Neurophysiological markers that links genes and behavior in humans: examples from rare genetic syndromes associated with autism spectrum disorders

Abstract

This article introduces the concept of a neurophysiological profile, which combines non-invasive neurophysiological markers in relation with molecular genetic characteristics and behavioral features. The development and implementation of this approach still requires efforts, but the examples of rare genetic syndromes associated with autism spectrum disorder presented in the article show the direction of movement. For the recently discovered Potoky-Lupski syndrome associated with disturbances in the 17p11.2 zone, a previously undescribed epileptiform activity was detected - saw-like hypersynchronization at a frequency of 13 Hz, which may indicate a certain type of disturbance in the excitation/inhibition balance in neural networks. For a rare case of microduplication in the SHANK3 gene, also associated with the Phelan-McDermid syndrome, a pathway from a violation in the functioning of the SHANK3 protein, through a distorted interaction of excitatory and inhibitory neurons, primarily associated with hypofunction of NMDA receptors on inhibitory neurons, to reduced temporal resolution auditory cortex, reflecting in the absence of response following 40 Hz auditory stimulation (40 Hz auditory steady-state response) and underlying problems in speech development was described. For Rett syndrome, which is caused by a mutation in the MECP2 gene, which has a very wide influence on many other genes, the neurophysiological findings are also diverse. Among the most promising are changes in sensorimotor rhythm, potentially associated with a key symptom of the disease - stereotyped hand movements, as well as more delayed latency of the main components of the event-related potentials, which can have a cascading effect on information processing and affect the perception of basic information, including speech. The results presented here can help not only to objectify the diagnosis of developmental disorders, but also to build a mechanistic chain from gene to behavior.