Fragile X–Associated Tremor/Ataxia Syndrome (FXTAS)

FXTAS symptoms become noticeable in late adulthood. The more CGG repeats, the more severe the symptoms and the earlier the onset.

Tremor Tremor Tremors are involuntary, rhythmic, oscillatory movements of reciprocal, antagonistic muscle groups, typically involving the hands, head, face, vocal cords, trunk, or legs. Diagnosis is clinical... read more , often misdiagnosed as essential tremor, is a common early symptom of FXTAS. Tremors are usually intention tremors. Patients develop ataxia (which progressively worsens), then parkinsonism Secondary and Atypical Parkinsonism Secondary parkinsonism refers to a group of disorders that have features similar to those of Parkinson disease but have a different etiology. Atypical parkinsonism refers to a group of neurodegenerative... read more (including a resting tremor), and eventually dementia.

Patients with other X chromosome disorders (eg, Klinefelter syndrome Klinefelter Syndrome (47,XXY) Klinefelter syndrome is the presence of two or more X chromosomes plus one Y, resulting in a phenotypic male. Diagnosis is based on clinical findings and is confirmed by cytogenetic analysis... read more [XXY karyotype]) may have tremor that mimics essential tremor.

Dementia begins with loss of short-term memory, slowed thought, and difficulty problem solving. Depression, anxiety, impatience, hostility, and mood lability may develop.

Peripheral neuropathy Overview of Peripheral Nervous System Disorders The peripheral nervous system refers to parts of the nervous system outside the brain and spinal cord. It includes the cranial nerves and spinal nerves from their origin to their end. The anterior... read more is often present, causing loss of sensation and reflexes in the feet. Dysautonomia (eg, orthostatic hypotension Orthostatic Hypotension Orthostatic (postural) hypotension is an excessive fall in blood pressure (BP) when an upright position is assumed. The consensus definition is a drop of > 20 mm Hg systolic, > 10 mm Hg... read more ) may occur. In later stages, bladder and bowel control may be lost.

Life expectancy after motor symptoms develop ranges from about 5 to 25 years.

In women with the premutation, symptoms are usually less severe, possibly because the presence of another X chromosome is protective. These women have an increased risk of early menopause, infertility, and ovarian dysfunction.

If FXTAS is suspected, patients should be asked whether any of their grandchildren have intellectual disability and whether their daughters have had early menopause or infertility.

Also, if a patient has Fragile X syndrome, clinicians should determine whether the patient's grandparents have symptoms suggesting FXTAS; if so, genetic counseling is recommended for the grandparent's children and grandchildren.

MRI is done; it may identify the characteristic increased signal in the middle cerebellar peduncles.

Diagnosis of FXTAS is confirmed by genetic testing.

The resting tremor in FXTAS can often be relieved with primidone, propranolol, topiramate, gabapentin, pregabalin, benzodiazepines, and/or antiparkinsonian drugs Treatment Parkinson disease is a slowly progressive, degenerative disorder characterized by resting tremor, stiffness (rigidity), slow and decreased movement (bradykinesia), and eventually gait and/or... read more ; doses have not yet been standardized (1 Treatment reference Fragile X–associated tremor/ataxia syndrome is a genetic disorder affecting mostly men and causing tremor, ataxia, and dementia. Tremor is a common early symptom that is followed by ataxia,... read more , 2 Treatment reference Fragile X–associated tremor/ataxia syndrome is a genetic disorder affecting mostly men and causing tremor, ataxia, and dementia. Tremor is a common early symptom that is followed by ataxia,... read more ).