Structural brain anomalies in patients with FOXG1 syndrome and in Foxg1+/− mice

Medientyp: E-Artikel
Titel: Structural brain anomalies in patients with FOXG1 syndrome and in Foxg1+/− mice
Beteiligte: Pringsheim, Milka; Mitter, Diana; Schröder, Simone; Warthemann, Rita; Plümacher, Kim; Kluger, Gerhard; Baethmann, Martina; Bast, Thomas; Braun, Sarah; Büttel, Hans‐Martin; Conover, Elizabeth; Courage, Carolina; Datta, Alexandre N.; Eger, Angelika; Grebe, Theresa A.; Hasse‐Wittmer, Annette; Heruth, Marion; Höft, Karen; Kaindl, Angela M.; Karch, Stephanie; Kautzky, Torsten; Korenke, Georg C.; Kruse, Bernd; Lutz, Richard E.; [...]
Erschienen: Wiley, 2019
Erschienen in: Annals of Clinical and Translational Neurology
Sprache: Englisch
DOI: 10.1002/acn3.735
ISSN: 2328-9503
Schlagwörter: Neurology (clinical) ; General Neuroscience
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Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p><jats:styled-content style="fixed-case">FOXG</jats:styled-content>1 syndrome is a rare neurodevelopmental disorder associated with heterozygous <jats:italic><jats:styled-content style="fixed-case">FOXG</jats:styled-content>1</jats:italic> variants or chromosomal microaberrations in 14q12. The study aimed at assessing the scope of structural cerebral anomalies revealed by neuroimaging to delineate the genotype and neuroimaging phenotype associations.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We compiled 34 patients with a heterozygous (likely) pathogenic <jats:italic><jats:styled-content style="fixed-case">FOXG</jats:styled-content>1</jats:italic> variant. Qualitative assessment of cerebral anomalies was performed by standardized re‐analysis of all 34 <jats:styled-content style="fixed-case">MRI</jats:styled-content> data sets. Statistical analysis of genetic, clinical and neuroimaging data were performed. We quantified clinical and neuroimaging phenotypes using severity scores. Telencephalic phenotypes of adult <jats:italic>Foxg1</jats:italic>+/− mice were examined using immunohistological stainings followed by quantitative evaluation of structural anomalies.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Characteristic neuroimaging features included corpus callosum anomalies (82%), thickening of the fornix (74%), simplified gyral pattern (56%), enlargement of inner <jats:styled-content style="fixed-case">CSF</jats:styled-content> spaces (44%), hypoplasia of basal ganglia (38%), and hypoplasia of frontal lobes (29%). We observed a marked, filiform thinning of the rostrum as recurrent highly typical pattern of corpus callosum anomaly in combination with distinct thickening of the fornix as a characteristic feature. Thickening of the fornices was not reported previously in <jats:styled-content style="fixed-case">FOXG</jats:styled-content>1 syndrome. Simplified gyral pattern occurred significantly more frequently in patients with early truncating variants. Higher clinical severity scores were significantly associated with higher neuroimaging severity scores. Modeling of <jats:italic>Foxg1</jats:italic> heterozygosity in mouse brain recapitulated the associated abnormal cerebral morphology phenotypes, including the striking enlargement of the fornix.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>Combination of specific corpus callosum anomalies with simplified gyral pattern and hyperplasia of the fornices is highly characteristic for <jats:styled-content style="fixed-case">FOXG</jats:styled-content>1 syndrome.</jats:p></jats:sec>
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