.2 region, includeing switch-insensitive 3 transcription regulator family member A (SIN3 A). Its incidence rate is extremely low. According to the current limited global data statistics, only a few cases occur per million population. Most cases concentrate in childhood and adolescence. During this stage, the rapid physiological changes of the body seem to be closely related to the triggering of the disease. Its characteristics include unique facial features, intellectual and motor developmental delay, and short stature. This paper reports a case of WITKOS in a 4-month-old infant caused by large-fragment copy number variation in the 15q24.1 - q24.2 region of the chromosome that encompasses the SIN3 A gene. Gene mutations lead to abnormal functions of key proteins, which subsequently disrupt the normal development and operation of multiple body systems., By summarizing its gene phenotype characteristics, it provides diagnostic and treatment ideas for clinicians to screen for developmentally deviated young children. It is expected to provide more effective treatment options for WITKOS to improve the prognosis of patients. Case presentation: This infant was diagnosed with WITKOS at 4 months of age. Subsequently, the manifestations included a wide forehead, a low nasal bridge, low-set ears, growth and intellectual developmental delay, low muscle tone in the limbs, and feeding difficulties. After early rehabilitation training, the language and motor abilities of this infant have been effectively improved, and currently, the infant can walk and run independently and can say short sentences independently. Conclusions: For children with WITKOS, early diagnosis of the clinical symptoms they exhibit and rehabilitation intervention should be carried out, which can effectively improve the quality of life of the children. This report is the first case of WITKOS caused by a large - fragment deletion, further enriching the case data of WITKOS and highlighting the necessity of strengthening clinical management and monitoring.