Noonan Syndrome: Relation of Genotype to Cardiovascular Phenotype-A Multi-Center Retrospective Study

• Published in: Genes 2024-11, Vol.15 (11), p.1463
• Main Authors: Ilic, Nikola, Krasic, Stasa, Maric, Nina, Gasic, Vladimir, Krstic, Jovana, Cvetkovic, Dimitrije, Miljkovic, Vesna, Zec, Boris, Maver, Ales, Vukomanovic, Vladislav, Sarajlija, Adrijan
• Format: Article
• Language: English
• Subjects: Adolescent; Analysis; Cardiomyopathy; Cardiomyopathy, Hypertrophic - epidemiology; Cardiomyopathy, Hypertrophic - genetics; Cardiomyopathy, Hypertrophic - pathology; Child; Child, Preschool; Children; Congenital heart disease; Coronary artery disease; Development and progression; Exome Sequencing; Female; Gene mutations; Genetic aspects; Genetic disorders; Genetic engineering; Genomes; Genotype; Genotype & phenotype; Genotypes; Health aspects; Heart diseases; Heart failure; Humans; Infant; Male; Medical records; Medical research; Medicine, Experimental; Mitochondrial DNA; Mutation; Noonan syndrome; Noonan Syndrome - epidemiology; Noonan Syndrome - genetics; Noonan Syndrome - pathology; Noonan's syndrome; Pathogenesis; Patients; Pediatric clinics; Pediatrics; Phenotype; Phenotypes; Prevalence studies (Epidemiology); Protein Tyrosine Phosphatase, Non-Receptor Type 11 - genetics; Proto-Oncogene Proteins c-raf - genetics; Pulmonary Valve Stenosis - epidemiology; Pulmonary Valve Stenosis - genetics; Pulmonary Valve Stenosis - pathology; Retrospective Studies; Rheumatic heart disease; Software; Stenosis; Whole genome sequencing
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes15111463

Noonan syndrome (NS) is a congenital genetic disorder with a prevalence of 1 in 1000 to 2500 live births, and is characterized by distinctive facial features, short stature, chest deformities, and congenital heart disease. This study aims to evaluate the prevalence of specific genetic mutations and their impact on cardiovascular and other outcomes in NS. We conducted a retrospective clinical study of 25 pediatric patients diagnosed with NS at two institutions: The Mother and Child Health Care Institute of Serbia and the Clinic for Children Diseases, University Clinical Center of the Republic of Srpska. Patients underwent whole-exome sequencing (WES) to identify genetic mutations. Clinical data, including cardiovascular manifestations, psychomotor development, and stature, were analyzed in relation to mutation types. The cohort comprised 60% male and 40% female patients, with a median age at diagnosis of 7.2 years. Cardiovascular abnormalities were present in 88% of patients. Mutations in were most commonly associated with pulmonary valve stenosis (PVS), while mutations were prevalent in patients with hypertrophic cardiomyopathy (HCM). No significant association was found between cardiac disease and delayed psychomotor development ( = 0.755), even though the likelihood ratio showed significance in that regard ( = 0.018). Short stature was observed in 48% of patients but was not significantly correlated with genetic type of disease, presence of cardiac disease, or developmental delay. The study confirms the high prevalence of cardiovascular manifestations in NS and highlights genotype-phenotype correlations. While cardiac abnormalities are common, their impact on psychomotor development and stature is less clear. Further research is needed to explore genetic interactions influencing these outcomes and refine clinical management strategies.