Fragile X-associated tremor/ataxia syndrome masquerading as Normal Pressure Hydrocephalus- a report with clinical radiological and genetic correlation
Abstract
Background: Normal pressure hydrocephalus is a relatively common cause of treatable dementia in elderly, where patients are presented with triad of gait disturbances, urinary incontinence and dementia. Fragile X tremor ataxia syndrome(FXTAS) is an inherited X-linked dominant disorder due to CGG trinucleotide repeat expansion of the FMR1 gene. Usually presents with progressive cerebellar ataxia, parkinsonism and cognitive decline. Due to overlap of symptoms FXTAS can be mistaken for NPH leading to unwarranted therapeutic procedures Case: A 75 year old Arab gentleman with history of long-standing diabetes presented to internal medicine clinic with upper limb tremor followed by gait ataxia, urinary incontinence and progressive dementia. His CT brain showed dilated ventricles. He was referred to neurosurgery for possible ventriculoperitoneal shunt. Clinical examination revealed orthostatic hypotension, executive dysfunction with symmetric rigidity and bradykinesia, postural instability and bilateral upper limb ataxia and intention tremor. His MRI showed cerebral and cerebellar atrophy in addition to T2/FLAIR hyper intense lesions in the periventricular regions, the corpus callosum, bilateral middle cerebellar peduncles (MCPs) and in underlying cerebellar white matter lateral to the dentate nuclei which was highly suggestive of FXTAS. Genetic screening was positive for premutation of the FMR1 gene in the patient as well as his grandson with autistic spectrum disorder, which confirmed the diagnosis He was started on anticholinergic medications for dementia and required fludrocortisone for orthostatic hypotension. He continued to progress despite treatment. Genetic counseling was advised for the family Conclusion: FXTAS should be considered in the differential diagnosis of NPH. Thorough family history, identification of typical MRI brain findings and genetic screening helps to precisely diagnose the condition and avoiding unwarranted therapeutic procedures