Noonan Syndrome Type 5 Diagnosed by Next-Generation Sequencing: A Report of a Rare Pediatric Case
Abstract
Noonan syndrome (NS) is a genetically heterogeneous RASopathy characterized by distinctive facial features, growth impairment, developmental delay, and congenital heart disease. Variants in the RAF1 gene are strongly associated with hypertrophic cardiomyopathy (HCM). We report the case of a seven-year-old girl presenting with HCM, growth retardation, developmental delay, and characteristic dysmorphic features. Clinical suspicion of NS was raised during infancy. Initial investigations, including urinary glycosaminoglycan analysis and targeted molecular testing of the PTPN11 gene, were negative. Owing to persistent clinical suspicion, next-generation sequencing (NGS) was subsequently performed and identified a heterozygous pathogenic RAF1 variant, c.770C>T (p.Ser257Leu), establishing the diagnosis of NS type 5. This case highlights the importance of expanded molecular testing, particularly NGS, in patients with suspected RASopathies and reinforces the association between the RAF1 p.Ser257Leu variant and HCM.
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