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
- 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
The joints may be hyperextensible, and heart disease ( mitral valve prolapse ) may occur. Cognitive abnormalities may include mild to moderate intellectual disability. [msdmanuals.com]
mitral valve prolapse), dilatation of the aortic root, and seizures have been described. [accessanesthesiology.mhmedical.com]
valve prolapse Evaluation Diagnosis is based primarily on clinical observation and family history Head circumference may be larger than average at birth Genetic studies may confirm Fragile X syndrome number of gene repeats can provide insight into anticipating [step2.medbullets.com]
There may be features due to changes in connective tissue including prominent ears, hyperextensible finger joints, mitral valve prolapse, soft skin and flat feet. [patient.info]
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]
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. [nichd.nih.gov]
The FMR1 mutations can cause a variety of disabilities, including cognitive deficits, attention-deficit/hyperactivity disorder, autism, and other socioemotional problems, in individuals with the full mutation form (fragile X syndrome) and distinct difficulties [ncbi.nlm.nih.gov]
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.
- Turner G, Webb T, Wake S, Robinson H. Prevalence of fragile X syndrome. Am J Med Genet 1996; 64:196.
- Verkerk AJ, Pieretti M, Sutcliffe JS, Fu YH, Kuhl DP, Pizzuti A, Reiner O, Richards S, Victoria MF, Zhang FP. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell. 1991;65(5):905.
- Fisch GS, Simensen R, Tarleton J, Chalifoux M, Holden JJ, Carpenter N, Howard-Peebles PN, Maddalena A. Longitudinal study of cognitive abilities and adaptive behavior levels in fragile X males: a prospective multicenter analysis. Am J Med Genet. 1996;64(2):356.
- Garber KB, Visootsak J, Warren ST. Fragile X syndrome. Eur J Hum Genet. 2008;16(6):666.
- Philofsky A, Hepburn SL, Hayes A, Hagerman R, Rogers SJ. Linguistic and cognitive functioning and autism symptoms in young children with fragile X syndrome. Am J Ment Retard. 2004;109(3):208.
- Musumeci SA, Hagerman RJ, Ferri R, Bosco P, Dalla Bernardina B, Tassinari CA, De Sarro GB, Elia M Epilepsy and EEG findings in males with fragile X syndrome. Epilepsia. 1999;40(8):1092.
- Bennetto L, Pennington BF, Porter D, Taylor AK, Hagerman RJ. Profile of cognitive functioning in women with the fragile X mutation. Neuropsychology. 2001;15(2):290.
- Hagerman RJ, Jackson C, Amiri K, Silverman AC, O'Connor R, Sobesky W. Girls with fragile X syndrome: physical and neurocognitive status and outcome. Pediatrics. 1992;89(3):395.
- Sherman S, Pletcher BA, Driscoll DA. Fragile X syndrome: diagnostic and carrier testing. Genet Med. 2005;7(8):584.
- Whissell PD, Lecker I, Wang DS, Yu J, Orser BA. Altered expression of δGABAA receptors in health and disease. Neuropharmacology. 2014 Aug 13.