Overview

Sociable and loving personality
Enjoyment of humor and fun
High activity level
Short attention span
Perseveration (repetition of phrases and activities)
Impulsivity
Stereotypic movements such as hand flapping, toe walking, spinning objects
Hand biting
Tantrums or unusually strong reactions to situations
Sensory seeking behaviors such as overstuffing mouth, mouthing or chewing objects
Fleeting eye contact
Poor adaptation to changes in routine
Resistance to being touched or held
Sensitivity to touch, smells, and noises
Shyness or anxiety around unfamiliar people

Normal stature
Broad forehead, large head
Large, prominent ears
Frequent ear infections
Flexible joints
Low muscle tone
Soft, fleshy skin
Flat feet
Strabismus (crossed eyes) or refractive errors
Chest indentation
Mitral valve prolapse (benign heart condition)
Seizures (in 10 percent)

Delays in meeting milestones (sitting, walking, talking, toilet training)
Speech and language delays
Wide spectrum of cognitive functioning ranging from learning disabilities to mild, moderate, or severe mental retardation
Sensory integration and processing problems

Gaze aversion
Mood instability
Anxiety

Elongated face
High arched palate
Hand calluses
Enlarged testicles

Creative and warm personality
Socially shy and anxious
Sensitivity to touch, smells, and noises
Stereotypic movements such as hand flapping, toe walking, or spinning objects
Fleeting or infrequent eye contact
Tangential speech

Normal stature
Mildly prominent ears
Flexible joints
Low muscle tone
Flat feet
Strabismus (crossed eyes) or refractive errors

Delays in meeting milestones (sitting, walking, talking, toilet training)
Speech and language delays
Wide spectrum of cognitive functioning ranging from normal development to learning disabilities to mild, moderate, or severe mental retardation
Executive function (organizational, sequential and planning skills) deficits
Sensory integration and processing problems

Fragile X Syndrome is a single gene disorder located on the X chromosome. Understanding the basics of fragile X syndrome requires an understanding of how genes themselves are constructed and what they do.
Genes are made up of DNA, which provides the blueprint for life. This blueprint is a code containing four letters (C, G, A, T), abbreviations for four different nucleotides (cytosine, guanine, adenine, and thymine). Nucleotides are the essential building blocks that make DNA. The letters and the sequences in which they are arranged construct the messages that lead the body to produce key proteins.

Fragile X syndrome results from a mutation (a change in the typical DNA sequence) known as trinucleotide repeat expansion. This means that a series of three particular nucleotides (CGG) in the DNA is greatly expanded beyond its normal size, disrupting the normal messages that need to be sent. This fact was discovered in 1991 by several teams of researchers studying the X chromosome.

In the FMR-1 gene located on the X chromosome, most individuals have CGG repeat that occurs between 5 and 50 times, the average being around 30. These individuals are normal with respect to fragile X syndrome, and usually carry no risk of transmitting it, although the 40—60 repeat range is sometimes considered a "gray zone" which may or may not be unstable (have a risk of expanding). Some individuals have CGG sequences that are repeated in the range of about 50 to 200. These individuals are generally referred to as premutation carriers. This means that they carry the syndrome and can transmit it to their children. Premutation carriers, however, are not usually affected by fragile X syndrome. When the number of CGG repeats expands beyond 200, the individual usually has the full mutation. This means that they have fragile X syndrome and will experience the impairments and delays associated with the syndrome.

Detecting Fragile X Syndrome

Fragile X syndrome is detected through a DNA analysis that almost always requires drawing blood. The technique for identifying fragile X syndrome is a specialized process and not all genetic labs have this capability. For those that do have this capability, the procedure is virtually 100 percent reliable. Fragile X can be detected prenatally or in newborns through DNA testing. Also, the carrier status of parents can be accurately determined. However, these tests are not routinely done and must be specifically requested. It is impossible to determine how severely affected the child might be based on this procedure.

Inheriting Fragile X Syndrome

Fragile X syndrome is carried on the X chromosome. Since both males (XY) and females (XX) each have at least one X chromosome, both can be carriers or have the syndrome. If a father is a carrier, he can only pass the gene defect to his daughters, since he transmits a Y chromosome to his sons. All of his daughters will inherit the gene, and as far as is known, transmission from father to daughter only occurs in the premutation state. In other words, if a daughter inherits the gene from her father, she will have the premutation, not the full mutations. Interestingly, this happens even if the father has the full mutation, as the sperm cells of males with the full mutation have been shown to be in the premutation phase.

If a mother is the carrier, she can pass the gene defect to either sons or daughters, since she contributes an X chromosome to each. Children of carrier mothers have a 50 percent chance of inheriting the gene, since the mother has two Xs to give and only one is affected. It is through mothers that the gene can expand from the premutation to the full mutation. So, a carrier mother can have normal children, children with the premutation, or children with the full mutation.

The chances of expansion into the full mutation increase with successive generations. Thus the gene could be passed down in the premutation phase for several generations without anyone suspecting that the family has a genetic disorder that ultimately will lead to mental retardation or other developmental disabilities.

Promoting Early Identification


Most cases of Down syndrome are identified at birth on the basis of physical features. However, in fragile X syndrome delays and physical features are not obvious at birth. In our sample of 75 parents of young boys with fragile X syndrome, typically someone first becomes concerned about the child around 8-10 months of age. Typical concerns voiced are inability to cuddle, lack of regular routines, fussiness or delayed attainment of developmental milestones (walking, talking). Sometimes these signs are subtle, and it may take a long time for a physician or other professional to acknowledge that a problem exists. It is not until about 22-24 months, however that the typical child is diagnosed as developmentally delayed. It is still another year before the average child in our sample was diagnosed with FXS (35 months). As a result, many cases of fragile X syndrome remain undiagnosed or are diagnosed later than most parents would prefer. Parents report significant frustration with the barriers they face in trying to find out what is wrong with their child. Although we are now beginning to study infant and toddler development in order to improve early identification, reliance on behavioral and physical features alone will make early identification very difficult. Considerable discussion is now going on regarding the costs and benefits of various genetic screening options.


Supporting Extended Families


Often fragile X syndrome is identified in families where there was no prior knowledge of its existence. Because it is an inherited disorder, other family members inevitably become involved and may be identified as carriers or as having the disorder. The process of informing other family members and helping extended family members cope with this unexpected information is challenging and one for which outside support can be especially helpful.


Determining Medical Treatments


There is no cure for fragile X syndrome. Many researchers are studying gene therapy in hopes of ultimately identifying ways to correct genetic disorders. However, this process has yet to be successful with any disease, and since brain disorders pose unique challenges, a cure is unlikely in the near future. Medical interventions are thus primarily limited to medications. A number of medications have been identified as being helpful in addressing problems related to anxiety, attention, and activity. However, there is not a standard prescription regimen and usually several drugs must be tried independently or in combination with each other before an effective treatment is identified.


Determining Educational & Therapeutic Treatments


Most persons with fragile X syndrome need special education and therapeutic services. Unfortunately, little research has systematically examined the effectiveness of various treatments or interventions. General suggestions include designing a structured, predictable environment, eliminating distractions, allowing for periods of rest and escape from demands, and clear communication of expectations and feedback. Speech and language therapy as well as occupational therapy are recommended for most affected individuals.


Differentiating FXS & Autism


Children with fragile X syndrome may display autistic-like behaviors such as hand-flapping or social avoidance, and many are initially referred for an autism evaluation. Research shows that while fragile X syndrome is not a major cause of autism, about 15-25% of persons with fragile X syndrome may meet diagnostic criteria for autism at some point in their lives. However, the basis for autistic-like behavior may be different for the two populations and more research is needed on the implications for treatment.