Clinical and molecular analysis of 26 individuals with Noonan syndrome in a reference institution in Colombia

Abstract

Our aim was to characterize the phenotype and genotype of individuals with Noonan syndrome in Colombia. There are published cohorts of Noonan individuals from several countries in Latin America including Brazil, Chile, and Argentina, but none from Colombia. We described 26 individuals with NS from a single large referral center in the South West of Colombia using an established database in the genetics department and hospital records search using ICD‐10 codes. All patients included in this study were evaluated by a medical geneticist and have molecular confirmation of NS diagnosis. The median age at referral was 3.5 years (range, 0–39), and at molecular diagnosis was 5 years (range, 0–40). Patients mostly originated from the southwest region of Colombia (19/26, 73%). Pathogenic variants in PTPN11 are the most common cause of NS in Colombian individuals followed by SHOC2 and SOS1 variants. The prevalence of cardiomyopathy was low in this population compared to other populations. Further research is needed with a larger sample size and including different regions of Colombia to correlate our findings. This study provides new information about time to diagnosis of NS in Colombia, genotypes, and provides important information to help develop guidelines for diagnosis and management of this disease in the region.

Population-specific facial traits and diagnosis accuracy of genetic and rare diseases in an admixed Colombian population

“…In Noonan syndrome, we detected hypertelorism, downward slanting palpebral ssures, and midfacial hypoplasia in the Colombian population, as reported in populations of European descent [63] . In addition, our results quanti ed relative changes in the position of the mouth in Colombian individuals diagnosed with NS not reported before [73] .…”

Population-specific facial traits and diagnosis accuracy of genetic and rare diseases in an admixed Colombian population

“…In Noonan syndrome, we detected hypertelorism, downward slanting palpebral fissures, and midfacial hypoplasia in the Colombian population, as reported in populations of European descent (Athota et al, 2020). Moreover, our results quantified changes in the position of the mouth in Colombian individuals diagnosed with NS not reported before (Lores et al, 2020).…”

Mowat-Wilson Syndrome as a Differential Diagnosis in Patients with Congenital Heart Defects and Dysmorphic Facies

“…In the diagnostic work-up for this case, a RASopathy panel was performed due to the combination of features resembling Noonan syndrome (NS) such as short stature, intellectual disability, pulmonary valve stenosis, high forehead, and low-set ears. 16 This highlights the utility of a wide-scope diagnostic test such as clinical exome in the setting of patients with developmental delay/intellectual disability and multiple congenital malformations, and adds MWS to the long list of potential differential diagnoses of NS and related RASopathies. 17 In Colombia, as far as we know, only four cases of MWS have been published, [18][19][20][21] from which, only one reported the genetic variant and it was a 2q22.32-q22.3 deletion, 19 including the KYNU, ARHGAP15, GTDC1 and ZEB2 genes.…”