10 Fragile X Syndrome Symptoms
Fragile X syndrome is a genetic condition inherited in an X-linked dominant pattern. It is usually due to the expansion of the CGG triplet repeat (trinucleotide repeat) within the Fragile X Mental Retardation 1 (FMR1) gene present on the X chromosome.
Diagnosis can be achieved through genetic testing. Testing for premutation carriers helps provide genetic counseling. Although there is no cure, early intervention is important as it increases the chances for patients to develop more skills. Interventions include behavioral therapy, special education, physical therapy, and speech therapy.
Medications may be necessary to manage mood problems, seizures, aggressive behavior, and more. Fragile X syndrome has been estimated to occur in 1.4 in 10,000 males and 0.9 in 10,000 females.
Symptom #1: Intellectual Disability
Those with fragile X syndrome can present with severe intellectual disabilities. Male patients with fragile X syndrome have an average intelligence quotient (IQ) of 40 if they have complete silencing of the FMR1 gene. Females tend to be less affected and usually present with an IQ of borderline learning difficulties or normal. These individuals face difficulties in executive function, short-term memory, working memory, visual spatial relationships, visual memory, and mathematics.
While the data on intellectual development among patients with fragile X syndrome is limited, there is some evidence that observed that their standardized IQ decreases with time due to slowed intellectual development. If autism is also present, there is greater deficit in IQ and language compared to those with only fragile X syndrome.
Symptom #2: Different Facial Characteristics
Individuals with fragile X syndrome usually exhibit a long narrow face, high arched palate, and prominent ears. Other reported features include long palpebral fissures, jaw prominence, puffiness surrounding the eyes, epicanthal folds, decreased inner canthal separation, broad nose, strabismus, and hypotonia. The different facial characteristics tend to occur more commonly in male patients with fragile X syndrome compared to their female counterparts.
It should be noted that it is not reliable to propose the diagnosis of fragile X syndrome based on looks alone. The different features may not be noticeable until after puberty.
Symptom #3: ADHD
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental mental disorder where those affected have issues with excessive activity, issues with paying attention, and difficulty controlling their behavior. Symptoms are usually present before 12 years of age and can result in problems in school. In male patients with fragile X syndrome, it has been observed that some have behavioral features of those with ADHD such as attention deficits and aggressive tendencies.
ADHD has been estimated to affect most boys and 30 percent of girls with fragile X syndrome. They can be treated using stimulants. However, the use of stimulants can result in irritability, anxiety, and mood lability.
Symptom #4: Macroorchidism
Macroorchidism is a condition where the male patient has abnormally large testes. It is a common inherited condition associated with fragile X syndrome. Microorchidism is on the other side of the spectrum where there are abnormally small testes.
Besides fragile X syndrome, other potential causes of macroorchidism include lymphomas, aromatase deficiency, primary hypothyroidism, follicle stimulating hormone secreting pituitary macroadenomas, adrenal remnants in congenital adrenal hyperplasia, and local tumors.
Symptom #5: Hypersensitivity and Repetitive Behavior
Children who have fragile X syndrome are usually hyperactive and have short attention spans. They also seem to be hypersensitive to olfactory, visual, tactile, and auditory stimuli. This causes difficulty adapting to large crowds due to loud noises resulting in hyperarousal (fight or flight response) and tantrums. They can also be picky about the texture of materials such as clothing as they find certain textures to be irritating. Transition can be difficult.
Management includes behavioral therapy. These individuals also tend to have repetitive behavior, where they repeat the same phrase and continually talk about the same subject. They also tend to self-talk, have cluttered speech, and repeat activities.
Symptom #6: Working Memory
From the age of 40 upward, male patients with fragile X syndrome start to gradually have more issues with performing tasks that require their working memory. Working memory involves the transient information storage while processing other information. Verbal working memory or phonological memory worsens with age.
Some researchers believe that the working memory deficits may be due to a dysfunction that occurs in the front part of their brain.
Symptom #7: Visual Issues
Visual issues are also seen among individuals with fragile X syndrome. Some examples include strabismus and amblyopia. Strabismus occurs when the eyes are not aligned with each other when one is looking at an object. It can result in loss of depth or amblyopia. Amblyopia or lazy eye results in decreased vision and is the commonest cause of vision impairment in one eye among younger adults and children.
Patching or surgery are usually required for the treatment of strabismus if there is an early diagnosis. Refractive errors are also common among patients with fragile X syndrome.
Symptom #8: Autism or Autism-Like Behavior
Patients with fragile X syndrome also experience autistic-like behavior. This includes social avoidance, poor eye contact, hand flapping, and hand biting. This can be seen in 16 to 30 percent of fragile X syndrome patients.
Autism is a condition where there are issues with communication, social interaction, and repetitive behavior. Signs and symptoms of autism are usually noticed during the first 2 to 3 years of a child’s life. Among patients with fragile X syndrome, approximately 20 percent of females and 30 percent of males are diagnosed with autism. An additional 30 percent of fragile X syndrome patients are diagnosed with autism spectrum disorder.
Symptom #9: Social Anxiety
Patients with fragile X syndrome have been observed to experience social anxiety, which can be characterized by gaze aversion, poor eye contact, difficulty forming relationships with their peers, and taking a long time to start social interaction. It is one of the commonest symptoms in those with fragile X syndrome.
In a study, up to 75 percent of males displayed excessive shyness with 50 percent experiencing panic attacks. These individuals also displayed greater sympathy than others with intellectual disability. However, patients with fragile X syndrome can display withdrawal and anxiety when they are in unfamiliar environments and people.
Symptom #10: Seizures
A seizure occurs when there is abnormally excessive activity in the brain. It can result in involuntary uncontrolled shaking involving the whole body with loss of consciousness (tonic clonic) or shaking that only involves part of the body (focal). Some patients have a momentary loss of awareness (absence).
Most seizures lasts less than 2 minutes. Patients with fragile X syndrome have been reported to have a higher risk of seizures ranging from 10 to 40 percent. Some estimate 20 percent of males and 5 percent of females with fragile X syndrome experience a seizure disorder with half requiring medication. The seizures are usually partial and usually respond well to medication.
