Case Report: Differential Outcomes Associated with the Same Pathogenic Variant: Long-Term Follow-Up of a CHARGE Syndrome Case with a Nonsense Mutation C.6292c>t in the CHD Gene

BackgroundCHARGE syndrome (OMIM #214800) is a rare autosomal dominant multisystem disorder, most commonly attributable to de novo heterozygous loss-of-function pathogenic variants in the CHD7 gene. Pathogenic Pathogenic variants of CHD7 are distributed throughout the entire coding region, with nonsense and frameshift pathogenic variants predominating, and the vast majority constitute private mutations. Owing to its broad phenotypic spectrum and marked variability in expressivity, early diagnosis remains challenging. This article presents the long-term follow-up data of a female patient with genetically confirmed CHARGE syndrome, with particular emphasis on her clinical trajectory and outcomes achieved through multidisciplinary management.Case presentationThe patient was a full-term female born via spontaneous vaginal delivery in 2017, presenting with respiratory distress and feeding difficulties immediately after birth. Comprehensive evaluation revealed multisystem abnormalities involving the respiratory, cardiovascular, neurological, and sensory systems. Trio-based whole-exome sequencing identified a de novo heterozygous nonsense pathogenic variant, c.6292(EXON31)C>T (p.Arg2098*), in the CHD7 gene. Literature review indicated that this pathogenic variant had been previously reported in cases that all resulted in infantile death. In contrast, our patient, following active multidisciplinary management, achieved significant improvement in multiple organ functions and survived to school age, where she now adapts well to a special education school environment. This case provides the first evidence that this pathogenic variant is compatible with a favorable long-term outcome, highlighting substantial phenotypic heterogeneity and prognostic diversity even among individuals carrying an identical genetic alteration.ConclusionThis case highlights the critical importance of early genetic diagnosis and coordinated multidisciplinary management in CHARGE syndrome. By presenting divergent outcomes associated with the same pathogenic variant, our findings enrich the clinical evidence on CHD7 genotype–phenotype correlations. Even with severe neonatal multisystem involvement, proactive and individualized management can achieve favorable long-term outcomes.