A genetic disorder, Fragile X syndrome (FXS) affects the development of the brain and body. It is the leading cause of intellectual disability and autism spectrum disorder. There are many physical, mental, and behavioral problems that can result from FXS, ranging from mild to severe. It affects both sexes, but males are generally more severely affected.
In FXS, the FMR1 gene, which is located on the X chromosome, is mutated. The X chromosome determines a person's biological sex. Females have two X chromosomes, while males have one X chromosome and one Y chromosome.
Normally, the FMR1 gene produces a protein called FMRP, which is crucial for brain development and function. Mutations in the FMR1 gene prevent FMRP from being produced or render it defective, which leads to impaired nerve cell communication and abnormal brain development.
An FMR1 mutation is referred to as a CGG repeat expansion, which means that a DNA segment containing three letters (CGG) is repeated many times throughout the gene. The normal number of CGG repeats in the FMR1 gene is between 5 and 44. People with 45 to 54 CGG repeats are called intermediate carriers. They do not have FXS, but may have some health problems or pass the mutation on to their children. Those with 55 to 200 CGG repeats are called premutation carriers. They do not have FXS, but may have health problems or pass on the mutation to their children. Those with more than 200 CGG repeats are known as full mutation carriers. They may have a variety of symptoms and complications related to FXS.
People with FXS will have FXS regardless of their sex if they possess a full mutation in their X chromosomes. Due to the fact that males have only one X chromosome and no other copies of the FMR1 gene, they are more likely to suffer severe symptoms. In females with two X chromosomes, there may be a normal copy of the FMR1 gene on the other X chromosome, which can partially compensate for the mutated gene.
It has a 50% chance of being passed to each of a person's children if they have the full mutation in the FMR1 gene, regardless of their gender. Premutations in the FMR1 gene have a variable chance of passing on to their children, depending on the number of CGG repeats and their gender. It is more likely for a female premutation carrier to pass on the premutation or the full mutation to her children than a male premutation carrier. It is only possible for a male premutation carrier to pass on the premutation to his daughters, not to his sons.
Symptoms of FXS vary widely among individuals, depending on the severity of the mutation, the sex of the individual, and other genetic and environmental factors. Some people with FXS may only have mild symptoms, while others may have severe impairments. These symptoms include:
FXS is characterized by features such as a long and narrow face, large ears, a prominent forehead and chin, flat feet, loose joints, and low muscle tone. Males with FXS may also have enlarged testicles (macroorchidism) after puberty.
Developmental delays, such as taking longer than normal to crawl, walk, talk, or learn new skills. Some people with FXS may never achieve these milestones.
FXS can cause developmental delays, such as taking longer to crawl, walk, talk, or learn new skills.g individuals, from mild to profound. Males with FXS tend to have lower IQ scores than females with FXS.
There are different degrees of intellectual disability among individuals, rangingo have features of autism spectrum disorder, such as impaired social interaction, communication, and repetitive behaviors.
Sensory issues, such as being sensitive to certain sounds, lights, textures, or smells. Some people with FXS may also have sensory-seeking behaviors, such as craving stimulation or touch.
Medical problems, such as seizures, ear infections, sinusitis, eye problems, heart defects, and gastrointestinal issues. Some people with FXS may also have sleep problems, such as difficulty falling asleep or staying asleep.
The diagnosis of FXS is based on the following:
During the clinical evaluation, the person is examined, provided with a medical history, and assessed for developmental, cognitive, and behavioral characteristics. In addition to looking for signs of FXS in the person, the doctor may also look for it in relatives with intellectual disabilities, autism, or other health problems.
Genetic testing, which involves a blood test that can detect the mutation in the FMR1 gene. This test determines whether the patient has a normal, intermediate, premutation, or full mutation based on the number of CGG repeats in the gene. Genetic testing can also identify a person's sex and the X chromosome that carries the mutation. It can be done before or after birth, depending on its purpose and availability.
To rule out other conditions that may cause similar symptoms, such as chromosome abnormalities, metabolic disorders, or brain injuries, other tests may be performed. FXS may also be accompanied by other medical tests, such as hearing tests, vision tests, electroencephalograms (EEGs), echocardiograms, or gastrointestinal tests, ordered by the doctor.
Despite the lack of a cure for FXS, there are many treatments that can improve the quality of life of people with FXS and their families. Therapies for FXS include:
Medications can help manage some of the symptoms and complications of FXS, like seizures, anxiety, depression, hyperactivity, aggression, or sleep problems. Several types of drugs may be prescribed by the doctor, including anticonvulsants, antidepressants, antianxiety drugs, stimulants, and antipsychotics. It is important to use the medication under the supervision of your doctor, as some medications may have side effects or interact with others.
A variety of professionals may be involved in the therapy, including speech therapists, occupational therapists, physical therapists, psychologists, and special educators, which can help people with FXS develop, learn, communicate, and behave. As part of the therapy, you may receive speech and language therapy, sensory integration therapy, behavioral therapy, cognitive-behavioral therapy, social skills training, or applied behavior analysis. The therapy may be provided in different settings, such as home, school, or clinic.
People with FXS may benefit from education, which can provide a supportive learning environment. Different types of services can be provided, including early intervention, special education, individualized education plans (IEPs), or transition plans. There may also be accommodations included in the education, such as modifying the curriculum, using assistive technology, or providing peer support. The education should be tailored to each individual's strengths and interests, as well as their challenges and needs.
For people with FXS and their families, support can be provided emotionally, socially, and practically. In addition to family members, friends, caregivers, counselors, support groups, and organizations, support may also include different activities, such as recreation, hobbies, sports, or the arts. Individuals and their families should be provided with support that aims to enhance their well-being, self-esteem, and independence.
There is no way to prevent FXS, as it is a genetic disorder that is inherited from parents. However, there are some steps that can help reduce the risk or impact of FXS, such as:
Those who plan to have children and carry the mutation or have a family history of FXS can benefit from genetic counseling, which provides information and guidance. According to a genetic counselor, the child's chances of passing on the mutation, the child's possible outcomes, and the treatment options available. As part of the decision-making process, genetic counselors can also help resolve emotional and ethical issues.
In pregnancy, there are various methods of prenatal testing, including chorionic villus sampling (CVS) and amniocentesis, which can be used to detect a mutation in the FMR1 gene in the fetus. The prenatal testing can help confirm or rule out the diagnosis of FXS in the fetus, helping parents prepare for the birth and care of the child. The prenatal testing can also help the parents decide whether to continue or terminate the pregnancy, depending on their personal values and preferences.
During newborn screening, a blood test can be used to identify a mutation in the FMR1 gene in a baby after birth. This test is usually done in conjunction with other routine baby tests. As a result of newborn screening, parents can get access to appropriate services and interventions for their child and diagnose FXS early. Furthermore, the newborn screening can help parents better understand what FXS means to them and their future children.
