Early diagnosis of fetal ganglionic eminence cysts: imaging, outcome and genetic associations, revealing role of mitochondrial dysfunction
Ultrasound Obstet Gynecol. 2026 Feb 12. doi: 10.1002/uog.70180. Online ahead of print.
ABSTRACT
OBJECTIVES: To characterize the sonographic features of fetal ganglionic eminence (GE) cysts diagnosed during the late first and early second trimesters, assess their association with additional brain and extracranial malformations, investigate their genetic etiologies and evaluate fetal outcomes.
METHODS: This retrospective, multicenter case series included fetuses with a diagnosis of GE cyst, following referral for targeted transvaginal ultrasound examination, before 23 + 0 weeks’ gestation at one of nine medical centers across eight countries between January 2015 and April 2023. All fetuses had been referred after either the first-trimester ultrasound screening examination or an early second-trimester anatomical scan diagnosed a GE cyst or raised suspicion of a cystic brain anomaly. All ultrasound images and three-dimensional ultrasound volumes for each case were retrieved and reviewed to identify brain and extracranial anomalies. Associated brain anomalies were classified into: cerebral midline; hemispheric parenchyma and lamination; lateral ventricles; sulcation pattern; and midbrain-hindbrain abnormalities. Genetic evaluations included chromosomal microarray analysis, exome sequencing and/or whole-genome sequencing, when available. Pregnancy outcomes and postnatal or autopsy data were reviewed when available.
RESULTS: In total, 25 fetuses with a diagnosis of GE cyst were included in the study. Cysts were bilateral in 64.0% of cases. In 36.0% of cases, the diagnosis was made between 11 + 3 and 13 + 6 weeks’ gestation. Additional brain abnormalities were identified in 18 of the 22 (81.8%) cases in which these were assessed. These included midline anomalies in 72.2% of those with additional brain abnormalities, hemispheric abnormalities in 77.8%, abnormalities of the lateral ventricles in 55.6%, midbrain-hindbrain abnormalities in 72.2% and sulcation abnormalities in 55.6%. Extracranial anomalies were present in 17/25 (68.0%) fetuses, of which fetal growth restriction was observed in 35.3%. Genetic testing revealed pathogenic or likely pathogenic variants in 70.6% of the 17 cases tested, predominantly affecting mitochondrial functions. The pregnancy was terminated in 64.0% of cases and the fetus was liveborn in 32.0%; one case was lost to follow-up during pregnancy. Of the seven surviving neonates with follow-up, five (71.4%) experienced adverse outcomes. Four of the 25 fetuses were initially diagnosed with an isolated unilateral GE cyst. In three of these cases, the cyst regressed and transformed into a GE enlargement, though their clinical courses differed: two cases developed growth restriction, of which one also had a postnatally repaired ventricular septal defect and the other a short femur length, and the third case had additional extracranial findings. In the fourth case, the cyst resolved completely, with an apparently normal brain observed at follow-up fetal magnetic resonance imaging.
CONCLUSIONS: Late first- or early second-trimester suspicion of GE cysts should trigger a transvaginal neurosonographic examination. The presence of early GE cysts appears to be associated with additional severe brain and extracranial anomalies, including fetal growth restriction. Comprehensive genetic testing is crucial for identifying underlying etiologies, which are often linked to mitochondrial dysfunction. © 2026 International Society of Ultrasound in Obstetrics and Gynecology.
PMID:41674274 | DOI:10.1002/uog.70180
