The 2p duplication syndrome is a rare clinically heterogeneous disorder that arises from non-recurrent chromosomal rearrangements involving ~6 Mb up to ~90 Mb. The patients are characterized by a wide range of symptoms, including developmental delay, intellectual disability, distinctive facial features, congenital heart defects, and various ophthalmic manifestations. We report a male newborn with maternally inherited unbalanced translocations resulting in partial trisomy of chromosome 2p (33.9 Mb) - 46,XY,der(10)t(2;10)(p22.3;p1?5)dmat. Fluorescence in situ hybridization and chromosomal microarray analyses confirmed three copies of 2p25.3-p22.3 region, encompassing 51 known disease-causing genes. The patient presented with low birth weight, ventricular septal defect, camptodactyly of the 3rd digit of the left hand and mild early feeding problems. Ophthalmological assessment revealed macular and optic nerve hypoplasia. MRI demonstrated hypoplasia of the optic chiasm and optic nerves, and partial agenesis of falx cerebri. We describe macular and optic nerve hypoplasia in a patient with a novel chromosomal rearrangement resulting in 2p partial trisomy and provide an overview of 17 previously reported cases presenting ocular abnormalities. A broad variability of ophthalmological phenotypes has been observed, further expanded by the current report.

Trisomy 13 (T13) and trisomy 18 (T18) are chromosomal abnormalities with high mortality rates in the first year of life. Understanding differences in long-term survival between children with full vs mosaic or partial trisomy is crucial for prognosis and health care planning. To examine the differences in 10-year survival between children with full T13 and T18 vs those with mosaic or partial trisomy. This retrospective, population-based cohort study assessed liveborn infants with T13 and T18 in the Texas Birth Defects Registry (deliveries from January 1, 1999, to December 31, 2008). Follow-up was through December 31, 2018 (the last date available at the time of analyses) to allow for 10 years of follow-up for all infants. All analyses were conducted from January 1, 2022, to December 31, 2024. Cytogenetic status (full trisomy vs mosaic or partial trisomy). The primary outcome was survival to 10 years of age, assessed using Kaplan-Meier survival estimates. The association between cytogenetic status and mortality by 10 years of age was assessed using Cox proportional hazards regression to generate hazard ratios (HRs). Population attributable fraction was calculated to determine the percentage of survival attributable to mosaic or partial trisomy status. The study cohort included 798 infants (463 female infants [58.0%]; mean [SD] maternal age, 30.9 [8.0] years) with T13 (n = 295) or T18 (n = 503). Among all cases with T13, 25 infants (8.5%; 95% CI, 5.5%-12.3%) survived to 10 years of age. Similarly, among all infants with T18, 43 (8.6%; 95% CI, 6.3%-11.3%) survived to 10 years of age. Kaplan-Meier survival estimates to 10 years of age were statistically significantly higher among children with mosaic or partial trisomy (13 [25.0%] and 14 [43.8%], respectively) compared with full trisomy (12 [4.9%] and 29 [6.6%], respectively) (both P < .001). Infants with full trisomy had statistically significantly increased 10-year mortality hazards compared with those with mosaic or partial trisomy for both T13 (HR, 2.00; 95% CI, 1.42-2.82) and T18 (HR, 3.34; 95% CI, 2.08-5.38). The results of the calculated proportion of 10-year survival due to the presence of nonfull trisomy status (population attributable fraction) was 41.7% for children with T13 and 27.9% for children with T18. The findings of this cohort study of infants with T13 and T18 support differences in long-term survival based on cytogenetic status and emphasize the need to potentially reassess the context of these conditions generally being considered incompatible with life, particularly for those with mosaic trisomies. These findings offer context surrounding treatment decisions, such as withholding interventions, for affected infants in the future.

Identification of cytogenetic abnormalities is critical for the classification and risk stratification of myelodysplastic syndromes (MDS). Optical genome mapping (OGM) is an emerging cytogenomic platform that enables high-resolution genome-wide cytogenetic analysis. We analyzed bone marrow specimens of 236 MDS patients, 149 newly diagnosed and 87 with relapsed/refractory disease, using OGM, conventional karyotyping, and next-generation sequencing analysis. OGM and karyotyping showed concordant results in 68% of cases, including 34% with normal findings by both assays. OGM provided additional information in 27% of patients. Common abnormalities detected exclusively by OGM included chromoanagenesis (n = 33), KMT2A partial tandem duplication (n = 7), and MECOM rearrangement (n = 4). These OGM findings led to disease reclassification and/or changes in risk stratification in 14 patients (9.4%) with newly diagnosed MDS. In contrast, OGM failed to detect small clones or subclones in 5% of patients, resulting in risk group changes in 2% of newly diagnosed MDS patients. We conclude that OGM enhances the cytogenetic assessment of MDS in approximately 25% of patients and leads to a change in disease classification and/or risk stratification in approximately 10% of patients. However, low sensitivity for detecting small clones or subclones remains a limitation of OGM.

We present first-trimester application of expanded non-invasive prenatal testing (NIPT) in the genetic investigation of fetal 1p36 deletion syndrome associated with a familial unbalanced reciprocal translocation of 46,XX,der(1)t(1;2) (p36.2;q37.3)dmat. A 37-year-old, gravida 2, para 0, woman underwent expanded NIPT at 13 weeks of gestation because of advanced maternal age and the fear of complications of invasive procedures of prenatal diagnosis. She had experienced one spontaneous abortion. The pregnancy was conceived by in vitro fertilization and embryo transfer (IVF-ET) because of tubal occlusion. NIPT was positive for 1p36 deletion. At 17 weeks of gestation, she underwent amniocentesis but intrauterine fetal death occurred after amniocentesis and the pregnancy was terminated. Amniocentesis revealed a derivative chromosome 1 with an aberrant short arm terminal segment of chromosome 1. Subsequent cytogenetic analysis of parental bloods showed a karyotype of 46,XY in the father and a karyotype of 46,XX,t(1;2) (p36.2;q37.3) in the mother. The karyotype of amniocytes was 46,XX,der(1)t(1;2) (p36.2;q37.3)dmat, consistent with partial monosomy 1p (1p36.2→pter) and partial trisomy 2q (2q37.3→qter). Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed the result of arr 1p36.33p36.22 (852,863-11,303,452) × 1.0 and arr 2q37.3 (242,785,405-243,068,396) × 3.0 [GRCh 37] with a 10.451-Mb deletion of 1p36.33-p36.22 encompassing 116 OMIM genes including RERE and a 283-kb duplication of 2q37.3 encompassing one OMIM gene of PDCD1. Expanded NIPT has the advantage of early detection of familial unbalanced reciprocal translocation in the fetus.

We report data of non-invasive prenatal testing (NIPT) at Uppsala University Hospital between 2017-2022. Furthermore, we illustrate the potential capacity of massive parallel sequencing-based NIPT beyond identification of common trisomies. Maternal blood samples were analyzed using the Verifi NIPT or VeriSeq NIPT assays. Diagnostic testing, performed on amniotic fluid samples, included QF-PCR, microarray (SNP-array) and metaphase FISH. Among 4532 NIPT tests performed between 2017-2022, 125 samples (2.76%) showed increased risk for trisomies 13, 18, 21 and sex chromosome aneuploidy. For three patients with normal NIPT result further microarray indicated other types of chromosomal rearrangement which were not analyzed by NIPT. For another patient (case 1) the Verifi NIPT indicated trisomy 13. Fetal fraction (FF) was estimated to be 10%. Confirmatory microarray detected a segmental duplication on chromosome 13, as well as a terminal duplication and a terminal deletion on chromosome 10. A complex karyotype was observed in the fetus with metaphase FISH. In the second case the VeriSeq NIPT indicated trisomy 13. FF was estimated to be 11%. Confirmatory microarray detected a mosaicism of trisomy 13 in 30 % of cells. This study illustrates detection of peculiar abnormalities of chromosome 13 and supports potential to screen copy number variations with genome-wide NIPT.