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Objective This study was aimed to investigate the prenatal findings in Aicardi syndrome (AIC) by intrauterine magnetic resonance imaging (iuMRI) suggesting possible diagnostic criteria and differential diagnosis. Methods The iuMRI features of nine AIC confirmed cases were described and then compared with those of postnatal MRI. Furthermore, all iuMRI cases with both corpus callosum (CC) agenesis–dysgenesis and cortical malformation (AIC mimickers) were retrospectively reviewed and compared with iuMRI AIC cases, in order to identify possible neuroradiological predictors of AIC syndrome. For this purpose, Chi-square statistic and binary logistic regression analysis were performed. Results In all AIC cases, iuMRI was able to detect CC agenesis–dysgenesis and cortical development anomalies. Postnatal MRI revealed some additional findings mainly including further cystic lesions and in two cases small coloboma. A statistically significant difference between AIC and AIC mimicker were found regarding sex, nodular heterotopias, posterior fossa abnormalities, coloboma, and cortical gyration abnormalities. The most predictive variables in the logistic regression model were cortical gyration abnormalities, coloboma, and sex. Conclusion The iuMRI findings may suggest prenatal diagnosis of AIC syndrome with significant impact on parental counseling. Among possible differential diagnoses, tubulinopathies emerged.

Objective Aiming to detect associations between neuroradiologic and EEG evaluations and long-term clinical outcome in order to detect possible prognostic factors, a detailed clinical and neuroimaging characterization of 67 cases of Aicardi syndrome (AIC), collected through a multicenter collaboration, was performed. Methods Only patients who satisfied Sutton diagnostic criteria were included. Clinical outcome was assessed using gross motor function, manual ability, and eating and drinking ability classification systems. Brain imaging studies and statistical analysis were reviewed. Results Patients presented early-onset epilepsy, which evolved into drug-resistant seizures. AIC has a variable clinical course, leading to permanent disability in most cases; nevertheless, some cases presented residual motor abilities. Chorioretinal lacunae were present in 86.56 EEG at onset, and clinical outcome. On brain imaging, 100 98 and 96.36with similar rates of 2b and 2d). As well as demonstrating that posterior fossa abnormalities (found in 63.63 should also be considered a common feature in AIC, our study highlighted the presence (in 76.36 of basal ganglia dysmorphisms (never previously reported). Conclusion The AIC neuroradiologic phenotype consists of a complex brain malformation whose presence should be considered central to the diagnosis. Basal ganglia dysmorphisms are frequently associated. Our work underlines the importance of MRI and EEG, both for correct diagnosis and as a factor for predicting long-term outcome. Classification of Evidence This study provides Class II evidence that for patients with AIC, specific MRI abnormalities and EEG at onset are associated with clinical outcomes. Objective Aiming to detect associations between neuroradiologic and EEG evaluations and long-term clinical outcome in order to detect possible prognostic factors, a detailed clinical and neuroimaging characterization of 67 cases of Aicardi syndrome (AIC), collected through a multicenter collaboration, was performed.Methods Only patients who satisfied Sutton diagnostic criteria were included. Clinical outcome was assessed using gross motor function, manual ability, and eating and drinking ability classification systems. Brain imaging studies and statistical analysis were reviewed.Results Patients presented early-onset epilepsy, which evolved into drug-resistant seizures. AIC has a variable clinical course, leading to permanent disability in most cases; nevertheless, some cases presented residual motor abilities. Chorioretinal lacunae were present in 86.56% of our patients. Statistical analysis revealed correlations between MRI, EEG at onset, and clinical outcome. On brain imaging, 100% of the patients displayed corpus callosum malformations, 98% cortical dysplasia and nodular heterotopias, and 96.36% intracranial cysts (with similar rates of 2b and 2d). As well as demonstrating that posterior fossa abnormalities (found in 63.63% of cases) should also be considered a common feature in AIC, our study highlighted the presence (in 76.36%) of basal ganglia dysmorphisms (never previously reported).Conclusion The AIC neuroradiologic phenotype consists of a complex brain malformation whose presence should be considered central to the diagnosis. Basal ganglia dysmorphisms are frequently associated. Our work underlines the importance of MRI and EEG, both for correct diagnosis and as a factor for predicting long-term outcome.Classification of Evidence This study provides Class II evidence that for patients with AIC, specific MRI abnormalities and EEG at onset are associated with clinical outcomes.

Objective To provide new insights into the FOXG1-related clinical and imaging phenotypes and refine the phenotype-genotype correlation in FOXG1 syndrome. Methods We analyzed the clinical and imaging phenotypes of a cohort of 45 patients with a pathogenic or likely pathogenic FOXG1 variant and performed phenotype-genotype correlations. Results A total of 37 FOXG1 different heterozygous mutations were identified, of which 18 are novel. We described a broad spectrum of neurodevelopmental phenotypes, characterized by severe postnatal microcephaly and developmental delay accompanied by a hyperkinetic movement disorder, stereotypes and sleep disorders, and epileptic seizures. Our data highlighted 3 patterns of gyration, including frontal pachygyria in younger patients (26.7%), moderate simplified gyration (24.4%) and mildly simplified or normal gyration (48.9%), corpus callosum hypogenesis mostly in its frontal part, combined with moderate-to-severe myelination delay that improved and normalized with age. Frameshift and nonsense mutations in the N-terminus of FOXG1, which are the most common mutation types, show the most severe clinical features and MRI anomalies. However, patients with recurrent frameshift mutations c.460dupG and c.256dupC had variable clinical and imaging presentations. Conclusions These findings have implications for genetic counseling, providing evidence that N-terminal mutations and large deletions lead to more severe FOXG1 syndrome, although genotype-phenotype correlations are not necessarily straightforward in recurrent mutations. Together, these analyses support the view that FOXG1 syndrome is a specific disorder characterized by frontal pachygyria and delayed myelination in its most severe form and hypogenetic corpus callosum in its milder form.