Prenatal diagnosis of fetuses with Emanuel syndrome: Results of ultrasound examination and invasive genetic testing

Abstract

Objective To investigate prenatal manifestations of Emanuel syndrome (ES) by retrospectively analyzing the results of prenatal diagnosis. Methods Thirteen fetuses were collected from five hospitals, of which six were confirmed with 47,der(22)t(11;22; ES) by karyotype and chromosomal microarray analysis (CMA). Seven were diagnosed with 46,t(11;22) balanced translocations by karyotype, including one de novo mosaic 46,XX,t(11;22). In 3/7, CMA was performed but did not identify chromosomal imbalances. The results of prenatal diagnoses were reviewed, including ultrasound examinations and genetic testing. Results In ES fetuses, the derivative 22 was consistently inherited from the mother, while in the balanced translocation group, the t(11;22) chromosome was of paternal origin in 3/6 cases, All ES fetuses presented with multiple abnormalities by ultrasound examinations. Diaphragm hernia (3/6), Dandy‐Walker complex (3/6), and kidney aplasia (3/6), were the most common ultrasound findings. Sonographic soft markers such as increased nuchal translucency, increased nuchal fold thickness appeared in 3 cases and all of these were associated with other anomalies. However, none of the ultrasound findings differentiated ES from other genetic syndromes during fetal period. Conclusions In this series, in fetuses with a der(22), the derivative chromosome was consistently of maternal origin. In contrast, 46,t(11;22) balanced translocations were of maternal or paternal origin. The results contribute to the literature regarding the fetal phenotype of ES. Due to the absence of specific features distinguishing ES from other genetic syndromes, confirming the diagnosis through invasive genetic testing is necessary.

Prenatal cfDNA Screening for Emanuel Syndrome and Other Unbalanced Products of Conception in Carriers of the Recurrent Balanced Translocation t(11;22): One Laboratory’s Retrospective Experience

“…Consistent with the previous literature, cases affected with ES in this cohort were primarily inherited from maternal translocations [2,4,7,9]. There was one case with an abnormal cfDNA result suggesting an atypical segregation, likely adjacent-2 segregation with der (11), that was from a known paternal translocation, but did not have confirmatory diagnostic testing.…”

“…Genes 2023, 14,1924 2 of 17 comprised of a duplication of 22q that is approximately 3-4 Mb in size and a duplication of chromosome 11q that is approximately 18 Mb in size [8,9]. Usually, unbalanced products can be detected by routine G-banded karyotype or FISH.…”

“…As a relatively common translocation, families who carry t (11;22) are presenting for reproductive care. Limited data exist on prenatal screening and the diagnosis of ES; biochemical screening for ES is not well studied; but, in one study, it is evident that biochemical screening is unlikely to be a sensitive (or specific) screen for the condition, as only one of eight cases across two cohorts had an abnormal biochemical screen [9,11]. Another study noted that only 16% of cases in a series of patients with ES had anomalies detected prenatally on ultrasound [2].…”

“…To our knowledge, this cohort is the largest published group of cases with prenatal screening for carriers of t (11;22). Two publications note a small number cases of ES identified via prenatal cfDNA screening [8,12], while prenatal serum biochemical screening has only been mentioned in a handful of publications and does not appear to have meaningful utility in screening for this condition [9,11]. Ultrasound findings for ES are non-specific and overlap with a variety of other genetic syndromes and may not be present in all cases of ES [2,5,23]; therefore, the absence of ultrasound findings may not be reassuring.…”