Prenatal Diagnosis of FLNA-related Cerebral Periventricular Nodular Heterotopia Presented with Enlarged Cisterna Magna Identified in the Second Trimester: Two Cases Report

Abstract Periventricular nodular heterotopia (PVNH) is a malformation of cortical development. In this study, we present two cases of PVNH that showed a nonspecific prenatal phenotype. In Case 1, routine anatomical scanning revealed fetal mega cisterna magna (MCM) with a normal vermis at 23 weeks’ gestation. Chromosomal microarray analysis detected a pathogenic deletion of 256 kb at Xq28 encompassing the haploinsufficient FLNA gene. Family studies confirmed the presence of this deletion in the mother, who exhibited cardiac defects and bilateral PVNH but demonstrated normal psychomotor and cognitive development. In Case 2, second-trimester ultrasound examination showed fetal MCM alongside a normal vermis at 22 weeks’ gestation. No additional anomalies were observed on follow-up ultrasounds until term was reached. At 4 months old, the child experienced seizures with PVNH. The genetic evaluation identified a de novo pathogenic splicing variant c.7757-2A>C in FLNA . Our study indicates that while MCM is considered nonspecific, it is crucial to recognize its potential coexistence with PVNH-an association that may manifest later during pregnancy or after birth.