Genetic Variability in Child Growth Among South American Populations: A Perspective Integrating Population Genetics, Growth Standards, and Precision Growth Medicine

Child growth in South America results from a complex interplay of genetic, environmental, and socioeconomic factors. The region's high ancestral diversity-stemming from Native American, European, and African admixture-shapes growth patterns in ways not fully captured by international standard curves such as World Health Organization (WHO) charts, which are primarily based on European population. This mismatch may cause misclassification, especially among Native American and other underrepresented groups, and reduce the effectiveness of interventions like growth hormone (GH) therapy. Evidence from national surveys, cohort studies, and genetic analyses reveals persistent ethnic and socioeconomic disparities, with Native American children showing higher stunting prevalence even after adjusting for wealth and residence. Differences between WHO and national growth curves further contribute to inconsistent prevalence estimates due to methodological and contextual variants. Regional genomic studies, although limited, have identified population-specific variants, such as <i>FBN1</i> (E1297G) in Peru, and modulators of GH therapy response, including <i>GHR</i> exon 3 deletion, <i>ACAN</i>, and <i>NPR2</i>, highlighting the role of genetic background, treatment timing, and adherence in height outcomes. These findings underscore the need to move toward precision growth medicine, integrating anthropometry, genetic, environmental, and socioeconomic data to design population-specific growth references, optimize pharmacogenetic approaches, and reduce inequities in pediatric growth care.