Neuroimaging aspects of Aicardi syndrome

Abstract

Aicardi syndrome is a rare neurodevelopmental disorder characterized by congenital chorioretinal lacunae, corpus callosum dysgenesis, seizures, polymicrogyria, cerebral heterotopias, intracranial cysts, and costovertebral defects. Cerebellar abnormalities have been described occasionally. Aicardi syndrome is sporadic and has been observed only in females and 47,XXY males. Therefore, it is thought to result from a mutation in an X-linked gene. Improved definition of the clinical phenotype should focus the selection of functional candidate genes for mutation analysis. Because central nervous system abnormalities are the most prominent component of the phenotype, we performed a detailed characterization of abnormalities identified on magnetic resonance neuroimaging studies from 23 girls with Aicardi syndrome, the largest cohort to undergo such review by a single group of investigators. All patients had polymicrogyria that was predominantly frontal and perisylvian and often associated with underopercularization. Periventricular nodular heterotopias, present in all patients, were more frequent than previously reported; 10 had single and 11 had multiple intracranial cysts. Posterior fossa abnormalities were also more frequent than previously described. Cerebellar abnormalities were noted in 95% of studies where they could be evaluated. As a novel finding, we noted tectal enlargement in 10 patients. Since mildly-affected girls with variable callosal dysgenesis have now been reported, the constellation of frontal-dominant and perisylvian polymicrogyria, periventricular nodular heterotopias, intracranial cysts, and posterior fossa abnormalities, including tectal enlargement, should prompt consideration of the diagnosis of Aicardi syndrome. We further propose that improved characterization of the neurological phenotype will benefit the selection of candidate genes for mutation analysis.

Serial Fetal MRI for the Diagnosis of Aicardi Syndrome

“…Callosal agenesis is complete in about 70% and partial in 30% of AS patients 3 . The outcome seems to be more favorable in AS patients with partial compared to those with complete corpus callosum agenesis 25 .…”

“…The outcome seems to be more favorable in AS patients with partial compared to those with complete corpus callosum agenesis 25 . The additional findings in AS may show a wide variability including polymicrogyria and heterotopias, intracranial cysts, posterior fossa abnormalities such as hypoplasia and/or dysplasia of the cerebellar hemispheres, heterotopias, cerebellar cysts and tectal enlargement and sometimes choroid plexus papillomas 2,3 . Consequently, the prognosis differs significantly.…”

“…The outcome in AS is usually poor with considerable morbidity including severe intellectual disability and therapy-resistant seizures, and high early mortality 2 . Additional neuroimaging findings include ventriculomegaly with colpocephaly, polymicrogyria, periventricular and subcortical heterotopias, intracranial cysts and cerebellar abnormalities 3 . We report on serial prenatal magnetic resonance imaging (MRI) studies in a female fetus with AS.…”

Cerebellar Cysts in Children: a Pattern Recognition Approach

“…2). Cerebellar abnormalities are overall frequent including inferior vermis hypoplasia, dysplastic or hypoplastic hemispheres, and subcortical and periventricular heterotopias [21]. In the series reported by Hopkins et al, cysts were present in 4/23 girls [21].…”

Aicardi Syndrome Associated with Autosomal Genomic Imbalance: Coincidence or Evidence for Autosomal Inheritance with Sex-Limited Expression?

“…Revised criteria include: characteristic facial features, such as prominent premaxilla, upturned nasal tip, decreased angle of the nasal bridge, sparse lateral eyebrows, coloboma of the optic nerve, in addition to the chorioretinal lacunae, microcephaly, periventricular heterotopias, microgyria, enlarged ventricles or porencephalic cysts. Moreover, moderate-to-severe developmental delay and intellectual disability is found in almost all patients [Aicardi et al, 1965;Bertoni et al, 1979;Aicardi, 1999Aicardi, , 2005 Roser, 2003;Sutton et al, 2005;Hopkins et al, 2008].The etiology of AIS is still unknown, even if a genetic etiology due to a de novo X-linked dominant mutation lethal in hemizygous male embryos is strongly suspected [Wettke-Schäfer and Kanter, 1983; Donnenfeld et al, …”