Authors: Laura María Zabala Sepúlveda , Lina Johanna Moreno Giraldo

Abstract

Background: Noonan syndrome (NS) is an autosomal dominant condition characterized by facial dysmorphism, congenital heart disease, growth impairment, and ectodermal findings. Variants in SOS1 account for a large proportion of cases.

Case presentation: We report a male infant with nasal bone hypoplasia and shortening of long bones identified during the prenatal period. After birth, he presented with facial dysmorphism, pulmonary valve stenosis, axial hypotonia, and renal anomalies. The karyotype was normal. Whole-exome sequencing with CNV analysis focused on NS-related genes identified a heterozygous SOS1 variant, c.1656G>T (p.Arg552Ser), classified as pathogenic according to ACMG criteria and curated databases, supporting the diagnosis of SOS1-related Noonan syndrome type 4. The SOS1 p.Arg552Ser variant has been reported in individuals with typical NS features, supporting the genotype–phenotype correlation. In this patient, the combination of prenatal skeletal markers and postnatal renal involvement illustrates the wide phenotypic variability. Early molecular confirmation allowed multidisciplinary care and targeted surveillance (cardiac, endocrine, and oncologic), as well as genetic counseling.

Conclusion: This case highlights the diagnostic utility of early exome sequencing when NS is suspected, but
the phenotype is incomplete, and emphasizes the value of integrating prenatal markers with postnatal findings to enable timely management guided by precision medicine.

Keywords: Noonan syndrome, SOS1 gene, RAS/MAPK, RASopathies, phenotypic variability, precision diagnosis, personalized treatment.