Breast cancer (BC) remains one of the most prevalent malignancies worldwide, and genetic factors may influence its development. Approximately 10–15% of all BCs are hereditary and known as Hereditary Breast Cancer (HBC). A remarkable family history and young onset are the strongest risk factors of HBC. The rapid development of genetic testing techniques has increased the detection rate of pathogenic and likely pathogenic variants in several genes associated with high, moderate, or low risk of HBC. This allowed us to identify the whole family at risk of HBC. Among hereditary cases, pathogenic variants (PVs) in the BRCA1 and BRCA2 genes are particularly notable, especially in certain populations where founder mutations (specific genetic variants originating from a common ancestor) are more prevalent. In this article, an overview of the current state of knowledge on HBC is provided, focusing on the frequency of founder mutations in the BRCA1 and BRCA2 genes in HBC in Poland compared to other countries. We will also highlight the role of genetic counseling in the diagnosis and treatment of BC, emphasizing its crucial importance in identifying genetic predispositions, selecting appropriate therapeutic strategies, and supporting patients and their families in making informed medical decisions.

Background/Objectives: Overgrowth syndromes (OGSs) are a heterogeneous group of rare conditions marked by excessive growth and variable neurodevelopmental and systemic features. They are broadly classified into generalized overgrowth (GOG) and segmental overgrowth (SOG), which differ in clinical presentation and genetic mechanisms. However, many cases remain genetically unresolved, especially in underrepresented populations. Methods: We analyzed a binational cohort of patients from Poland and Lithuania with suspected OGSs, using detailed clinical evaluation and exome sequencing (ES) from blood-derived DNA. Variants were interpreted using current clinical guidelines, and phenotypes were compared between the GOG and SOG groups. Results: Patients with GOG more often showed developmental delay, intellectual disability, neurological issues, and joint laxity, while vascular malformations were more common in patients with SOG. Dysmorphic features appeared earlier in the SOG group, but became more pronounced over time in the GOG group. Genetic analysis led to the identification of definitive diagnoses in 25% of individuals. Pathogenic variants were identified in the genes involved in chromatin regulation and epigenetic control (DNMT3A, EED, KMT5B, CHD3, and NSD1), along with novel variants expanding the known spectrum. Conclusions: These findings provide valuable insights into the genetic architecture of OGSs in underrepresented Central and North-Eastern European populations, supporting the development of region-specific diagnostic and surveillance strategies.