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. 2019 Jun 28:10:641.
doi: 10.3389/fneur.2019.00641. eCollection 2019.

Cognition and Evolution of Movement Disorders of FOXG1-Related Syndrome

Lee-Chin Wong  1   2 , Yen-Tzu Wu  3   4 , Chia-Jui Hsu  5 , Wen-Chin Weng  6 , Wen-Che Tsai  7 , Wang-Tso Lee  6   8
Affiliations

Cognition and Evolution of Movement Disorders of FOXG1-Related Syndrome

Lee-Chin Wong et al. Front Neurol. .

Abstract

FOXG1-related syndrome is a rare neurodevelopmental encephalopathy characterized by early onset hyperkinetic movement disorders, absent language, autistic features, epilepsy, and severe cognitive impairment. However, detailed evaluation of cognition and evolution of movement disorders over time have not been clearly described before. In this study, we performed whole-exome sequencing in a cohort with unknown severe encephalopathy and movement disorders, with/without autistic behaviors. We identified FOXG1 mutations in three patients. One of them had a novel mutation that has not been described before. The neuropsychological test by Mullen Scales of Early Learning (MSEL) showed severe psychomotor impairments in all patients. There were uneven cognitive abilities in terms of verbal and non-verbal cognitive domains in all of them, with approximately 2 months differences. Gross motor skills and expressive language were more severely affected than the other domains in all the patients. All individuals had early onset hyperkinetic movement disorders. The movement disorders in one of our patients changed from predominantly hyperkinetic in early childhood to more hypokinetic in adolescence with the development of dystonia. To the best of our knowledge, this evolution had never been described before. In conclusion, individuals with FOXG1-related syndrome may show clinical progression from hyperkinetic to hypokinetic features over time. There were also uneven cognitive abilities in verbal and non-verbal cognitive domains. The FOXG1 mutation should be considered in individuals with a history of hyperkinetic movements, microcephaly, and uneven cognitive abilities with characteristic brain images.

Keywords: FOXG1; cognition; evolution; hyperkinetic; hypokinetic; movement disorder.

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Figures

Figure 1
Figure 1
Schematic representation of the FOXG1 protein (consisting of 489 amino acid) and the mutations of our patients. The N-terminal domain, fork-head domain, the Groucho-binding domain (GBD), the JARID1B binding domain (JBD), and C-terminal domain of FOXG1 are shown.
Figure 2
Figure 2
T1 and T2 MRI images of case 1 (A-C) at 6 months of age, case 2 (D-F) at 7 years of age, and case 3 (G-I) at 11 months of age showed dysgenesis of the corpus callosum, including the genu and body portions of the corpus callosum.
See this image and copyright information in PMC

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