Klinik für Neuropädiatrie und Neurologische Rehabilitation Epilepsiezentrum für Kinder und Jugendliche Schön Klinik Vogtareuth Vogtareuth Germany.
Research Institute "Rehabilitation, Transition, Rehabilitation" Paracelsus Medical University Salzburg Austria.
Ann Clin Transl Neurol. 2019 Mar 3;6(4):655-668. doi: 10.1002/acn3.735. eCollection 2019 Apr.
FOXG1 syndrome is a rare neurodevelopmental disorder associated with heterozygous 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.
We compiled 34 patients with a heterozygous (likely) pathogenic variant. Qualitative assessment of cerebral anomalies was performed by standardized re-analysis of all 34 MRI 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 +/- mice were examined using immunohistological stainings followed by quantitative evaluation of structural anomalies.
Characteristic neuroimaging features included corpus callosum anomalies (82%), thickening of the fornix (74%), simplified gyral pattern (56%), enlargement of inner CSF 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 FOXG1 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 heterozygosity in mouse brain recapitulated the associated abnormal cerebral morphology phenotypes, including the striking enlargement of the fornix.
Combination of specific corpus callosum anomalies with simplified gyral pattern and hyperplasia of the fornices is highly characteristic for FOXG1 syndrome.
FOXG1 综合征是一种罕见的神经发育障碍，与 14q12 上的杂合变异或染色体微缺失有关。本研究旨在评估神经影像学揭示的结构性脑异常范围，以描绘基因型和神经影像学表型的相关性。
我们汇编了 34 名携带杂合（可能）致病性变异的患者。通过对所有 34 个 MRI 数据集进行标准化重新分析，对脑异常进行定性评估。对遗传、临床和神经影像学数据进行统计分析。我们使用严重程度评分来量化临床和神经影像学表型。使用免疫组织化学染色和结构异常的定量评估，研究成年 +/- 小鼠的端脑表型。
特征性神经影像学特征包括胼胝体异常（82%）、穹窿增厚（74%）、脑回简化（56%）、内脑脊髓液空间扩大（44%）、基底节发育不良（38%）和额叶发育不良（29%）。我们观察到一种明显的、丝状变薄的胼胝体，作为胼胝体异常的高度典型的复发性模式，与穹窿明显增厚相结合，作为特征性特征。此前在 FOXG1 综合征中未报道过穹窿增厚。脑回简化模式在具有早期截断变异的患者中更频繁发生。较高的临床严重程度评分与较高的神经影像学严重程度评分显著相关。在小鼠脑中模拟杂合性，重现了相关的异常大脑形态表型，包括穹窿的明显增大。
特定的胼胝体异常与脑回简化模式和穹窿增生的组合对 FOXG1 综合征具有高度特征性。
