171: Fragile X Syndrome Day: Clinical Challenges, Care Strategies, and Emerging Therapies

Thank you for joining us today to talk about Fragile X Syndrome in honor and recognition of Fragile X Syndrome Awareness Day.

My first question for you on this topic is, what are some of the biggest challenges clinicians may face in recognizing and diagnosing Fragile X Syndrome, particularly in patients with more subtler atypical presentations?

That's a really great question.

You know, Fragile X testing, which is still clinically southern blot in PCR, is pretty much recommended for all children with developmental delay and or an autism diagnosis.

You know, I think that while we have improved availability of testing in that, you know, over the last 20 plus years of my career, you know, including state insurance payers and other third party payers have generally been covering Fragile X testing.

You know, we do miss some cases.

I mean, some people do not get access to genetic testing, not only Fragile X, but other indicated testing.

And I think the group that, you know, with as you refer to some of the subtleties are the girls and females with Fragile X. that may have kind of mild developmental impairment but, or maybe have no impairment at all and will not be diagnosed until they are found to have, you know, other relatives with Fragile X syndrome because it's an excellent condition.

You know, males are much more significantly affected and, you know, really on average, you know, one out of two females would have clinical effect, but the true representation of females is almost infinite variation from potentially significant or severe impairment mimicking male impairment to no impairment at all.

So it makes the female diagnosis certainly tricky and kind of lessens some of their access to diagnosis.

Again, unless they have first degree relatives with Fragile X, a lot of times females may not be caught.

Thank you.

And my next question talks a little bit about, you know, the genetics of this condition.

So how do you approach counseling families on genetic testing and, you know, cascade screening once Fragile X syndrome is confirmed?

Yeah.

So once Fragile X syndrome is confirmed in an individual, we really try to offer testing as broadly as possible.

It's excellent triplet repeat expansion disorder.

So it's most commonly passed on from a pre-mutation mother who would have inherited really essentially the exact same number of CGG repeats most often from her father.

Though some cases we have full mutation moms.

And the full mutation moms may have had some mild developmental effects or really no developmental effects.

They may not even know they have the full mutation until they have an affected child.

We're very keen on not only screening for full mutations throughout the family, but also for carrier status.

And we offer that broadly for affected relatives.

Fragile X carriers are at risk for Fragile X tremor, ataxia syndrome, much more common in males than females.

And carriers also have other risks in women of early ovarian insufficiency and increased rates of other diseases.

Thank you for joining us today to talk about Fragile X Syndrome in honor and recognition of Fragile X Syndrome Awareness Day.

My first question for you on this topic is, what are some of the biggest challenges clinicians may face in recognizing and diagnosing Fragile X Syndrome, particularly in patients with more subtler atypical presentations?

That's a really great question.

You know, Fragile X testing, which is still clinically southern blot in PCR, is pretty much recommended for all children with developmental delay and or an autism diagnosis.

You know, I think that while we have improved availability of testing in that, you know, over the last 20 plus years of my career, you know, including state insurance payers and other third party payers have generally been covering Fragile X testing.

You know, we do miss some cases.

I mean, some people do not get access to genetic testing, not only Fragile X, but other indicated testing.

And I think the group that, you know, with as you refer to some of the subtleties are the girls and females with Fragile X. that may have kind of mild developmental impairment but, or maybe have no impairment at all and will not be diagnosed until they are found to have, you know, other relatives with Fragile X syndrome because it's an excellent condition.

You know, males are much more significantly affected and, you know, really on average, you know, one out of two females would have clinical effect, but the true representation of females is almost infinite variation from potentially significant or severe impairment mimicking male impairment to no impairment at all.

So it makes the female diagnosis certainly tricky and kind of lessens some of their access to diagnosis.

Again, unless they have first degree relatives with Fragile X, a lot of times females may not be caught.

Thank you.

And my next question talks a little bit about, you know, the genetics of this condition.

So how do you approach counseling families on genetic testing and, you know, cascade screening once Fragile X syndrome is confirmed?

Yeah.

So once Fragile X syndrome is confirmed in an individual, we really try to offer testing as broadly as possible.

It's excellent triplet repeat expansion disorder.

So it's most commonly passed on from a pre-mutation mother who would have inherited really essentially the exact same number of CGG repeats most often from her father.

Though some cases we have full mutation moms.

And the full mutation moms may have had some mild developmental effects or really no developmental effects.

They may not even know they have the full mutation until they have an affected child.

We're very keen on not only screening for full mutations throughout the family, but also for carrier status.

And we offer that broadly for affected relatives.

Fragile X carriers are at risk for Fragile X tremor, ataxia syndrome, much more common in males than females.

And carriers also have other risks in women of early ovarian insufficiency and increased rates of other diseases.