Clinical and Genetic Characterization of Noonan Syndrome in a Colombian Pediatric Cohort.
[OBJECTIVE] This study aimed to describe the clinical manifestations and genetic variants of Noonan syndrome in a Colombian pediatric population and to identify the genes most frequently associated wi
APA
Martínez Rueda SC, Del Pilar Montilla M, et al. (2026). Clinical and Genetic Characterization of Noonan Syndrome in a Colombian Pediatric Cohort.. Journal of clinical research in pediatric endocrinology. https://doi.org/10.4274/jcrpe.galenos.2026.2025-10-7
MLA
Martínez Rueda SC, et al.. "Clinical and Genetic Characterization of Noonan Syndrome in a Colombian Pediatric Cohort.." Journal of clinical research in pediatric endocrinology, 2026.
PMID
41988663
Abstract
[OBJECTIVE] This study aimed to describe the clinical manifestations and genetic variants of Noonan syndrome in a Colombian pediatric population and to identify the genes most frequently associated with specific phenotypic features.
[METHODS] A retrospective observational study was conducted on 45 patients under 18 years of age diagnosed with NS between 2013 and 2023. Clinical and molecular data were collected from medical records across several hospitals in Colombia. Molecular confirmation was achieved in all included patients through NGS-based clinical exome sequencing; however, parental samples were not available for segregation analysis in all cases. Descriptive statistical analyses were performed using R version 4.3.1 to evaluate demographic, clinical, and genetic variables.
[RESULTS] Among 45 patients (21 females, 24 males; the mean age at diagnosis was 7.5 ± 5.2 years), pathogenic variants were identified across 13 genes, with being the most frequent (26/45, 57.8%), followed by and several less frequent genes including and . The most common phenotypic features were congenital heart defects (80%, 36/45), predominantly pulmonary stenosis (31.1%, 14/45), short stature (66.7%, 30/45), and learning difficulties (51.1%, 23/45). Seven patients developed neoplasms. Juvenile myelomonocytic leukemia was the most frequent neoplasm and occurred mainly in patients with variants. Ten patients received growth hormone therapy.
[CONCLUSION] This study represents the first genetically characterized Colombian cohort for NS. was the predominant gene identified, particularly the p.(Asn308Asp) variant. These findings underscore the genetic heterogeneity of NS and emphasize the importance of early molecular diagnosis to guide clinical management. Multidisciplinary follow-up is essential due to the risks of growth failure, cardiac anomalies, and malignancies.
[METHODS] A retrospective observational study was conducted on 45 patients under 18 years of age diagnosed with NS between 2013 and 2023. Clinical and molecular data were collected from medical records across several hospitals in Colombia. Molecular confirmation was achieved in all included patients through NGS-based clinical exome sequencing; however, parental samples were not available for segregation analysis in all cases. Descriptive statistical analyses were performed using R version 4.3.1 to evaluate demographic, clinical, and genetic variables.
[RESULTS] Among 45 patients (21 females, 24 males; the mean age at diagnosis was 7.5 ± 5.2 years), pathogenic variants were identified across 13 genes, with being the most frequent (26/45, 57.8%), followed by and several less frequent genes including and . The most common phenotypic features were congenital heart defects (80%, 36/45), predominantly pulmonary stenosis (31.1%, 14/45), short stature (66.7%, 30/45), and learning difficulties (51.1%, 23/45). Seven patients developed neoplasms. Juvenile myelomonocytic leukemia was the most frequent neoplasm and occurred mainly in patients with variants. Ten patients received growth hormone therapy.
[CONCLUSION] This study represents the first genetically characterized Colombian cohort for NS. was the predominant gene identified, particularly the p.(Asn308Asp) variant. These findings underscore the genetic heterogeneity of NS and emphasize the importance of early molecular diagnosis to guide clinical management. Multidisciplinary follow-up is essential due to the risks of growth failure, cardiac anomalies, and malignancies.