Background/Objectives: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an established therapy for a range of hereditary disorders, including hemoglobinopathies, primary immunodeficiencies, and lysosomal storage diseases. Despite its long-standing use, rapid developments in donor availability, conditioning strategies, and supportive care have significantly broadened and refined its clinical application. This review combines recent evidence to clarify how these advances redefine current indications and therapeutic expectations. Methods: We critically analyze contemporary clinical data with a focus on elements that have undergone meaningful evolution—donor selection algorithms, conditioning intensity, graft manipulation, and post-transplant management. Comparative outcomes across major hereditary disease groups were examined to identify emerging trends in efficacy and safety. Results: The analysis highlights several novel shifts: expanding eligibility due to improved donor options, increasing reliance on reduced-toxicity regimens, and enhanced understanding of the mechanistic basis for hematologic, immunologic, and metabolic correction. These developments collectively improve survival and functional outcomes across diverse hereditary disorders. Conclusions: allo-HSCT remains a key therapeutic strategy for selected hereditary diseases, offering durable hematologic and metabolic correction. The prospective development of gene-addition and genome-editing therapies creates opportunities to complement—or in some cases replace—allo-HSCT, supporting the emergence of more personalized treatment approaches.

Intellectual disability is a widespread group of diseases with population frequency 1–3%. More than half of intellectual disability cases are due to various genetic causes, including monogenic ones. The paper describes three clinical cases of MED13L-associated intellectual disability with an autosomal dominant inheritance. Novel probably pathogenic variants p.Cys118delinsTrpSer and p.Gln2111fs, as well as the previously described p.Pro866Leu mutation in the MED13L gene (NM_015335), were detected in patients by massive parallel sequencing. А rare familial case with two affected maternal half-siblings was of particular interest since the mutation detected in both children was not found in the mother (blood cells and buccal epithelium were investigated). We assume the presence of gonadal mosaicism in the mother, which allows to recommend families with confirmed cases of MED13L-associated intellectual disability to plan pregnancies with prenatal or preimplantational diagnostics. The disease has been shown to have a wide clinical variability, even intrafamilial.

Marfan syndrome (OMIM #154700) is an autosomal dominantly inherited connective tissue disorder caused by mutations in the FBN1 gene and is marked by significant clinical variability, including cardiovascular manifestations. The causes of this variability remain inadequately studied, and relatively few genotype-phenotype correlations have been identified to date. In this study, we examined 66 children with Marfan syndrome to identify genotype-phenotype correlations. Biochemical, functional, and genetic research methods were employed, confirming a positive correlation between ectopia lentis and missense variants in the FBN1 gene. Additionally, in our cohort, patients with loss-of-function (LoF) mutations, compared to those with missense mutations, statistically showed larger aortic dimensions, earlier onset of foot deformities, marked dolichostenomelia, a higher frequency of elbow contractures, chest deformities, and aortic dilation. Patients with missense variants involving cysteine loss, as opposed to those without cysteine involvement, demonstrated an earlier onset of spinal deformity, higher natriuretic peptide (NT-proBNP) levels, larger aortic sizes, increased prevalence of chest deformities, particularly carinatum, ectopia lentis, and a greater propensity for osteoporosis. Patients with mutations in exons 11 to 20, compared to those with mutations in other exons, were less likely to exhibit pectus carinatum and aortic dilation and had less pronounced dolichostenomelia. Patients with mutations in exons 51 to 66, regardless of mutation type, were less likely to present with ectopia lentis. Thus, based on an analysis of genotype-phenotype correlations in a cohort of 66 children with Marfan syndrome, we identified several statistically significant correlations between phenotypic features of Marfan syndrome and mutation type and location within the FBN1 gene. This study confirmed that stable genotype-phenotype correlations are increasingly important for understanding clinical variability and for predicting disease severity.

DMD is a gene located on X chromosome that is responsible for the formation of the dystrophin protein. Pathogenic variants in the DMD gene cause diseases such as Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). DMD is characterized by progressive muscle weakness, leading to loss of motor and respiratory functions, as well as cardiomyopathy and progressive heart failure due to the complete absence of dystrophin in the body. Patients with BMD synthesize a reduced amount of dystrophin, which distinguishes it from DMD by a milder clinical picture and an older age of onset. Cardiomyopathies are a common and, in some cases, the main manifestation of these pathologies. This review focuses on studies of diseases associated with dystrophinopathies, in which the main symptom is heart injury, cardiomyopathy, and also provides information about modern approaches to gene and targeted therapy for these diseases.

Biallelic pathogenic variants of the AIRE gene lead to the development of autoimmune polyglandular syndrome type 1 (APS1; OMIM: 240300). The syndrome most often manifests with chronic candidiasis of the skin and mucous membranes in early childhood. As the disease progresses, hypoparathyroidism and Addison’s disease may be observed in the clinical picture. However, the symptoms of the disease are diverse and vary widely even among members of the same family. This article describes a patient - a three-year-old boy with signs of severe diarrhea and symptoms of hepatobiliary tract involvement. Skin and endocrine manifestations were absent at disease onset. Whole exome sequencing (WES) identified two previously described pathogenic variants in the AIRE gene: NM_000383.4: c.769C>T p.(Arg257Ter) and NM_000383.4: c.1302C>A p.(Cys434Ter). Sanger sequencing and family testing confirmed the compound heterozygous position of these variants. This case demonstrates an atypical manifestation of APS1: diarrhea with malabsorption syndrome and cholestatic liver disease.

Background/Objectives: TCIRG1-associated infantile osteopetrosis is a severe hereditary disorder caused by impaired osteoclast function, leading to osteosclerosis, hematological abnormalities, neurological complications, and early mortality. Early diagnosis and intervention are critical. Methods: A literature-based analysis was performed on clinical manifestations, outcomes of allogeneic hematopoietic stem cell transplantation (HSCT), immunomodulatory therapy, and experimental gene therapy and cell-based approaches, including lentiviral vectors and patient-derived induced pluripotent stem cells (iPSCs). Results: Allogeneic HSCT is the only established curative therapy, restoring osteoclast function and preventing severe complications. Early transplantation with HLA-matched donors and myeloablative conditioning provides optimal outcomes. Interferon γ1b can transiently enhance osteoclast activity but is not curative and shows variable efficacy. Preclinical studies demonstrate that lentiviral TCIRG1 delivery and transgenic correction in patient-derived iPSCs restore osteoclast function and bone resorption, with stable gene expression and minimal toxicity. Base and prime editing approaches offer potential for precise correction of single-nucleotide TCIRG1 variants, minimizing risks associated with double-strand DNA breaks. Conclusions: Allogeneic HSCT remains the standard therapy for TCIRG1-associated infantile osteopetrosis. Gene therapy and cell-based strategies represent promising adjuncts or alternatives, potentially avoiding immune-related complications and expanding therapeutic options. Further studies are needed to ensure safety, stable engraftment, and long-term efficacy, supporting translation of gene therapy into clinical practice.