<i>FOXG1</i>-Related Syndrome: From Clinical to Molecular Genetics and Pathogenic Mechanisms

• Main Authors: Lee-Chin Wong, Shekhar Singh, Hsin-Pei Wang, Chia-Jui Hsu, Su-Ching Hu, Wang-Tso Lee
• Format: Article
• Language: English
• Published: MDPI AG 2019-08-01
• Series: International Journal of Molecular Sciences
• Subjects: <i>FOXG1</i>; Rett syndrome; hyperkinetic movements; telencephalon; transcriptional factor
• Online Access: https://www.mdpi.com/1422-0067/20/17/4176

Individuals with mutations in forkhead box G1 (<i>FOXG1</i>) belong to a distinct clinical entity, termed &#8220;<i>FOXG1</i>-related encephalopathy&#8221;. There are two clinical phenotypes/syndromes identified in <i>FOXG1</i>-related encephalopathy, duplications and deletions/intragenic mutations. In children with deletions or intragenic mutations of <i>FOXG1</i>, 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 <i>FOXG1</i> 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 <i>FOXG1</i>-related syndrome.