Objective: To present both our center's and previously reported experience of prenatal diagnosis of Coffin-Siris syndrome (CSS) with regard to the laboratory testing and fetal features of this syndrome.
Methods:This was a retrospective study of eight pregnancies with fetal CSS identified by prenatal or postnatal genetic testing. Clinical and laboratory data were collected and reviewed for these cases, including maternal demographics, prenatal sonographic findings, chromosomal microarray and exome sequencing (ES) results, and pregnancy outcomes.Results: A total of eight cases of fetal CSS based on molecular testing were detected. Two cases presented with an increased nuchal translucency (NT) in the first trimester. The remaining six were identified at the second trimester scan.Agenesis of the corpus callosum (ACC) was the most common sonographic finding, accounting for 5/7 (71.4%) cases in which a second trimester sonogram was performed: four had ACC as an isolated finding, and one had additional features of cerebellar hypoplasia and left congenital diaphragmatic hernia.
Conclusion:CSS should be included in the differential diagnosis when ACC is found by prenatal ultrasound. Both chromosomal microarray and ES should be options when counseling patients with a structurally anomalous fetus.
Key points
What is already known on this topic?� Coffin-Siris syndrome (CSS) is inherited in an autosomal dominant manner; most affected individuals have the disorder as the result of de novo CSS-causing variants of genes in the BAF complex.� In postnatal patients, the diagnosis is based on the presence of major and at least one minor clinical sign.
What this study adds?� CSS should be included in the differential diagnosis when a fetus presents with agenesis of the corpus callosum.� In addition to chromosomal microarray, exome sequencing should be an option when counseling patients with a structurally anomalous fetus.Qiu-Xia Yu and Xiang-Yi Jing contributed equally to this study.
Objective
To examine the diagnostic yield of exome sequencing (ES) in singleton pregnancies with isolated fetal clubfoot.
Methods
Clinical data from singleton pregnancies with a sonographic diagnosis of isolated clubfoot and ES results between 2018 and 2021 were retrospectively obtained from a single referral medical center. The recorded data include maternal age, gestational age at sonographic diagnosis, the indication for genetic testing, ES results, and pregnancy outcomes.
Results
During the study period, 38 fetuses were prenatally diagnosed with isolated clubfoot by ultrasound and underwent ES after the copy number variant analysis was non‐diagnostic. Through the trio‐ES analysis, pathogenic or likely pathogenic variants were detected in 4 of 38 (10.5%) with the following genes: BRPF1, ANKRD17, FLNA, and KIF1A. All are de novo with three of autosomal dominant inheritance and one of X‐linked recessive inheritance.
Conclusion
Sonographic diagnosis of clubfoot, even isolated, increases the risk for monogenic syndromes. Exome sequencing should be an option for genetic investigation for such pregnancies.
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