What question did this study set out to answer?

This case aims to expand understanding of Noonan syndrome manifestations linked to a pathogenic SOS1 variant.

February 6, 2026Journal of Biochemical and Clinical Genetics0 citationsOpen Access

Noonan syndrome caused by a pathogenic SOS1 variant: expanding the phenotypic spectrum and molecular correlations

LSLaura María Zabala Sepúlveda LGLina Johanna Moreno Giraldo

Key Points

This case aims to expand understanding of Noonan syndrome manifestations linked to a pathogenic SOS1 variant.
Reported a male infant with prenatal and postnatal features suggestive of Noonan syndrome.
Performed whole-exome sequencing with copy number variation analysis focusing on NS-related genes.
Identified a heterozygous pathogenic SOS1 variant, c.1656G>T (p.Arg552Ser).
Integrated prenatal skeletal markers and postnatal findings for diagnosis.
The identified SOS1 variant is associated with typical Noonan syndrome features.
Illustrated phenotypic variability, with significant skeletal and renal manifestations.
Facilitated multidisciplinary care and proactive surveillance in affected individuals.

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.1656GT (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 genotypephenotype 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, butthe phenotype is incomplete, and emphasizes the value of integrating prenatal markers with postnatal findings to enable timely management guided by precision medicine.

Demander à l'IA

Bookmark

View Full Paper