Recognisable Neuroradiological Findings in Five Neurogenetic Disorders

• Published in: Clinical genetics 2025-01, Vol.107 (1), p.13-22
• Main Authors: Rosenblum, Jessica, Meuwissen, Marije, Jansen, Anna C., Oegema, Renske, Reddy, Nihaal, Mankad, Kshitij, Sudhakar, Sniya
• Format: Article
• Language: English
• Subjects: ARFGEF2; Brain - diagnostic imaging; Brain - pathology; DDX3X; diagnostic imaging; EML1; Genetic variability; Glutamate receptors; Guanine Nucleotide Exchange Factors - genetics; Humans; Magnetic Resonance Imaging; Microencephaly; Molecular modelling; N-Methyl-D-aspartic acid receptors; Neurodevelopmental disorders; Neurodevelopmental Disorders - diagnostic imaging; Neurodevelopmental Disorders - genetics; Neurodevelopmental Disorders - pathology; Neuroimaging; Neuroimaging - methods; N‐methyl‐D‐aspartate receptors; Pediatrics; Phenotype; Phenotypes; Van Maldergem syndrome; Ventricle (lateral)
• ISSN: 0009-9163; 1399-0004; 1399-0004
• DOI: 10.1111/cge.14637

ABSTRACT The rate of discovery and increased understanding of genetic causes for neurodevelopmental disorders has peaked over the past decade. It is well recognised that some genes show marked variability in neuroradiological phenotypes, and inversely, some radiological phenotypes are associated with several different genetic conditions. However, some readily recognisable brain magnetic resonance imaging (MRI) patterns, especially in the context of corresponding associated clinical findings, should prompt consideration of a pathogenic variant in a specific gene or gene pathway. As these conditions can often prove challenging to diagnose, a clinical suspicion of a specific disorder may be invaluable to guide and interpret genetic testing. This review focuses on five neurogenetic syndromes with recognisable brain findings that radiologists, paediatric neurologists, geneticists, and other specialists involved in neurodevelopmental disorders should be able to recognise in order to pinpoint the gene or gene groups involved and delve into their molecular mechanisms. The comprehensively reviewed conditions include DDX3X‐related neurodevelopmental disorder, Van Maldergem syndrome, NMDAR‐related disorders, EML1‐associated disorder and ARFGEF2‐related periventricular nodular heterotopia with microcephaly. This review delves into five rare neurogenetic disorders characterised by distinct neuroradiological patterns, aiding healthcare providers in identifying these syndromes. Recognising these imaging features can facilitate diagnosis, guide genetic testing and improve clinical management and family counselling for neurodevelopmental disorders.