FOXG1-related syndrome: From clinical to molecular genetics and pathogenic mechanisms
Journal
International Journal of Molecular Sciences
Journal Volume
20
Journal Issue
17
Pages
4176
Date Issued
2019
Author(s)
Abstract
Individuals with mutations in forkhead box G1 (FOXG1) belong to a distinct clinical entity, termed " FOXG1-related encephalopathy” . There are two clinical phenotypes/syndromes identified in FOXG1-related encephalopathy, duplications and deletions/intragenic mutations. In children with deletions or intragenic mutations of FOXG1, the recognized clinical features include microcephaly, developmental delay, severe cognitive disabilities, early-onset dyskinesia and hyperkinetic movements, stereotypies, epilepsy, and cerebral malformation. In contrast, children with duplications of FOXG1 are typically normocephalic and have normal brain magnetic resonance imaging. They also have different clinical characteristics in terms of epilepsy, movement disorders, and neurodevelopment compared with children with deletions or intragenic mutations. FOXG1 is a transcriptional factor. It is expressed mainly in the telencephalon and plays a pleiotropic role in the development of the brain. It is a key player in development and territorial specification of the anterior brain. In addition, it maintains the expansion of the neural proliferating pool, and also regulates the pace of neocortical neuronogenic progression. It also facilitates cortical layer and corpus callosum formation. Furthermore, it promotes dendrite elongation and maintains neural plasticity, including dendritic arborization and spine densities in mature neurons. In this review, we summarize the clinical features, molecular genetics, and possible pathogenesis of FOXG1-related syndrome. ? 2019 by the authors. Licensee MDPI, Basel, Switzerland.
SDGs
Other Subjects
BMI1 protein; corticotropin; forkhead box G1; forkhead transcription factor; levodopa; Smad2 protein; Smad4 protein; sonic hedgehog protein; tetrabenazine; transforming growth factor beta; unclassified drug; biological marker; forkhead transcription factor; FOXG1 protein, human; nerve protein; brain disease; carcinogenesis; choreoathetosis; cognitive defect; developmental delay; electroencephalogram; epilepsy; epileptic discharge; focal epilepsy; FOXG1 syndrome; gastroesophageal reflux; gene deletion; gene insertion; gene mutation; genotype; genotype phenotype correlation; hormonal therapy; human; hyperkinesia; infantile spasm; Lennox Gastaut syndrome; loss of function mutation; macrogyria; mental disease; microcephaly; muscle hypotonia; nervous system development; nonhuman; nonsense mutation; Notch signaling; nuclear magnetic resonance imaging; Review; stereotypy; visual impairment; brain disease; gene duplication; genetic association study; genetic predisposition; genetic variation; genetics; mutation; neuroimaging; phenotype; procedures; Rett syndrome; Biomarkers; Brain Diseases; Forkhead Transcription Factors; Gene Duplication; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Humans; Mutation; Nerve Tissue Proteins; Neuroimaging; Phenotype; Rett Syndrome
Publisher
MDPI AG
Type
review