Towards an Understanding of Neuropsychiatric Manifestations in Fragile X Premutation Carriers.

Abstract

Fragile X-associated disorders (FXD) are a group of disorders caused by expansion of non-coding CGG repeat elements in the fragile X (FMR1) gene. One of these disorders, fragile X syndrome (FXS), is the most common heritable cause of intellectual disability, and is caused by large CGG repeat expansions (>200) resulting in silencing of the FMR1 gene. An increasingly recognized number of neuropsychiatric FXD have recently been identified that are caused by 'premutation' range expansions (55-200). These disorders are characterized by a spectrum of neuropsychiatric manifestations ranging from an increased risk of neurodevelopmental, mood and anxiety disorders to neurodegenerative phenotypes such as the fragile X-associated tremor ataxia syndrome (FXTAS). Here, we review advances in the clinical understanding of neuropsychiatric disorders in premutation carriers across the lifespan and offer guidance for the detection of such disorders by practicing psychiatrists and neurologists.