Targeted Clinical Analysis of PTPN11, SOS1, and NRAS Mutations and Associated Cardiac, Auditory, and Ophthalmologic Findings in Noonan Syndrome Patients.

BACKGROUND

Noonan syndrome (NS) is a genetic disorder inherited as an autosomal dominant or sporadic trait, characterized by distinctive facial features, congenital heart defects, short stature, mental retardation, and sensory impairments. The aim was to investigate the clinical correlations of selected variants in the PTPN11, SOS1, and NRAS genes with ophthalmologic, audiologic, and psychometric findings in patients clinically diagnosed with NS.

METHODS

Thirty-two patients (8 females and 24 males) clinically diagnosed with NS and aged between 6 months and 18 years were included. Genetic testing was performed for PTPN11, SOS1, and NRAS genes. Patients underwent standardized examinations by the same ophthalmologist, audiologist, and psychologist. A comprehensive database of findings was created, and statistical analyses were performed using SPSS 17.

RESULTS

Molecular analysis revealed variants in PTPN11 gene in 37.5% (12/32), SOS1 related variants in 9.4% (3/32), and NRAS-related variant in 3.1% (1/32). Ophthalmologic assessments indicated astigmatism in 8 patients and myopia in 5. Hearing loss was identified in 21.9% (7/32) of the cohort, with two PTPN11 and one NRAS mutation-positive patients affected. Psychometric evaluations showed mental retardation in 40.6% (13/32), with a significant proportion of PTPN11 mutation-positive patients affected.

CONCLUSION

The study found no significant relationships between genetic mutations and ophthalmologic, audiologic, or psychometric outcomes. Further investigations with larger sample sizes are necessary to elucidate the genotype-phenotype correlations in NS.