FXAND is a proposed umbrella term that represents the neuropsychiatric conditions associated with fragile X premutation carriers. It is not limited to one entity but includes various neuropsychiatric disorders. It primarily presents as neuropsychiatric symptoms in premutation carriers who do not have the clinical signs of FXTAS, such as significant action tremor and/or cerebellar ataxia, in addition to white matter disease on MRI and white matter hyperintensities in the middle cerebellar peduncles. Neuropsychiatric problems in FXAND emerge before the neurological problems develop in FXTAS and onset is typically at an earlier age.
The diagnosis of FXAND requires FMR1 DNA testing to identify if one is a premutation carrier (55–200 CGG repeats), and a psychiatric evaluation to determine the presence of a neuropsychiatric disorder. These, along with genetic counseling, can guide treatment. Timely diagnosis is crucial due to the premutation carrier’s likelihood of developing the co-morbidities discussed here, as well as having children with an FMR1 mutation and accompanying neuropsychiatric or neurodevelopmental disorders. Conversely, individuals presenting with mood or anxiety disorders and a family history of FXS, developmental delay, intellectual disability or autism spectrum disorder should also be screened.
Randi Hagerman
