Intractable Rare Dis Res. 2020;9(2):113-118. (DOI: 10.5582/irdr.2020.01028)

Fragile X associated neuropsychiatric disorders in a male without FXTAS

Cabal-Herrera AM, Saldarriaga-Gil W, Salcedo-Arellano MJ, Hagerman RJ


Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and autism spectrum disorder. In most cases, it is due to an expansion of the CGG triplet to more than 200 repeats within the promoter region of the FMR1 gene. In the premutation (PM) the trinucleotide is expanded to 55-200 repeats. PM carriers can present with disorders associated with the PM including fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X-associated ovarian insufficiency (FXPOI). Recently fragile X-associated neuropsychiatric disorders (FXAND) was proposed as an umbrella term to include the neuropsychiatric disorders that are more prevalent in PM carriers compared to the general population such as anxiety, depression, chronic fatigue, alcohol abuse, and psychosis, among others. The patient in our study was evaluated by a team of clinicians from the University del Valle in Cali who traveled to Ricaurte, a Colombian town known for being a genetic geographic cluster of FXS. A detailed medical history was collected and complete physical, neurological and psychiatric evaluations were performed in addition to molecular and neuroradiological studies. We report the case of a 78-year-old man, PM carrier, without FXTAS whose main clinical presentation consists of behavioral changes and psychosis. Brain imaging revealed white matter lesions in the periventricular region and mild cerebral atrophy. Although anxiety and depression are the most common neuropsychiatric manifestations in PM carriers, it is important to perform a complete psychiatric evaluation since some patients may present with behavioral changes and psychosis.

KEYWORDS: fragile X mental retardation 1 gene, fragile X-associated neuropsychiatric disorders, premutation, FXAND, psychosis

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