Aicardi Syndrome: Key Fetal MRI Features and Prenatal Differential Diagnosis

Masnada, Silvia; Doneda, Chiara; Izzo, Giana; Formica, Manuela; Scarabello, Marco; Accogli, Andrea; Accorsi, Patrizia; Bahi‐Buisson, Nadia; Capra, Valeria; Bernardo, Dalla Bernardina; Darra, Francesca; Valentina, De Giorgis; Fazzi, E.; Miguel, Fontanillas R L; Fusco, Carlo; Giordano, Lucio; Orcesi, Simona; Pinelli, Lorenzo; Rebessi, Erika; Romeo, Antonino; Severino, Mariasavina; Spagnoli, Carlotta; Veggiotti, Pierangelo; Pichiecchio, Anna; Righini, Andrea; Parazzini, Cecilia

doi:10.1055/s-0040-1710528

Cited by 3 publications

(1 citation statement)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When one considers that the AIC spectrum is wide and includes classical, likely and suspected cases, each with variable clinical and imaging phenotypes within each subgroup, it is likely that the genetic heterogeneity we identified is reflective of AIC not being a single malformation syndrome. Ongoing work to improve the phenotypic classification of AIC [ 70 , 71 ] are likely to assist with future attempts at gene identification.…”

Section: Discussionmentioning

confidence: 99%

Aicardi Syndrome Is a Genetically Heterogeneous Disorder

Ha,

Burgess,

Newman

et al. 2023

Genes

View full text Add to dashboard Cite

Aicardi Syndrome (AIC) is a rare neurodevelopmental disorder recognized by the classical triad of agenesis of the corpus callosum, chorioretinal lacunae and infantile epileptic spasms syndrome. The diagnostic criteria of AIC were revised in 2005 to include additional phenotypes that are frequently observed in this patient group. AIC has been traditionally considered as X-linked and male lethal because it almost exclusively affects females. Despite numerous genetic and genomic investigations on AIC, a unifying X-linked cause has not been identified. Here, we performed exome and genome sequencing of 10 females with AIC or suspected AIC based on current criteria. We identified a unique de novo variant, each in different genes: KMT2B, SLF1, SMARCB1, SZT2 and WNT8B, in five of these females. Notably, genomic analyses of coding and non-coding single nucleotide variants, short tandem repeats and structural variation highlighted a distinct lack of X-linked candidate genes. We assessed the likely pathogenicity of our candidate autosomal variants using the TOPflash assay for WNT8B and morpholino knockdown in zebrafish (Danio rerio) embryos for other candidates. We show expression of Wnt8b and Slf1 are restricted to clinically relevant cortical tissues during mouse development. Our findings suggest that AIC is genetically heterogeneous with implicated genes converging on molecular pathways central to cortical development.

show abstract

Section: Discussionmentioning

confidence: 99%

Aicardi Syndrome Is a Genetically Heterogeneous Disorder

Ha,

Burgess,

Newman

et al. 2023

Genes

View full text Add to dashboard Cite

show abstract

Prenatal diagnosis of Aicardi syndrome based on a suggestive imaging pattern: A multicenter case‐series

Pomar

Ochoa²,

Cabet

et al. 2022

Prenatal Diagnosis

View full text Add to dashboard Cite

Objectives To characterize a suggestive prenatal imaging pattern of Aicardi syndrome using ultrasound and MR imaging. Methods Based on a retrospective international series of Aicardi syndrome cases from tertiary centers encountered over a 20‐year period (2000–2020), we investigated the frequencies of the imaging features in order to characterize an imaging pattern highly suggestive of the diagnosis. Results Among 20 cases included, arachnoid cysts associated with a distortion of the interhemispheric fissure were constantly encountered associated with complete or partial agenesis of the corpus callosum (19/20, 95%). This triad in the presence of other CNS disorganization, such as polymicrogyria (16/17, 94%), heterotopias (15/17, 88%), ventriculomegaly (14/20, 70%), cerebral asymmetry [14/20, 70%]) and less frequently extra‐CNS anomaly (ocular anomalies [7/11, 64%], costal/vertebral segmentation defect [4/20, 20%]) represent a highly suggestive pattern of Aicardi syndrome in a female patient. Conclusion Despite absence of genetic test to confirm prenatal diagnosis of AS, this combination of CNS and extra‐CNS fetal findings allows delineation of a characteristic imaging pattern of AS, especially when facing dysgenesis of the corpus callosum.

show abstract

Basal Ganglia Dysmorphism in Patients With Aicardi Syndrome

Masnada¹,

Pichiecchio²,

Formica³

et al. 2021

Neurology

View full text Add to dashboard Cite

ObjectiveAiming 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.MethodsOnly 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.ResultsPatients 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).ConclusionThe 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 evidenceThis study provides Class II evidence that for patients with AIC, specific MRI abnormalities and EEG at onset are associated with clinical outcomes.

show abstract

Aicardi Syndrome: Key Fetal MRI Features and Prenatal Differential Diagnosis

Cited by 3 publications

References 24 publications

Aicardi Syndrome Is a Genetically Heterogeneous Disorder

Aicardi Syndrome Is a Genetically Heterogeneous Disorder

Prenatal diagnosis of Aicardi syndrome based on a suggestive imaging pattern: A multicenter case‐series

Basal Ganglia Dysmorphism in Patients With Aicardi Syndrome

Contact Info

Product

Resources

About