The 15q11.2q13 chromosomal region is particularly susceptible to chromosomal rearrangements due to low-copy repeats (LCRs) located inside this area. Specific breakpoints (BP1-BP5) that lead to deletions and duplications of variable size have been identified. Additionally, this specific region contains several imprinted genes, giving rise to complex syndromes (Prader–Willi, Angelman and 15q11-q13 duplication syndromes). 15q11.2-q13 duplication syndrome has been associated with neurodevelopmental disorders (hypotonia, developmental delay, speech delay and seizures) and ASD but is characterized by variable expressivity and reduced penetrance, features that make genetic counseling a complex procedure especially in prenatal cases. In the present study, a total of 14 pre- and postnatal cases were diagnosed as 15q11.2q13 duplication carriers using Affymetrix CytoScan 750 K array-CGH, and our analysis combined these with 120 cases existing in the literature. The inheritance pattern of the cases of this study is unknown, but as a review of the literature revealed, 62.96% of the affected carriers inherited the duplicated area from their mother. The combined results of this analysis (the present study and the literature) show that in the majority of the cases, the phenotype is a compound phenotype, with clinical characteristics that include ASD, intellectual disability, developmental delay and an absence of speech. The aim of this paper is to deliver new possibilities to genetic counseling that can be provided in prenatal and postnatal cases as the phenotype of 15q11.2q13 microduplication carriers cannot be fully predicted; so, clinical diagnoses should be a combination of molecular findings and clinical manifestations that are present.

Small supernumerary marker chromosomes (sSMCs) are rare chromosomal abnormalities with diverse outcomes and variable effects that can be detected prenatally. The clinical significance of low-level mosaic sSMCs is often uncertain, and postnatal follow-up is essential to assess phenotypic outcomes. A fetus in whom a low-level mosaic sSMC (8%) was detected during prenatal testing is reported. The sSMC was found in 12 out of 150 metaphases examined by conventional karyotype, followed by molecular cytogenetic analyses (chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH)). Detailed ultrasound examination during the whole pregnancy revealed no structural abnormalities or other fetal complications and the child was born at term. Postnatal clinical investigation was conducted to evaluate the phenotypic impact of the sSMC and demonstrated normal early growth and neurodevelopment during the first nine months of life. Prenatal testing revealed a de novo sSMC in a low-level mosaic state. Evaluation of the sSMC revealed that the origin is in the pericentromeric region of chromosome 8, consisting predominantly of heterochromatic but also of euchromatic material. Integrating prenatal detection, molecular characterization, and postnatal clinical evaluation is crucial for managing cases with low-level prenatal mosaic sSMCs. Comprehensive follow-up is essential for better prognostic counseling and management in affected children.

17p13 is a chromosomal region characterized by genomic instability due to high gene density leading to multiple deletion and duplication events. 17p13.3 microduplication syndrome is a rare condition, reported only in 40 cases worldwide, which is found in the Miller–Dieker chromosomal region, presenting a wide range of phenotypic manifestations. Usually, the duplicated area is de novo and varies in size from 1.8 to 4.0 Mbp. Critical genes for this region are PAFAH1B1 (#601545), YWHAE (#605066), and CRK (#164762). 17p13.3 microduplication syndrome can be categorized into two classes (Class I and Class II) based on the genes that are present in the duplicated area, which lead to different phenotypes. In this report, we present a new case of Class I 17p13.3 microduplication syndrome that presents with unilateral sensorineural hearing loss. Oligonucleotide and SNP array comparative genomic hybridization (a-CGH) analysis revealed a duplication of approximately 121 Kbp on chromosome 17p13.3, which includes YWHAE and CRK genes. Whole-exome sequencing (WES) analysis confirmed the duplication. Our patient has common clinical symptoms of Class I 17p13.3 microduplication syndrome, and in addition, she has unilateral sensorineural hearing loss. Interestingly, WES analysis did not detect any mutations in genes that are associated with hearing loss. The above findings lead us to propose that hearing loss is a manifestation of 17p13.3 duplication syndrome.

Background/Objectives: 22q11.2 microduplication syndrome is a rare genetic disorder characterized by the presence of one or two additional copies of a segment within the 22q11.2 region of chromosome 22. While much of the literature has focused on the deletion variant leading to DiGeorge syndrome, the duplication counterpart has gained increasing attention due to its clinical variability and under-recognition. This review aims to deliver new possibilities to genetic counseling that can be provided in prenatal and postnatal cases as the phenotype of 22q11.2 microduplication carriers cannot be fully predicted. Methods: In the present study, a total of 12 (5 prenatal and 7 postnatal) cases were diagnosed through array-CGH and combined with 679 (95 prenatal and 584 postnatal) cases reported in the literature. This review summarizes the published evidence available up to April 2025. Data on clinical presentations, genetic findings, diagnostic methodologies, and outcomes were extracted and analyzed. Results: The combination of our cases and the reported cases with 22q11.2 microduplication syndrome revealed a broad phenotypic spectrum. Common clinical features include neurodevelopmental disorders, and cardiac anomalies. Importantly, the syndrome exhibits variable expressivity and reduced penetrance, with more than 70% of the findings to be inherited by one of the parents. Conclusions: 22q11.2 microduplication syndrome presents a heterogeneous clinical picture with variable expressivity and incomplete penetrance, posing challenges in diagnosis and genetic counseling, particularly when predicting prenatal outcomes. Awareness of its diverse manifestations is crucial for clinicians to consider this syndrome in the differential diagnosis and to provide informed counseling.