Fragile X–associated tremor/ataxia syndrome results from a genetic mutation.
Tremors in the hands commonly develop first, followed by loss of coordination, slowed movements, decreased facial expression, and eventually dementia.
Genetic testing can confirm the diagnosis.
Primidone, propranolol, or medications used to treat Parkinson disease can often relieve the tremors.
(See also Overview of Movement Disorders Overview of Movement Disorders Every body movement, from raising a hand to smiling, involves a complex interaction between the central nervous system (brain and spinal cord), nerves, and muscles. Damage to or malfunction... read more .)
Fragile X–associated tremor/ataxia syndrome may affect as many as 1 of 3,000 men over 50.
Fragile X–associated tremor/ataxia syndrome results from an abnormality (called a premutation) in a gene on the X chromosome (one of the sex chromosomes). The premutation is less extensive than the full mutation that causes Fragile X syndrome Fragile X Syndrome Fragile X syndrome is a genetic abnormality on the X chromosome that leads to intellectual disability and behavior problems. Chromosomes are structures within cells that contain DNA and many... read more , which causes intellectual disability in children. Boys and men have an X and a Y chromosome, and women have two X chromosomes. Men inherit an X chromosome from their mother and a Y chromosome from their father. If the X chromosome they inherit from their mother contains the abnormal gene that causes Fragile X–associated tremor/ataxia syndrome, they have the disorder, which is classified as an X-linked disorder X-Linked Inheritance Genes are segments of deoxyribonucleic acid (DNA) that contain the code for a specific protein that functions in one or more types of cells in the body or code for functional RNA molecules.... read more . In X-linked disorders, the symptoms are usually more severe in boys and men. In girls and women, having two X chromosomes may help protect them.
People with the premutation are considered carriers (people who have an abnormal gene for a disorder but do not have the symptoms of the disorder). However, about 30% of men with the premutation and fewer than 5% of women with the premutation develop Fragile X–associated tremor/ataxia syndrome as adults. The risk of developing the disorder increases as people age.
Men with the premutation pass it to their daughters (but not to their sons). Most women with the premutation are unaffected and thus may unknowingly pass the gene on to their sons (grandsons of men with the premutation). Children of such a woman have a 50% chance of inheriting the premutation. When the premutation is passed from mother to child, it sometimes changes into a full mutation, causing Fragile X syndrome in the child.
Symptoms of FXTAS
Symptoms of Fragile X–associated tremor/ataxia syndrome usually develop during late adulthood.
The first symptom is often
Tremors in the hands, typically when people try to do a task
Other symptoms include tremors when at rest, loss of coordination (ataxia), slow movements, stiffness, and decreased facial expression (parkinsonian symptoms Symptoms Parkinsonism refers to symptoms of Parkinson disease (such as slow movements and tremors) that are caused by another condition. Parkinsonism is caused by brain disorders, brain injuries, or... read more ). As the disorder progresses, loss of coordination worsens.
People may have problems remembering recent events and solving problems. They may think more slowly. Mental function may progressively deteriorate. People may also have personality changes. They may become depressed, anxious, impatient, hostile, and moody.
Sensation in the feet may be lost. Internal organs may malfunction. Affected people may feel light-headed when they stand because blood pressure does not increase as it normally does (called orthostatic hypotension Dizziness or Light-Headedness When Standing Up In some people, particularly older people, blood pressure drops excessively when they sit or stand up (a condition called orthostatic or postural hypotension). Symptoms of faintness, light-headedness... read more ). Eventually, they may lose control of the bladder and bowel movements.
After symptoms appear, people may live from about 5 to 25 years.
In women with the premutation, symptoms are usually less severe, possibly because they have another X chromosome, which seems to protect against the effects of the X chromosome with the premutation. Women with the premutation are more likely to have early menopause and infertility problems than women without the premutation.
Diagnosis of FXTAS
A doctor's evaluation
Sometimes magnetic resonance imaging
Fragile X–associated tremor/ataxia syndrome is sometimes missed or mistaken for disorders that cause similar symptoms, such as Parkinson disease Parkinson Disease (PD) Parkinson disease is a slowly progressive degenerative disorder of specific areas of the brain. It is characterized by tremor when muscles are at rest (resting tremor), increased muscle tone... read more or Alzheimer disease Alzheimer Disease Alzheimer disease is a progressive loss of mental function, characterized by degeneration of brain tissue, including loss of nerve cells, the accumulation of an abnormal protein called beta-amyloid... read more . The tremors may be mistaken for essential tremor Essential tremor A tremor is an involuntary, rhythmic, shaking movement of part of the body, such as the hands, head, vocal cords, trunk, or legs. Tremors occur when muscles repeatedly contract and relax. (See... read more (a common tremor disorder that rarely causes any other symptoms).
If doctors suspect Fragile X–associated tremor/ataxia syndrome, they ask about symptoms in family members, particularly whether grandchildren have intellectual disability or daughters have had early menopause or infertility problems.
When doctors examine children with Fragile X syndrome, they should find out whether the grandfathers have any symptoms suggesting Fragile X–associated tremor/ataxia syndrome.
Magnetic resonance imaging Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (MRI) is a type of medical imaging that uses a strong magnetic field and very high frequency radio waves to produce highly detailed images. During an MRI, a computer... read more (MRI) may be done to check for characteristic abnormalities in the brain.
Genetic testing can confirm the diagnosis.
Daughters and grandsons of men with Fragile X–associated tremor/ataxia syndrome should have genetic counseling. Daughters can be tested for the premutation so that they can make decisions about whether or not to have children and whether or not to have prenatal testing Prenatal Testing for Genetic Disorders and Birth Defects Prenatal testing for genetic disorders and birth defects involves testing a pregnant woman or fetus before birth (prenatally) to determine whether the fetus has certain abnormalities, including... read more if pregnancy occurs.
Treatment of FXTAS
Medications to control the tremors
Tremors can often be relieved by primidone (an antiseizure medication), propranolol (a beta-blocker), or many of the medications used to control tremors due to Parkinson disease Drugs Used to Treat Parkinson Disease .
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
Genetics Home Reference: Fragile X syndrome: This web site describes fragile X syndrome and discusses what causes it and how it is inherited, as well as provides links to its diagnosis and treatment.
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