Globally, chronic kidney disease (CKD) affects over 800 million individuals and is characterized by significant genetic complexity. More than 600 genes are associated with hereditary kidney disease, which may manifest as isolated kidney issues or as part of a syndrome that also includes extrarenal manifestations. The aim of this study was to identify genetic variants in a group of ten patients who presented with clinical signs suggestive of genetic syndromes associated with CKD, or who were asymptomatic but had a positive family history of CKD. Extensive genetic testing (targeted gene panels and whole-exome sequencing—WES) identified a mutation in the PKD1 gene in 3 out of 10 cases. In one patient, a known mutation in the PKD2 gene was identified. Another four patients were diagnosed with Alport syndrome: three of these presented with de novo missense mutations in the COL4A5 gene, and one patient had a mutation in the COL4A3 gene. One patient was diagnosed with MODY5, caused by a known mutation in the HNF1B gene, and one patient was diagnosed with Bartter syndrome type 1, resulting from a known mutation in the SLC12A1 gene. We present genotype–phenotype correlations, highlighting the particularities of each patient within their family context. Our findings emphasize the importance of genotype–phenotype correlations in refining diagnosis, personalizing therapeutic management, and providing essential genetic counseling for at-risk relatives.

Epilepsy ranks among the most prevalent neurological disorders globally, with a substantial proportion of cases, particularly in pediatric populations, attributed to genetic etiologies. This study provides the first molecular characterization of suspected genetic epilepsy in a pediatric cohort from the Moldova region of Romania. Following the exclusion of 124 patients with secondary acquired or structural causes from an initial cohort of 159, we enrolled 35 individuals with a high suspicion of primary genetic epilepsy, who underwent targeted gene panel testing or whole-exome sequencing (WES). Pathogenic (P) or likely pathogenic (LP) variants were identified in 13 patients (37.1%); variants of uncertain significance (VUSs) were identified in another 13 patients (37.1%), comprising 15 distinct VUSs; and negative results were observed in the remaining 9 patients (25.7%). Genes regulating ion channels and synaptic signaling, notably SCN1A, KCNB1, and GNAO1, were predominantly implicated in early-onset, drug-resistant epileptic encephalopathies, whereas structural copy number variations (CNVs) underpinned syndromic phenotypes. We identified one novel pathogenic variant in SCN1A, thereby expanding the known mutational spectrum. Furthermore, in silico predictions and de novo occurrence patterns supported the pathogenicity of several VUSs, underscoring the critical value of familial segregation analyses. Despite the notable diagnostic yield, the high VUS rate underscores the ongoing need for refined variant interpretation criteria and the integration of functional validation data to improve classification accuracy. Collectively, our findings support the clinical utility of next-generation sequencing (NGS) in informing therapeutic decisions, enabling genetic counseling, and improving prognostic accuracy. These results suggest that NGS should be considered early in the diagnostic workup of unexplained or drug-resistant epilepsy, particularly in patients with clinical features suggestive of a genetic etiology.