Molecular and synaptic defects in intellectual disability syndromes

The search for genetic causes of intellectual disability has identified, over the past twenty years, numerous mutated genes that code for proteins concerned with synapse function. Functional studies have shown that these genes may be involved in synapse formation, the synthesis and degradation of specific synapse proteins, the regulation of dendritic spine morphology, or regulation of the synaptic cytoskeleton. It is now clear that even mild alterations in synapse morphology and function can give rise to intellectual disability, and pharmacological agents able to counteract these morphological and functional anomalies - and improve the symptoms of some of these conditions - now appear feasible. This paper reviews recent findings on the functions of some of the genes responsible for intellectual disability syndromes.

► We summarized recent findings that describe the function of four X-linked ID genes: IL1RAPL1, Oligophrenin1, FMRP and MeCP2. ► We described the multiple functions of the major scaffold protein Shank3 which mutations have been clearly associated to ID. ► We underlined some new therapeutic prospects for ID.