The FMR1 gene premutation (55-200 CGG repeats) is usually associated with a wide range of symptoms and phenotypes within the Fragile X-tremor/ataxia syndrome (FXTAS), but may also manifest as predominant or isolated cognitive decline. We describe three male patients referred for progressive cognitive impairment and behavioral changes. Standard work-up, including MRI, FDG-PET, CSF biomarkers, and neuropsychological testing, excluded common dementias. Brain MRI imaging revealed callosal and peduncular white matter changes, while 18FDG-PET showed consistent anterior cingulate hypometabolism. Genetic analysis confirmed FMR1 premutation in all cases. Clinicians in memory clinics should consider this diagnosis in cases of unexplained cognitive decline.
Greco, G., Motta, C., Marchionni, E., D'Apice, M.r., Carrese, C., Novelli, G., et al. (2026). An Out-of-Place Etiology: Recognizing FMR1 Premutation in the Memory Clinic. ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY, 13(3), 607-611 [10.1002/acn3.70286].
An Out-of-Place Etiology: Recognizing FMR1 Premutation in the Memory Clinic
Motta C.;Marchionni E.;D'Apice M. R.;Carrese C.;Novelli G.;Martorana A.;Bonomi C. G.
2026-01-01
Abstract
The FMR1 gene premutation (55-200 CGG repeats) is usually associated with a wide range of symptoms and phenotypes within the Fragile X-tremor/ataxia syndrome (FXTAS), but may also manifest as predominant or isolated cognitive decline. We describe three male patients referred for progressive cognitive impairment and behavioral changes. Standard work-up, including MRI, FDG-PET, CSF biomarkers, and neuropsychological testing, excluded common dementias. Brain MRI imaging revealed callosal and peduncular white matter changes, while 18FDG-PET showed consistent anterior cingulate hypometabolism. Genetic analysis confirmed FMR1 premutation in all cases. Clinicians in memory clinics should consider this diagnosis in cases of unexplained cognitive decline.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
