A rare intersection of Mood and Genetics: Fragile X Tremor Ataxia Syndrome (FXTAS) with Psychotic Depression
S. M. Toparlak, M. Hussain, P. MitterIntroduction
FXTAS is a neurodegenerative disorder seen in older premutation (55-200 CGG repeats) carriers of FMR1. Females may be less affected by FXTAS due to the presence of a second X chromosome that lacks the premutation. The prevalence of FXTAS is approximately 40% in male premutation carriers, while it remains significantly lower and rare in females, affecting only about 16% of female carriers. (Cabal-Herrera et al.,2020)
Psychiatric comorbidities in FXTAS were studied by researchers and found to be common. Chi et all. mentioned that even at early FXTAS stages, patients have significant cognitive and other psychiatric symptoms, with notable gender-specific differences.
Objectives
To describe a rare case of Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) presenting with psychotic depression, highlighting the intersection of genetic, neurological, and psychiatric domains.
Methods
The patient underwent comprehensive neuropsychiatric evaluation, including cognitive testing, MRI brain, and Fragile X premutation genetic analysis. Psychiatric symptoms were assessed using standard diagnostic criteria and managed with pharmacological and psychosocial interventions
Results
MRI (Magnetic Resonance Imaging) scan in 2016 showed global involutional change in advance of the patient’s age, which was requested due to difficulties with balance, falls, visual disturbance, history of severe depression and apathy. CT head scan in 2016 showed extra-axial spaces and ventricles being generally slightly prominent consistent with atrophy. In the same year, the 111 gene panel for retinal dystrophies revealed negative results. DAT (Dopamine Transporter Scan), SPECT (Single-photon emission computed tomography) /CT scan and nerve conduction studies in 2017 both reporting as normal with no evidence of dopaminergic synaptic loss. In July 2017, after comprehensive clinical assessment by the neurology team she was diagnosed with MSA type C (cerebellar form). However, a genetic testing in May 2023 confirmed FMR1 premutation, which, taken alongside her clinical syndrome of slowly progressive late onset tremor and ataxia. This resulted in her previous diagnosis of MSA type C to be revised into a diagnosis of Fragile X Tremor Ataxia Syndrome (FXTAS).
Image 1: Long description.