Although extensively investigated, the genetic etiology of fetal growth restriction (FGR) has not been fully understood. Previous studies have shown the potential of karyotyping, chromosomal microarray analysis (CMA) and trio-based WES (trio-WES) in prenatal diagnosis, however, there is little knowledge on the comparative effectiveness of these three prenatal genetic tools. The present study aimed to evaluate and compare the effectiveness of karyotyping, CMA and trio-WES for prenatal diagnosis and prognostic evaluation of FGR, in order to identify the optimal genetic diagnostic testing of FGR. All clinical data were retrospectively collected from 388 pregnant women that received invasive prenatal diagnosis due to FGR in Wenzhou Central Hospital and Fujian Maternity and Child Health Hospital during the period from April 2015 to August 2024. All fetuses received karyotyping and CMA, and additional trio-WES was performed among 26 pregnancies negative for karyotyping and CMA. The effectiveness of karyotyping, CMA, and trio-WES alone and in combinations was evaluated for diagnosis of chromosomal abnormality in pregnancies with FGR, and the pregnancy outcomes were followed up. Karyotyping detected a 4.38% (17/388) chromosomal abnormality rate and CMA detected a 13.4% (52/388) chromosomal abnormality rate, which resulted in a 9.28% (36/388)incremental yield above karyotyping. The diagnostic yield of Karyotyping combined with CMA was 13.66% (53/388). The common microdeletion and microduplication syndromes included 4p16.3.3 microdeletion syndrome, 1q21.2 microduplication syndrome, 16p13.3 microdeletion syndrome and 22q11.21 microduplication syndrome. Trio-WES revealed a high detection rate (30.77%,8/26) for diagnosis of P/LP variants, and the growth- and development-related genes included IGF1R, GNAS, COL9A3, FGD1, FLNB, PORCN, EVC, OTX2 and GH1. Of all pregnancies with FGR, the proportions of live births, induced labors, natural abortion, perinatal mortality, and percentage of loss to follow-up were 70.62% (274/388), 19.84% (77/388), 0.52% (2/388), 1.80% (7/388) and 7.22% (28/388), respectively. Karyotyping combined with CMA remains the first-tier tool for prenatal genetic diagnosis of pregnancies with FGR, and additional trio-WES may increase the detection of chromosomal abnormality. IGF1R, GNAS, COL9A3 and FGD1 may be candidate genes causing FGR.

This case report outlines the management of a 16-month-old girl with chromosome 16p13.3 microduplication syndrome who presented with an acute respiratory illness. For signs and symptoms of croup, pneumonia, and otitis media, this patient required multiple administrations of racemic epinephrine, steroids, and albuterol to reduce inflammation and alleviate respiratory distress. Children with underlying medical conditions and genetic syndromes are likely to have a more complicated clinical course in the setting of acute illnesses. Thus, these patients require more intensive interventions and prolonged monitoring than the standard protocols. In this case, the treatment regimen was carefully tailored, with special attention to minimizing the risk of seizure activity. Furthermore, this case highlights the need for further exploration of the interaction between respiratory illnesses and underlying seizure disorders. The patient's presentation underscores the importance of neurological observation and a multidisciplinary approach to ensure the best possible outcome.

Partial 16p trisomy syndrome is a rare disorder typically characterized by psychomotor retardation, prenatal and postnatal growth deficiency, cleft palate, and facial dysmorphism, with some patients also presenting with heart defects and urogenital anomalies. Pure 16p13.3 duplications usually occur de novo, while those duplications that associate with partial monosomy result rather from parental chromosomal translocations. Due to the large size of the aberrations, the majority of patients are identified by standard chromosome analysis. In all published cases, the minimal-causative duplicated region encompasses the CREBBP gene. Here, we report on the patient presenting with psychomotor retardation, femoral hypoplasia, and some features of the partial 16p trisomy syndrome, who carries a complex de novo terminal 16p13.3 microduplication with an overlapping region of amplification without translocation or associated monosomy. In contrast to the previously reported cases, the duplicated region of the patient does not involve CREBBP and other neighboring genes; still, the observed pattern of dysmorphic features of the index is characteristic of the described syndrome. Based on the animal studies and other published cases, we discuss the possible role of the PDK1 and IGFALS genes in the development of limb anomalies, while IFT140 could contribute both to the observed femoral phenotype and heart abnormalities in the patient. To the best of our knowledge, we present a proband harboring the smallest terminal 16p13.3 duplication of the size below 3 Mb. Therefore, our proband with her detailed phenotypic description may be helpful for clinicians who consult patients with this syndrome.

Characteristic phenotypic features of 16p13.3 microduplication include impaired mental development, arthrogryposis-like musculoskeletal anomalies (club-feet, congenital hip dislocation, and camptodactyly of fingers and toes), facial dysmorphology, and at times congenital cardiac disease. Most of the described affected individuals have microduplications involving the CREBBP gene. Findings indicate this gene to be dosage-sensitive and likely involved in the phenotypes of 16p13.3 microduplication syndrome. We describe the incidental finding of 16p13.3 microduplication in a fetus with mid-trimester sonographic examination showing absent nasal bone and transient unilateral hydronephrosis.

Major birth defects are inborn structural or functional anomalies with long-term disability and adverse impacts on individuals, families, health-care systems, and societies. Approximately 20% of birth defects are due to chromosomal and genetic conditions. Inspired by the fact that neonatal deaths are caused by birth defects in about 20 and 10% of cases in Iran and worldwide respectively, we conducted the present study to unravel the role of chromosome abnormalities, including microdeletion/microduplication(s), in multiple congenital abnormalities in a number of Iranian patients. In this descriptive cross-sectional study, 50 sporadic patients with Multiple Congenital Anomalies (MCA) were selected. The techniques employed included conventional karyotyping, fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), and array comparative genomic hybridisation (array-CGH), according to the clinical diagnosis for each patient. Chromosomal abnormalities and microdeletion/microduplication(s) were observed in eight out of fifty patients (16%). The abnormalities proved to result from the imbalances in chromosomes 1, 3, 12, and 18 in four of the patients. However, the other four patients were diagnosed to suffer from the known microdeletions of 22q11.21, 16p13.3, 5q35.3, and 7q11.23. In the present study, we report a patient with 46,XY, der(18)[12]/46,XY, der(18), +mar[8] dn presented with MCA associated with hypogammaglobulinemia. Given the patient's seemingly rare and highly complex chromosomal abnormality and the lack of any concise mechanism presented in the literature to justify the case, we hereby propose a novel mechanism for the formation of both derivative and ring chromosome 18. In addition, we introduce a new 12q abnormality and a novel association of an Xp22.33 duplication with 1q43q44 deletion syndrome. The phenotype analysis of the patients with chromosome abnormality would be beneficial for further phenotype-genotype correlation studies.