Prenatal Ultrasound and Genetic Analysis of PIK3CA-Related Fetal Overgrowth: A Case Report

Objective To analyze the ultrasonographic features and genetic etiology of fetal overgrowth caused by PIK3CA variant, and to provide references for prenatal diagnosis and genetic counseling. Method Whole exome sequencing was performed on the fetus and her parents. Sanger sequencing was used to verify the candidate pathogenic genes. Result At 27 ⁺⁶ weeks of gestation, the fetus showed an enlarged biparietal diameter (85.8mm) and head circumference (313.4mm), along with other abnormalities such as a widened Wechsler's lumen, a thinner corpus callosum, a widened third ventricle, a right choroid plexus cyst, and a single umbilical artery. MRI revealed an enlarged right lateral ventricle and bilateral subependymal cysts. By 30 ⁺⁰ weeks, these measurements continued to increase, and the forehead and hindbrain were notably prominent. Invasive prenatal diagnosis, including routine karyotype analysis and whole exome sequencing (WES), identified a de novel PIK3CA variant, c.1133G>A(p.Cys378Tyr), according to the ACMG guidelines, this variant was classified as likely pathogenic(PS2+PP2+PM2_Supportong+PP3). The condition was diagnosed as PIK3CA -related overgrowth spectrum, leading the family to terminate the pregnancy after ethical consultation. Conclusions Fetal overgrowth with macroencephaly is caused by a missense variant in PIK3CA . The discovery of this variant expands the phenotypic spectrum of PIK3CA and provides a new direction and basis for genetic counseling and prenatal diagnosis of fetal overgrowth.