Emanuel syndrome is a rare chromosomal disorder characterized by severe developmental disability and variable clinical manifestations. Although congenital anomalies are relatively common, there is no pathognomonic prenatal pattern. In some cases, structural defects are absent or not detectable prenatally, making the potential role of soft ultrasound markers particularly relevant. We report a case of Emanuel syndrome in which no structural malformations were identified prenatally. First-trimester ultrasound revealed an isolated increased nuchal translucency of 3.2 mm. Postnatally, the infant exhibited severe hypotonia, dysmorphic features, and profound developmental delay, but no gross structural defects were observed. Cytogenetic and FISH analyses confirmed an additional der(22)t(11; 22) chromosome inherited from the mother. A review of the limited literature on first-trimester findings suggests that increased nuchal translucency has been observed in several cases of Emanuel syndrome, although the available data remain insufficient to assess predictive value. Nevertheless, the recurrence of this observation across independent reports indicates that NT enlargement may warrant attention as a potential prenatal marker. While current evidence is insufficient to draw definitive conclusions, this case highlights that isolated NT thickening may represent the only prenatal sign of Emanuel syndrome. Evaluation in larger cohorts and future prospective studies will be essential to determine the sensitivity and specificity of this marker for early diagnosis of the syndrome and the timely identification of balanced translocation carriers.

Emanuel syndrome is a rare inherited chromosomal disorder characterized by the presence of a derivative chromosome 22 resulting from a translocation between chromosomes 11 and 22. Since the number of reported cases in Asian is still small, we mean to present 2 more cases diagnosed prenatally and review similar case reports to better understand the syndrome when abnormal findings were found prenatally. Two cases of Emanual syndrome were found where one draws attention due to abnormal serum marker and thickened nuchal translucency, and the other was found when prenatal ultrasonography detected multiple anomalies. Genetic amniocentesis revealed 47 chromosomes gaining an additional marker chromosome arising from malsegregation in a balanced translocation heterozygote with 46, XX, t(11;22) (q23.3;q11.2). While different anomalies were found, both of our cases along with others presented 3:1 segregation with tertiary trisomy resulting in Emanual syndrome. Chromosome of the quadrivalent is small in content ("lop-sided" quadrivalent) at meiosis I, which tends to separate in a 3:1 segregation fashion.

Emanuel syndrome is a rare autosomal disorder characterized by microcephaly, heart defects, cleft palate and developmental delay. However, there is a lack of specific prenatal screening for Emanuel syndrome. To screen for early diagnostic marker genes in fetuses with karyotype+der[22]t(11;22)(q23;q11) of Emanuel syndrome. Transcriptome sequencing and clinical trait data of t(11;22)(q23;q11) translocation samples were screened from the GEO database. The differentially expressed genes (DEGs) were screened by principal component analysis of gene expression by R package, and intersections were taken with balanced and unbalanced DEGs. Then, the correlation with clinical traits was determined by WGCNA analysis, GO and KEGG enrichment analysis, and then univariate Cox analysis and Lasso analysis were performed to obtain the key genes. The core regulatory genes were obtained after protein-protein interaction (PPI) network analysis. A total of 50 DEGs were obtained after differential analysis. WGCNA analysis showed that DEG was associated with the chromosomal imbalance and age module. GO and KEGG enrichment analyses showed candidate genes were associated with exocytic vesicle membrane, synaptic vesicle membranes, glycoprotein complex, dystrophin-associated glycoprotein complex and malaria. COX and Lasso analyses yielded 5 hub genes, including ZBED9, RGS20, SGCB, ETV5, and ZAP70. The results of PPI identified the key regulatory gene associated with chromosomal imbalance as the ZAP70 gene. ZAP70 may be a key gene for early diagnosis of Emanuel syndrome in fetuses with+der[22]t(11;22)(q23;q11) karyotype.

The 22q11.2 region is highly susceptible to genomic rearrangements leading to multiple genomic disorders, including 22q11.2 microdeletion syndrome (22q11.2 DS) (MIM# 188400), 22q11.2 microduplication syndrome (MIM# 608363), supernumerary der(22)t(11;22) syndrome (also known as Emanuel Syndrome; MIM# 609029), and Cat Eye Syndrome (MIM# 115470). In this study, we present data on causes of mortality, average age of death, and the existing associated risk factors in patients with 22q11.2 rearrangements. Our cohort included 223 patients (120 males and 103 females) with confirmed diagnoses of 22q11.2 rearrangements diagnosed through molecular techniques (FISH, MLPA, and CMA). Relatives from patients who have been molecularly confirmed with 22q11.2 rearrangements have also been added to the study, regardless of the presence or absence of symptoms. Of these 223 individuals, 21 (9.4%) died. Deceased patients' rearrangements include 19 microdeletions, 1 microduplication, and 1 patient with a marker chromosome. The median age of death was 3 months and 18 days (ranging from 3 days to 34 years). There were 17 patients who died at pediatric age (80.95%), 3 died at adult age (14.28%), and for 1 of whom, the age of death is unknown (4.76%). Eighteen patients were White Mediterranean (European non-Finnish) (85.71%) whereas three were Amerindian (South American) (14.28%). Mortality from cardiac causes accounted for 71.42%. The second most frequent cause of death was sepsis in two patients (9.52%). One patient died from respiratory failure (4.76%) and one from renal failure (4.76%). Information regarding the cause of death was not available in two patients (9.52%). Most patients who died were diagnosed within the first week of life, the majority on the first day. This study adds additional information on mortality in one of the largest cohorts of patients with 22q11.2 rearrangements in more than 30 years of follow-up.

Small supernumerary marker chromosomes (sSMCs) are additional chromosomes with unclear structures and origins, and their correlations with clinical fetal phenotypes remain incompletely understood, which reduces the accuracy of genetic counseling. We conducted a retrospective analysis of a cohort of 36 cases of sSMCs diagnosed in our center. We performed G-banding and chromosomal microarray analysis (CMA). The resulting karyotypes were compared with case reports in the literature and various databases including OMIM, DECIPHER, ClinVar, ClinGen, ISCA, DGV, and PubMed. Karyotype analysis data revealed that 19 out of 36 fetuses were mosaic. Copy number variants (CNVs) analysis results showed that 27 out of 36 fetuses harbored pathogenic/likely pathogenic variants. Among these 27 cases, 11 fetuses carried sex chromosome-related CNVs, including 4 female cases exhibiting Turner syndrome phenotypes and 7 cases showing Y chromosome deletions. In the remaining 16 fetuses with autosomal CNVs, 9 fetuses carried variants associated with Cat eye syndrome, Emanuel syndrome, Tetrasomy 18p, and 15q11-q13 duplication syndrome. Among these, 22 fetuses were terminated, and the remaining 5 fetuses were delivered and developed normally. Additionally, we identified a few variants with unclear pathogenicity. Cytogenetic analysis is essential for identifying the pathogenicity of sSMCs and increasing the accuracy of genetic counseling.