Key role of Rho GTPases in motor disorders associated with neurodevelopmental pathologies.

This research review looks at special proteins in the brain that help control movement and thinking. Scientists found that problems with these proteins can cause both movement difficulties and thinking challenges in children with autism and other developmental conditions. The study shows that movement problems and thinking problems often happen together, and early movement difficulties can affect a child's ability to communicate and learn.

This comprehensive review examines the role of Rho GTPases (cellular signaling proteins) in motor disorders associated with neurodevelopmental conditions. The authors highlight that motor symptoms, ranging from mild to severe, are increasingly recognized in autism and other cognitive neurodevelopmental disorders. Through analysis of genetic mutations and whole exome sequencing data, the review demonstrates that Rho GTPases are crucial for both cognitive development and motor circuit formation in the brain. The paper emphasizes the interconnected nature of motor and cognitive development, noting that early motor impairments often impact social communication, cognition, emotion, and behavior in various neurodevelopmental conditions including autism spectrum disorders.

This review supports the importance of comprehensive motor assessment in neurodevelopmental disorders, particularly autism. It suggests that motor difficulties may be an early indicator requiring intervention, as they can impact broader developmental domains including communication and behavior.

As a narrative review, this study does not provide systematic analysis of evidence quality or quantitative synthesis of findings. The specific clinical implications and therapeutic targets require further empirical validation through controlled studies.

Growing evidence suggests that Rho GTPases and molecules involved in their signaling pathways play a major role in the development of the central nervous system (CNS). Whole exome sequencing (WES) and de novo examination of mutations, including SNP (Single Nucleotide Polymorphism) in genes coding for the molecules of their signaling cascade, has allowed the recent discovery of dominant autosomic mutations and duplication or deletion of candidates in the field of neurodevelopmental diseases (NDD). Epidemiological studies show that the co-occurrence of several of these neurological pathologies may indeed be the rule. The regulators of Rho GTPases have often been considered for cognitive diseases such as intellectual disability (ID) and autism.

But, in a remarkable way, mild to severe motor symptoms are now reported in autism and other cognitive NDD. Although a more abundant litterature reports the involvement of Rho GTPases and signaling partners in cognitive development, molecular investigations on their roles in central nervous system (CNS) development or degenerative CNS pathologies also reveal their role in embryonic and perinatal motor wiring through axon guidance and later in synaptic plasticity. Thus, Rho family small GTPases have been revealed to play a key role in brain functions including learning and memory but their precise role in motor development and associated symptoms in NDD has been poorly scoped so far, despite increasing clinical data highlighting the links between cognition and motor development. Indeed, early impairements in fine or gross motor performance is often an associated feature of NDDs, which then impact social communication, cognition, emotion, and behavior.

We review here recent insights derived from clinical developmental neurobiology in the field of Rho GTPases and NDD (autism spectrum related disorder (ASD), ID, schizophrenia, hypotonia, spastic paraplegia, bipolar disorder and dyslexia), with a specific focus on genetic alterations affecting Rho GTPases that are involved in motor circuit development.