Role of copy number variation analysis in prenatally diagnosed Blake's pouch cyst

Background: Blake's pouch cyst (BPC) is a midline cystic anomaly of the posterior fossa. BPC has been shown to have a risk of aneuploidy prenatally. Copy number variation (CNV) and/or genetic syndromes have been reported in a few prenatal/postnatal cases with BPC. The purpose of this study is to determine the additional value of CNV analysis for prenatal diagnosis and prognosis evaluation of BPC.

Methods: We reviewed the sonographic findings and genetic results of BPC diagnosed within 6 years at our center. Patients were classified into the isolated and non-isolated groups based on the prenatal and postnatal imaging. We analyzed the chromosomal abnormalities by conventional karyotype analysis combined with chromosomal microarray analysis (CMA) or CNV sequencing (CNV-seq).

Results: We recruited 467 low-risk fetuses as the control group to establish normal references of vermian area and brainstem-vermis (BV) angle. Prenatal/postnatal MRI or neonatal neurosonography was used as diagnostic criteria. 34 patients were diagnosed as BPC, including 21 (61.8%) patients with non-isolated and 13 (38.2%) with isolated. Twenty-two patients underwent CMA/CNV-seq, among them 14 patients were performed both CMA/CNV-seq and karyotype analysis. Seven (7/22, 31.8%) patients with BPC had chromosomal abnormalities, including 3 (3/22, 13.6%) patients with chromosomal aneuploidy - trisomy 21, 18 and 13, and 4 (4/22, 18.2%) patients had pathogenic CNVs located at 3p, 9p, Xp/Xq and 7p. Anomalies in fetal heart (35.3%), central nervous system (CNS) (26.5%) and limb (14.7%) were the three top anomalies accompanying BPC.

Conclusions: CNV analysis could provide some additional information for prenatal diagnosis and prognosis counseling for patients with non-isolated BPC. And, it adds less value for patients with isolated BPC, however, isolated BPC can be a soft marker for aneuploidy.