Congenital heart defects (CHDs) have had an increasing prevalence over the last decades, being one of the most common congenital defects. Their etiopathogenesis is multifactorial in origin. About 10–15% of all CHD can be attributed to copy number variations (CNVs), a type of submicroscopic structural genetic alterations. The aim of this study was to evaluate the involvement of CNVs in the development of congenital heart defects. We performed a cohort study investigating the presence of CNVs in the 22q11.2 region and GATA4, TBX5, NKX2-5, BMP4, and CRELD1 genes in patients with syndromic and isolated CHDs. A total of 56 patients were included in the study, half of them (28 subjects) being classified as syndromic. The most common heart defect in our study population was ventricular septal defect (VSD) at 39.28%. There were no statistically significant differences between the two groups in terms of CHD-type distribution, demographical, and clinical features, with the exceptions of birth length, weight, and length at the time of blood sampling, that were significantly lower in the syndromic group. Through multiplex ligation-dependent probe amplification (MLPA) analysis, we found two heterozygous deletions in the 22q11.2 region, both in patients from the syndromic group. No CNVs involving GATA4, NKX2-5, TBX5, BMP4, and CRELD1 genes were identified in our study. We conclude that the MLPA assay may be used as a first genetic test in patients with syndromic CHD and that the 22q11.2 region may be included in the panels used for screening these patients.

Background: Noonan syndrome (NS) is a genetically heterogeneous condition within the RASopathies spectrum, with distinctive craniofacial features, congenital heart defects, short stature, and variably present developmental delay. Most cases result from variants in genes regulating the RAS/MAPK pathway, with PTPN11 variants being the most frequent; the c.922A>G substitution being among the most commonly reported. Methods: This pilot study analyzed clinical and partial genetic features of NS in a cohort from Transylvania, evaluated in the Children’s Emergency Clinical Hospital in Cluj-Napoca. Thirty-one patients fulfilling the Van der Burgt diagnostic criteria (twenty-two males, nine females) were included. Clinical data were systematically reviewed, and targeted molecular testing for the PTPN11 c.922A>G variant was performed. Results: Congenital heart defects were highly prevalent, with pulmonary stenosis representing the most frequent anomaly (54.8%). Craniofacial dysmorphism was observed in 76.7% of cases, cryptorchidism in 50% of the males, and short stature below the third percentile was described in 77.4% of patients. Genetic screening identified the PTPN11 c.922A>G variant in two individuals (6.45%). Additional diagnoses included Williams–Beuren syndrome and a 17q11.2 deletion consistent with Neurofibromatosis–Noonan syndrome, underscoring the clinical and genetic heterogeneity of the cohort. Comparison with international reports highlighted variability in phenotype and variant frequency. Future research directions include Sanger sequencing of key PTPN11 exons and the application of next-generation sequencing targeting all RAS pathway genes. Conclusions: This is the first Romanian cohort study on patients with a clinical suspicion of NS, providing insight into their evaluation. The findings reinforce the need for comprehensive molecular approaches, facilitating diagnostic precision and counseling strategies.

Background/Objectives: Bicuspid aortic valve (BAV) is frequently associated with valvular dysfunction and aortic remodeling. This exploratory study examined cross-sectional associations between circulating extracellular matrix-related biomarkers and concurrent echocardiographic characteristics in children with BAV. Methods: We included 43 pediatric participants—26 with BAV and 17 with tricuspid aortic valves (TAV). All participants underwent clinical assessment, transthoracic echocardiography, and serum biomarker quantification at the same study visit. MMP-2, MMP-9, TIMP-1, and TGF-β1 were measured using ELISA. Biomarker levels were compared between the BAV and TAV groups and, within the BAV group, according to the presence of concurrent aortopathy, aortic stenosis, and aortic regurgitation. Results: MMP-9, TIMP-1, and the MMP-9/TIMP-1 ratio were higher in the BAV group than in the TAV comparison group. Within the BAV cohort, none of the investigated biomarkers differed significantly between participants with and without aortopathy. TGF-β1 was higher in BAV patients with aortic stenosis, whereas the MMP-9/TIMP-1 ratio showed a borderline difference according to aortic regurgitation status; these subgroup findings are exploratory and limited by small sample size and multiple comparisons. Conclusions: In this selected pediatric cohort, circulating MMP-9 and TIMP-1 levels differed between children with BAV and the TAV comparison group. However, none of the investigated biomarkers differed significantly between BAV patients with and without aortopathy. These cross-sectional findings describe exploratory associations with the BAV phenotype but do not establish diagnostic, predictive, or prognostic utility. Larger longitudinal studies including the broader clinical spectrum of BAV and independent validation cohorts are required.