# A Boy with a Novel Variant in TCF20: An Expanded Phenotype and a Brief Review of the Literature

## TL;DR

A boy with a new TCF20 gene variant shows ADHD, motor issues, and brain malformation, highlighting the importance of genetic testing and MRI in diagnosing complex neurodevelopmental disorders.

## Contribution

Reports a novel TCF20 variant and expands the known phenotype of TCF20-NDD with Chiari I malformation and oculomotor dyspraxia.

## Key findings

- A de novo pathogenic frameshift variant in TCF20 was identified in an 11-year-old boy with neurodevelopmental symptoms.
- Chiari I malformation was observed in MRI scans, potentially linked to TCF20's role in cranial development.
- Exome sequencing and MRI are recommended for diagnosing unclear neurodevelopmental cases.

## Abstract

What are the main findings?

Chiari I Malformation.

Oculomotor dyspraxia.

What are the implications of the main findings?

Expanding neuroradiological findings in TCF20-NDD.

Exome sequencing is extremely important when the clinical picture is unclear.

Background: TCF20-associated neurodevelopmental disorder (TCF20-NDD) is a heterogeneous clinical condition resulting from defects in gene-encoding Transcription Factor 20, which plays a key role in neuronal development and synaptic function. Here, we present a novel case involving an 11-year-old boy who was referred to us for a neuro-developmental disorder characterized by attention deficit hyperactivity disorder (ADHD), tremor in the upper limbs, tilted head posture, motor delay, impaired executive functioning, and oculomotor dyspraxia. Methods: Genetic tests were performed, including CGH array, molecular analysis of the FMR1 gene, molecular analysis using a next-generation sequencing gene panel targeted for spinocerebellar diseases, and finally, WES including mitochondrial genome analysis. A neuroimaging study of brain and spine was performed using MRI. Results: Trio Whole Exome Sequencing revealed a de novo pathogenic frameshift variant NM_001378418.1:c.5009dup, p.(Thr1671Aspfs*5) in the TCF20 gene. The MRI scan of the brain, cervical, dorsal, and lumbosacral spine revealed Chiari type I malformation. Regarding the pathogenic mechanism underlying Chiari I malformation, it could be found in the homology between TCF20 and the RAI1 gene, the latter being associated with alterations in the posterior cranial fossa. Conclusions: We emphasize the use of exome sequencing in patients with unclear clinical presentations, with awareness of TCF20-associated neurodevelopmental disorder; paying attention to brain MRI findings would be useful to further expand the phenotype of TCF20-NDD.