Fragile X syndrome is a genetic condition caused by a mutation of the fragile X mental retardation 1 (FMR1) gene on the X chromosome.
Fragile X syndrome in males is usually more severe than in females and males are never asymptomatic. This is because males have only one X chromosome (unlike females that have 2 “X” chromosomes) and therefore any defect on the X chromosome is likely to be displayed. Females tend to have fewer and milder abnormalities than males. This is because they inherit two X chromosomes, one of which is inactivated randomly in each cell.
Common symptoms include:
- Behavior – Characterized by autism spectrum behaviors such as attention deficit disorder, hyperactivity, expressive delay, tactile defensiveness, repetition of words and phrases, echolalia (parrot like repetition of a word or phrase that has just been spoken by another person), social anxiety and avoidance of eye contact.
- Cognitive – Males with full mutation have moderate to severe mental impairment. Difficulty comprehending abstract ideas, organization of information, planning ahead and with problem-solving skills.
- Health problems – Seizures occur in 10 to 20% of males with Fragile X syndrome. Most are simple or complex partial seizures. The seizures often spontaneously remit during childhood and occur less frequently in women.
- Appearance/physical characteristics – Some boys have a soft, broad forehead compared to children of their own age. Physical characteristics become more obvious during the teenage years. For example, the characteristic elongated face becomes more obvious during teenage years. During puberty, boys often have macroorchidism, flat feet, hyper flexible joints, mitral valve prolapse. Girls that have fragile X syndrome often experience premature ovarian failure (early menopause). Both boys and girls may develop a tremor which can appear like Parkinson’s disease.
Entire Body System
- Developmental Disorder
Background: Retrospective parental reports have often been used to identify the early characteristics of children later diagnosed with a developmental disorder. [ncbi.nlm.nih.gov]
The mother proved to be an asymptomatic carrier of all three non-contiguous mutation events, involving the STS gene, the DMD gene and a FMR1 expansion. [ncbi.nlm.nih.gov]
In asymptomatic individuals, the FMR1 allele has between 6 and 53 CGG repeats. In people with the disorder, the FMR1 allele has over 230 repeats. [web.archive.org]
Screening is important as it aids family planning by identifying asymptomatic premutation/full mutation carriers, allowing couples to make more informed reproductive decisions. [dmb-diagnostics.de]
Fragile X syndrome in males is usually more severe than in females and males are never asymptomatic. [symptoma.com]
- Family History of Intellectual Disability
It is important for physicians to be aware of the possibility that females presenting with partial seizures of unknown cause may be fragile-X carriers, and enquiry for a family history of intellectual disability should be pursued. [ncbi.nlm.nih.gov]
Family History Ask about a family history of intellectual disability (with or without a specific diagnosis), FXS, and/or autistic spectrum disorder. [medicalhomeportal.org]
- Mitral Valve Prolapse
Mitral valve prolapse — A heart defect in which one of the valves of the heart (which normally controls blood flow) becomes floppy. Mitral valve prolapse may be detected as a heart murmur but there are usually no symptoms. [medical-dictionary.thefreedictionary.com]
Heart defects (e.g., mitral valve prolapse), dilatation of the aortic root, and seizures have been described. [accessanesthesiology.mhmedical.com]
The joints may be hyperextensible, and heart disease (mitral valve prolapse) may occur. Cognitive abnormalities may include mild to moderate intellectual disability. [merckmanuals.com]
Hagerman RJ & Synhorst DP (1984) Mitral valve prolapse and aortic dilatation in the fragile X syndrome. Am J Med Genet 17(1): 123-131. Abstract on Pubmed. 18. [forgottendiseases.org]
The joints may be hyperextensible, and heart disease ( mitral valve prolapse ) may occur. Cognitive abnormalities may include mild to moderate intellectual disability. [msdmanuals.com]
Affected people may feel light-headed when they stand because blood pressure does not increase as it normally does (called orthostatic hypotension). Eventually, they may lose control of the bladder and bowel movements. [msdmanuals.com]
Clinical features of FXTAS include incontinence, impotence, cerebellar ataxia, peripheral neuropathy, autonomic dysfunction/orthostatic hypotension, severe intention tremor, and other signs of neurodegeneration, such as brain atrophy, memory loss and [emedicine.com]
Adults, however, may experience additional health challenges including CF-related diabetes and osteoporosis. CF also can cause reproductive problems - more than 95 percent of men with CF are sterile. [who.int]
The state of early estrogen deficiency leads to additional clinical consequences such as an increased risk of low bone density, earlier onset osteoporosis and bone fractures [ 14 ], impaired endothelial function [ 15 ], earlier onset of coronary heart [doi.org]
Features of attention-deficit/hyperactivity disorder, including hyperactivity, inattentiveness, distractibility, restlessness, and impulsivity, are present in 80% of patients with fragile X syndrome. [pediatrics.aappublications.org]
Because many people with Fragile X also have attention disorders, hyperactivity, anxiety, and language-processing problems, a person with Fragile X may have more capabilities than his or her IQ (intelligence quotient) score suggests. Physical. [web.archive.org]
These may include features of: Attention deficit disorder Hyperactivity Impulsivity Anxiety Mood swings There are typical facial features and physical attributes of FXS. [news-medical.net]
Adults with fragile X [ edit ] Hyperactivity tends to improve in adolescents and adults with fragile X Anxiety, (particularly social anxiety) is present and more common in individuals who are not impulsive or hyperactive Anxiety or uncertainty often leads [en.wikibooks.org]
- Personality Change
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. [msdmanuals.com]
Diagnosis for fragile X syndrome is based on molecular genetic analysis that measures the length of the CGG repeats in the FMR-1 region. This test can be performed from a blood sample and/or (in a fetus), through amniotic fluid testing.
The goal of treatment is to minimize the symptoms resulting from fragile X syndrome. Management of children and adolescents with fragile X syndrome is individualized according the degree and type of child’s cognitive and behavioral symptoms, strengths and weaknesses.
Genetic counseling should be offered to families of individuals with fragile X syndrome, since this may be an inherited disorder.
Children and adolescents with fragile X syndrome have special educational and behavioral needs and should be referred to counselors and speech therapists for help with coping and minimizing the associated problems.
Life span is generally unaffected by the disorder.
A mutation of the fragile X mental retardation 1 (FMR1) gene on the X chromosome causes the clinical features of the fragile X syndrome.
Both genders can be affected; it occurs more commonly in males (1 in 3600 males compared to 1 in 4000-6000 females).
Platelets are indeed an attractive model for unraveling pathophysiological mechanisms involved in NDD as well as to search for diagnostic and therapeutic biomarkers. [ncbi.nlm.nih.gov]
There is no guideline for the prevention of fragile X syndrome.
Fragile X syndrome is a genetic condition that a person is born with. It is a result of a defect of a part of the “X” chromosome. Fragile X syndrome causes learning and behavior problems, as well as abnormal body features. It occurs more commonly in boys than girls. The cause is unknown; it may be inherited or a result of unexpected damage to the X chromosome.
What are the symptoms?
Symptoms that commonly occur in persons with Fragile X include:
- Larger than normal head
- Crossed eyes
- Large ears and “sunken in” eyes
- Flat feet
- Testicles that are larger than normal in male teenagers and adults.
- Learning and behavior problems such as:
- Difficulty performing problem solving and tasks that involve organization
- Difficulty with language and speaking
- Trouble sitting still, paying attention
- Feel anxious, worried or sad often
- Medical problems, such as:
- Tremor (shaking of the hands)
How is it diagnosed?
Diagnosis is made through a family history screening during which your doctor will ask if any member of your family has had symptoms seen in patients with fragile X syndrome. Then a blood test will be performed that will determine if a person has problems with their X chromosome.
What is the treatment?
Currently there is no cure for fragile X syndrome. Treatment centers around controlling a person’s symptoms. For example, a children’s teacher can help develop a special learning plan, behavior counselors and speech therapists can work with a child to help improve language and behavior problems, certain medications may be prescribed to help a child pay attention.
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