Asian Journal of Pediatric Research

Rare childhood short stature disorders such as Achondroplasia, Hypochondroplasia, ACAN syndrome, and Noonan Syndrome are primarily caused by specific genetic mutations that disrupt normal bone growth and development. Advances in molecular diagnostics have improved early detection, while emerging gene therapy approaches—including CRISPR-Cas9—offer promising future strategies to target the underlying genetic defects. The review aims to focus on rare genetically determined dwarfism syndromes, including conditions such as achondroplasia, hypochondroplasia, ACAN syndrome, and Noonan syndrome, with a focus on their underlying genetic causes, clinical features, and diagnostic approaches. The present review was conducted using secondary sources derived from existing academic literature, including peer-reviewed journal articles, books, and conference proceedings. Achondroplasia, the most common form of dwarfism, and hypochondroplasia are primarily caused by activating mutations in the FGFR3 gene, leading to impaired endochondral ossification. In contrast, ACAN mutations affect cartilage structure and growth plate function, while Noonan syndrome involves mutations in genes of the RAS/MAPK signaling pathway, such as PTPN11. Gene therapy, including genome editing technologies such as CRISPR-Cas9, offer a prospective avenue for causal treatment by targeting the underlying genetic defects. Early detection through advanced genetic screening, potentially even prenatally, may further enhance therapeutic outcomes. This review highlights the growing potential of gene-based interventions while emphasizing the need for continued research to translate these approaches into safe and effective clinical applications.