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

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.

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).

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.

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.