Fragile X Syndrome (FXS) is an inherited genetic disorder that results in a range of characteristics which include autistic-like features, such as gaze avoidance, hand-flapping, difficulty with transitions, and impaired social and communication skills. It is the most commonly known inherited cause of intellectual disability, affecting 1 in 4,000 males and 1 in 8,000 females (Dykens, Hodapp, & Finucane, 2000). Organizations such as the National Fragile X Foundation and FRAXA are working to raise awareness about FXS; however, families continue to consistently hear “Fragile what?” when advising physicians, clinicians, teachers, friends, and neighbors of their child’s condition.
The syndrome is called “Fragile X” because the genetic mutation, which is caused by excessive repeats of the tri-nucleotide cytosine-guanine-guanine at a specific marker on the X chromosome, appears to be fragile or broken in that spot when viewed under a microscope. The typical number of CGG repeats is 30 – 50; when it exceeds 200, the mutation causes a protein, named the FMR-1 protein, not to be produced, which results in a spectrum of symptoms that impact cognition, behavior, and physiology. FXS affects males more than females because females typically have an unaffected X chromosome, so they produce some FMR-1 protein. It is common for affected females to have difficulty with math and social anxiety; some can have more extensive and severe symptoms comparable to males. Most males with FXS have mild or moderate cognitive impairment, hyperactivity and attention deficits, and a number of difficulties with language, including articulation, pragmatics, and tangential speech. Studies indicate from 15 – 25% of individuals with FXS meet the diagnostic criteria for autism; 2 – 4 % of individuals with autism are diagnosed with FXS (Demark, Feldman, & Holden, 2003).
Knowing how FXS impacts a person promotes understanding and can provide others with tools to bring out the best in affected individuals. People with FXS have nervous systems which are highly prone to hyperarousal, identified by researchers as a core deficit influencing many other symptoms of the disorder (Belser & Sudhalter, 1995). Hyperarousal can be instantly triggered by a wide range of environmental stimuli and circumstances. These include a host of sensory sensitivities, such as light, sound, and touch. Conventional social interactions, such as direct eye contact and open-ended questioning, can also be lead to reactive episodes. The high anxiety levels that result from these triggers further impair the person’s ability to speak and process information. When calm, individuals with FXS are often extremely social, known for a great sense of humor and a desire to be helpful. When their nervous systems are overwhelmed, however, they can lose control, reacting to ordinary demands with tantrums, self-injurious or aggressive behavior.
Individuals with FXS are known to demonstrate greater independence and ability in performing activities of daily living than is typically expected of individuals who test at comparable IQ scores. Testing conditions, which typically require eye contact, sitting still and answering direct questions, exacerbate hyperarousal in examinees with FXS; for this reason, experts are concerned that their cognitive capacity is under-estimated (Braden, 2000). I have heard many families report with amazement and pride that their child will at times contribute a sophisticated bit of information to a conversation they thought was way over their head. At other times, to their frustration, they are met with confusion or no response at all when attempting engagement in a very basic dialogue.
Empirical research has established a profile for individuals with FXS which includes a spontaneous vs. sequential learning style (Kemper, Hagerman, & Altshul-Stark, 1988). Individuals with FXS are “big picture” processors – they notice everything at once, rather than first one thing followed by another. Consequently, students with FXS struggle greatly with phonetics, which requires sounding out letters in a sequence. They are much more successful at learning sight words. They are motivated by function and purpose and a desire to get things done; so integrating academics into meaningful activities that culminate in a tangible result is much more likely to lead to success than drill and practice exercises. A Fragile X mind might think “but I just said that!” and see no point in repeating themselves. Hyperaroused by the uncertainty of an open-ended question and unable to access his/her knowledge, the student with FXS is much more likely to provide a correct response if asked to fill in the end of a sentence. For instance, “When Peter wakes up from his dream, he………” is more likely to set the stage for a correct response than the question “What happens when Peter wakes up from his dream?”
World-famous clinicians Tracy Murnan Stackhouse, MA, OTR, and Sarah Scharfenaker, MA, CCC-SLP, have worked with hundreds of children with FXS using sensory integration techniques to improve speech and attention. Empirical evidence for these methods is lacking; however, families who attend national conferences and communicate on the Fragile X ListServe frequently report success with these techniques, which include the use of joint compression, weighted vests, “heavy work,” chewy textures, and vestibular stimulation (such as swinging). For more information, see their website at www.developmentalfx.org.
Since the identification of Fragile X Syndrome as a single gene mutation, a great deal of research has ensued to understand the function of the FMR-1 protein and the biochemical ramifications of its deficiency (Hagerman, 2002). Several new drugs are approaching clinical trial status, targeting these mechanisms to correct for syndrome-specific neurological aberrations. A path leading to pharmaceutical treatment that alleviates the symptoms of FXS based on biomolecular intervention is being actively pursued, with the potential for FXS to be the first known cause of intellectual disability to be successfully treated with drugs (for more information, see www.fragilex.org and www.fraxa.org).
Carriers of the mutation have between 50 and 200 repeats of the CGG nucleotide. About 20% of female carriers experience Fragile X-associated premature ovarian insufficiency (FXPOI), which can result in early menopause. About 33% of male carriers are susceptible to a condition called Fragile X-associated tremor ataxia syndrome (FXTAS) when they are over 50 years of age, which resembles Parkinson’s disease. Decisions about whether or not to have relatives of individuals with FXS tested and if or when to tell siblings about the condition are yet another aspect of Fragile X Syndrome with which families must contend.
Resources for those interested in Fragile X Syndrome include The National Fragile X Foundation (www.fragilex.org), FRAXA (www.fraxa.org), an international listserve for family and friends of people with FXS sponsored by Emory University and FRAXA (LISTSERV@LISTSERV.CC.EMORY.EDU), and HeartShare Human Services of New York (www.heartshare.org).
HeartShare administers a contract funded by the New York State Office for People with Developmental Disabilities to provide information, referral, consultations, and staff training to support people with Fragile X Syndrome and their families. For more information, contact the Senior Director for Family Support Services at HeartShare, Laurie Yankowitz, at (718) 422-3271.