Bardet–Biedl Syndrome is a rare non-motile primary ciliopathy with multisystem involvement and autosomal recessive inheritance. The clinical picture is extremely polymorphic. The main clinical features are retinal cone-rod dystrophy, central obesity, postaxial polydactyly, cognitive impairment, hypogonadism and genitourinary abnormalities, and kidney disease. It is caused by various types of mutations, mainly in genes encoding BBSome proteins, chaperonins, and IFT complex. Variable expressivity and pleiotropy are correlated with the existence of multiple genes and variants modifiers. This review is focused on the phenomena of heterogeneity (locus, allelic, mutational, and clinical) in Bardet–Biedl Syndrome, its mechanisms, and importance in early diagnosis and proper management.

Vascular anomalies (VAs) are morphogenesis defects of the vascular system (arteries, capillaries, veins, lymphatic vessels) singularly or in complex combinations, sometimes with a severe impact on the quality of life. The progress made in recent years with the identification of the key molecular pathways (PI3K/AKT/mTOR and RAS/BRAF/MAPK/ERK) and the gene mutations that lead to the appearance of VAs has allowed the deciphering of their complex genetic architecture. Understanding these mechanisms is critical both for the correct definition of the phenotype and classification of VAs, as well as for the initiation of an optimal therapy and the development of new targeted therapies. The purpose of this review is to present in synthesis the current data related to the genetic factors involved in the etiology of VAs, as well as the possible directions for future research. We analyzed the data from the literature related to VAs, using databases (Google Scholar, PubMed, MEDLINE, OMIM, MedGen, Orphanet) and ClinicalTrials.gov. The obtained results revealed that the phenotypic variability of VAs is correlated with genetic heterogeneity. The identification of new genetic factors and the molecular mechanisms in which they intervene, will allow the development of modern therapies that act targeted as a personalized therapy. We emphasize the importance of the geneticist in the diagnosis and treatment of VAs, as part of a multidisciplinary team involved in the management of VAs.

Background/Objectives: Ulcerative colitis is a chronic inflammatory bowel disease whose incidence is steadily growing worldwide. The interactions between host genetic susceptibility, gut microbiota and environmental factors determine the onset and relapsing evolution of ulcerative colitis, making it a multifactorial disorder. Methods: A narrative review was conducted to synthesize the available literature on the genes and mechanisms related to ulcerative colitis. Results: The most important independent risk factor is genetics and the candidate genes are associated with inflammation, immune regulation and epithelial permeability. Multiple GWAS have already identified candidate genes and their polymorphisms implicated in ulcerative colitis pathogenesis. Genetic susceptibility is conferred by predisposing variants influencing disease onset and progression, as well as by epigenetic modifications (DNA methylation, microRNAs). Conclusions: This review summarizes the interactions between the functional products encoded by genes linked to ulcerative colitis and immunological factors revealing their common mechanisms.

In the modern era, coronary artery disease (CAD) has become the most common form of heart disease and, due to the severity of its clinical manifestations and its acute complications, is a major cause of morbidity and mortality worldwide. The phenotypic variability of CAD is correlated with the complex etiology, multifactorial (caused by the interaction of genetic and environmental factors) but also monogenic. The purpose of this review is to present the genetic factors involved in the etiology of CAD and their relationship to the pathogenic mechanisms of the disease. Method: we analyzed data from the literature, starting with candidate gene-based association studies, then continuing with extensive association studies such as Genome-Wide Association Studies (GWAS) and Whole Exome Sequencing (WES). The results of these studies revealed that the number of genetic factors involved in CAD etiology is impressive. The identification of new genetic factors through GWASs offers new perspectives on understanding the complex pathophysiological mechanisms that determine CAD. In conclusion, deciphering the genetic architecture of CAD by extended genomic analysis (GWAS/WES) will establish new therapeutic targets and lead to the development of new treatments. The identification of individuals at high risk for CAD using polygenic risk scores (PRS) will allow early prophylactic measures and personalized therapy to improve their prognosis.

Lower extremity artery disease (LEAD), caused by atherosclerotic obstruction of the arteries of the lower limb extremities, has exhibited an increase in mortality and morbidity worldwide. The phenotypic variability of LEAD is correlated with its complex, multifactorial etiology. In addition to traditional risk factors, it has been shown that the interaction between genetic factors (epistasis) or between genes and the environment potentially have an independent role in the development and progression of LEAD. In recent years, progress has been made in identifying genetic variants associated with LEAD, by Genome-Wide Association Studies (GWAS), Whole Exome Sequencing (WES) studies, and epigenetic profiling. The aim of this review is to present the current knowledge about the genetic factors involved in the etiopathogenic mechanisms of LEAD, as well as possible directions for future research. We analyzed data from the literature, starting with candidate gene-based association studies, and then continuing with extensive association studies, such as GWAS and WES. The results of these studies showed that the genetic architecture of LEAD is extremely heterogeneous. In the future, the identification of new genetic factors will allow for the development of targeted molecular therapies, and the use of polygenic risk scores (PRS) to identify individuals at an increased risk of LEAD will allow for early prophylactic measures and personalized therapy to improve their prognosis.

Acromegaly is a rare chronic endocrine disorder characterized by delayed diagnosis, multisystem comorbidity, and heterogeneous therapeutic response. We aimed to describe the clinical characteristics, tumor profile, treatment patterns, biochemical control, pituitary insufficiencies, and comorbidity burden in an endocrinology tertiary center in northeastern Romania. This observational retrospective study included 87 adult patients admitted for general inpatient evaluation between December 2023 and November 2024, with retrospective data collected from diagnosis and follow-up assessed through the last available hospital visit at St. Spiridon Clinical Emergency Hospital. Clinical, hormonal, imaging, and therapeutic data were analyzed using descriptive statistics and inferential statistical tests. Most patients were diagnosed in middle adulthood, with a female predominance. Macroadenomas and extrasellar extension were common, consistent with advanced tumor stage at presentation. Treatment was predominantly multimodal, with surgery as the main therapeutic intervention and somatostatin receptor ligands as the main medical treatment backbone. Biochemical improvement was observed over time, although complete remission was achieved only in a subset of patients. These findings describe the clinical and therapeutic complexity of acromegaly in a single tertiary-center inpatient cohort and support the need for individualized long-term monitoring.