The misdiagnosis of fragile X

Fragile X is a genetic condition involving changes in the X chromosome.  It is the most common form of inherited intellectual disabilities in males and a significant number of females.  It is thought that 80 - 90% of those affected with fragile X are undiagnosed or misdiagnosed.

Fragile X is caused by a change in the FMR1 gene, when the gene’s code is repeated on the fragile part of the X chromosome.  The more times the code is repeated the more likely there is to be a problem. The condition is caused by a trinucleotide repeat. People without fragile X typically have 5 to 45 repeats. Carriers have 55 to 200. The full mutation happens after 200 repeats, when the gene becomes methylated and stops sending its message. Normally, the FMR1 gene makes a protein needed for brain growth.  Having a defect in the gene makes it produce too little or not enough of the  protein.   Males and females can both be affected, although boys only have one X chromosome, a single fragile X is more likely to have a higher rate of severity.  

Approximately 25-35% of cases are misdiagnosed as autism because they share many of the same behavioral issues.  Poor eye contact, social awkwardness, repetitive motions and speech, and hand-flapping or biting.  Children who have fragile X will need to be treated for autism in addition to the treatments they receive for fragile X.  Children who also have autism have lower cognitive abilities than those with fragile X alone.  Why some have more severe deficits causing autism is not known.  However, most children with fragile X are not autistic.  They show interest in others, enjoy social situations, although poor eye contact and hand-flapping or biting are seen in 50-90% of children with fragile X even without being autistic.  

In older persons, fragile X has also been misdiagnosed as Parkinson’s Disease.  Men who are carriers of fragile X syndrome but not affected can develop a pseudo-Parkinson's disease when they reach their 50s, according to a published report from the University of California.  Previously, it was thought that these men were spared any consequences of fragile X syndrome because they had a mutation that wasn't severe enough. The fragile X gene (FMR-1) is located on the long arm of the X chromosome, and it is a relatively short gene. In a carrier, it is slightly elongated, with some repeats. In someone more severely affected, it is even more elongated.  According to estimates of the fragile X chromosome prevalence, 1 in 800 men is a carrier but not affected.

Autism and fragile X also have in common attention deficit/hyperactivity disorder (ADHD).  70-90% of males and 30-50% of females will be affected by ADHD as well as sensory problems.  Such as sensitivity to light, touch and sounds.  Females have less mood instability, aggression and hyperactivity.  More often shyness, and social anxiety causes withdrawal or even the reluctance to speak.  

Previous screening studies have shown that 2.5% to 6% of boys with autism have fragile X. (Brown, Jenkins et al. 1986; Bailey, Phillips et al. 1996; Hagerman 2002) Therefore it is thought that, all children with autism and or intellectual disabilities should have fragile X DNA testing. Such screening may also identify individuals with the fragile X premutation in association with autism and there are current evaluations of the additive effect of the premutation which can be associated with mild gene dysfunction (Tassone, Hagerman et al. 2000).

In summary, the association of fragile X and autism is a strong one which requires assessment in each child.  At current date there is no cure just treatments.  Speech, occupational, behavioral, and language therapies can address some of the physical, behavioral, and cognitive aspects of fragile X.  

[888mom]

If you take your child to a developmental pediatrician or pediatric neurologist, they usually do genetic testing (drawing blood) to rule out things such as fragile X.  Of course, I didn't find out that my health plan didn't cover the genetic testing, so you would want to look into that and prepare yourself financially for tests like that (I still would have done the tests, but would have saved money up and asked about the cost upfront).