This is the first in a series of interviews of experts in the field of Developmental Disabilities. Each of the experts will be presenting at the 12th Annual Developmental Disabilities Conference at UCSF March 7 and 8. (Register now, it fills up quickly.)
Today I am interviewing Dr. Randi Hagerman, a developmental and behavioral pediatrician and the Medical Director of the MIND Institute at UC Davis. She is internationally recognized as both a clinician and researcher in the field of fragile X, the leading cause of intellectual disability and the leading known single-gene cause of autism. She is also an expert in a Parkinson’s disease-like condition called fragile X-associated tremor/ataxia syndrome, or FXTAS- conditions that she and her husband Dr. Paul Hagerman discovered. The term “fragile X” is used because of the altered appearance of the X chromosome among sufferers from the conditions. (Read Dr. Hagerman’s full bio HERE).
Dr. Hagerman will be discussing targeted treatments for Fragile X, autism, and other developmental disabilities at the conference.
I clarified some of Dr. Hagerman’s answers with information from the National Fragile X Foundation Website, the organization that she founded. If you saw my notes from the interview, you would know why.
Q) What is Fragile X Syndrome?
Fragile X syndrome (FXS) is the most common known cause of inherited intellectual disability. Symptoms of FXS include a range from learning disabilities to more severe cognitive or intellectual disabilities. Delays in speech and language development are common, as are a variety of physical and behavioral characteristics. FXS is also the most common known cause of autism or autism spectrum disorders. FXS is caused by a “full mutation” of the FMR1 Gene.
Q) My 26 year old son Matthew has autism. When he was being diagnosed as a child, he was tested for Fragile X Syndrome. Is there a correlation between the two disorders?
Yes. Whereas autism is a behavioral diagnosis, fragile X syndrome (FXS) is a medical or more accurately, a genetic diagnosis. When associated with FXS, the autism is caused by the genetic change or mutation in the Fragile X gene. This is similar to other conditions such as Down syndrome. Individuals with Down syndrome can also have other conditions, including autism, hearing loss, diabetes and other behavioral and medical conditions. If a child is diagnosed with autism and then diagnosed with FXS, he or she still has autism, it is just that the cause of their autism is known. It is no different than someone with FXS also having ADHD or any other behavioral symptom of FXS.
Many studies have evaluated the FXS-autism link over the past decade. These studies have shown the percentage of children with FXS who have autism varying from 15 to 33 percent. This range may be due to the fact that the diagnostic criteria for autism have varied and the diagnostic tools used have changed.
Since many children with FXS are interested in social interactions, they may not meet the diagnostic criteria for autism, even as they exhibit autistic-like features such as poor eye contact, shyness, social anxiety, hand-flapping and sensory issues. Autism is much more common in boys with FXS than in girls with FXS.
Approximately 2-6 percent of children with autism are diagnosed with FXS. Given the possibility of a link, it is recommended that all children with autism, both male and female, be referred for genetic evaluation and testing for FXS and any other genetic cause of autism.
Studies show that individuals with FXS who have autism can have a more significant intellectual disability (lower IQ) than those with FXS who do not have autism.
Q)Can you explain what it means to be a “carrier” of fragile X?
A carrier has an altered form of a gene that can lead to having a child or grandchild with a genetic disorder. We are all carriers of gene mutations, many of which are “silent.” This means we can pass the gene on but suffer no ill effects from it ourselves. It is only through genetic testing that we know which ones we carry. Some genes are on the non-sex chromosomes (numbered 1-22), which are the same in males and females, and some are on the sex chromosomes, which are the X and Y chromosomes.
Traditionally, a carrier of a genetic mutation is defined as a person who inherits an altered form of a gene but shows no effects of that mutation. However, in Fragile X this definition does not exactly fit, as carriers of a premutation are at risk to develop Fragile X-associated Disorders including fragile X-associated tremor/ataxia syndrome (FXTAS) and fragile X-associated primary ovarian insufficiency (FXPOI).
General population studies in both the newborn and adult populations have found that approximately 1/260 females and 1/800 males are carriers of the FMR1 premutation worldwide.
Q) Should all individuals have pre-marital screening for fragile X carrier state, given how common the carrier state is?
There are three general circumstances in which Fragile X testing should be considered:
- Clinical symptoms that suggest Fragile X Syndrome, FXTAS or infertility/FXPOI.
- A family history of fragile X syndrome, FXTAS, intellectual or learning disabilities or autism of unknown cause, or infertility.
- Family or personal history of a Fragile X Genetics and Inheritance (carrier).
Q) You’ll be talking at the UCSF Conference about your recent research of targeted treatment for Fragile X, autism and other neurodevelopmental disorders. Are there hopeful treatments on the horizon?
Yes. Elizabeth Berry-Kravis of Rush University Medical Center and I led the first “first-in-patient” drug trial examining the effects of the compound STX 209, also known by the name arbaclofen, on individuals with fragile x disorders. This *study showed that STX 209 could become an important part of the treatment for fragile X syndrome, because it appeared to improve symptoms in those with significant social deficits or autism as well as fragile X syndrome. Additional studies also are suggesting that STX 209 could be helpful for autism without fragile X syndrome. Until now, there have been no targeted treatments available for autism. This appears to be the first.
Thank you Dr. Hagerman!
*The study was conducted collaboratively with Seaside Therapeutics, a Cambridge, Mass., pharmaceutical company that is focused on translating bench research on fragile X and autism into therapeutic interventions. Seaside Therapeutics is developing the compound and supplied it for the clinical trial.
How is that for a cliff hanger?
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