Journal Article Review Ahead of print
PubMed: 42611074 DOI: 10.1007/s00247-026-06747-3
Fetal magnetic resonance imaging features of syndromic megalencephaly: a systematic review of imaging-genotype associations.
Pediatr Radiol
Authors: Stephanie Libzon, Moran Hausman-Kedem, Nilly Waiserberg, Liat Ben Sira
Affiliations
- Pediatric Neurology Institute, Dana-Dwek Children's Hospital, Tel Aviv Sourasky University Medical Center (Ichilov), 6 Weizmann Street, Tel Aviv, 6423906, Israel.
- Gray Faculty of Medical and Health Science, Tel Aviv University, Tel Aviv, Israel.
- Pediatric Neurology Institute, Dana-Dwek Children's Hospital, Tel Aviv Sourasky University Medical Center (Ichilov), 6 Weizmann Street, Tel Aviv, 6423906, Israel.
- Gray Faculty of Medical and Health Science, Tel Aviv University, Tel Aviv, Israel.
- Department of Physical Therapy, School of Health Professions, Gray Faculty of Medical and Health Science, Tel Aviv University, Tel Aviv, Israel.
- Gray Faculty of Medical and Health Science, Tel Aviv University, Tel Aviv, Israel.
- Division of Pediatric Radiology, Department of Radiology, Dana-Dwek Children's Hospital, Tel Aviv Sourasky University Medical Center (Ichilov), 6 Weizmann Street, Tel Aviv, 6423906, Israel.
Abstract
Syndromic megalencephaly comprises a heterogeneous group of genetic disorders characterized by abnormal brain overgrowth and variable structural brain abnormalities. Prenatal recognition remains challenging because imaging findings overlap with those of isolated macrocephaly, while genotype-phenotype correlations are incompletely understood. This review summarizes the current literature on fetal magnetic resonance imaging (MRI) findings in molecularly confirmed syndromic megalencephaly and discusses their relationship with the underlying genetic pathways. The available evidence indicates that ventriculomegaly, malformations of cortical development, asymmetric lateral ventricles, hemimegalencephaly, and enlarged extra-axial spaces represent the most frequently reported prenatal MRI abnormalities, although their prevalence varies among genetic subgroups. Emerging imaging patterns suggest pathway-specific associations, particularly between the PIK3CA-AKT-mTOR pathway and hemimegalencephaly, and between RASopathies and enlarged extra-axial spaces. Current evidence is derived predominantly from case reports and small case series, underscoring the rarity of these disorders and the limited availability of systematic prenatal imaging data. Integrating fetal MRI findings with molecular diagnosis may improve prenatal diagnosis, facilitate targeted genetic testing, enhance prenatal counseling, and provide a foundation for future imaging-based diagnostic frameworks in syndromic megalencephaly.
MeSH
Radiotherapy, Megalencephaly, Brain, Magnetic Resonance Imaging, Radiography, Genotype, Diagnosis, Hemimegalencephaly