Genetic disorders

[lizzylou]

I'm looking for some info on genetic disorders and I'm not sure where to start.

My daughter has hypotonia (mild I guess?) and several soft markers (2 vessel cord, small VSD, sacral dimple, ear pits, high palate, feeding intolerances - all pretty benign though the feeding intolerance led to a g tube, long story!). Anyway we did genetic testing and just got the results back: normal. But the neurologist still thinks that something genetic is going on and has referred us to a geneticist. Unfortunately we don't get in for several more months.

My questions:

1. What's a good resource to learn about the basics of genetics? Books, websites, etc. I'd like to understand more but I'm just not sure where to start.

2. I should have asked the neurologist this but I didn't think of it until later - I assume that since the blood work came back normal, we've ruled out the syndromes that I've read about, like Prader Willi, Fragile X, etc?

3. When the neurologist did the physical exam she looked closely at the palms of the hands. Any idea what she was looking for? (I know, I should have asked! It's hard to keep track of so many questions).

4. Does a genetic disorder usually go along with an intellectual disability of some sort? She's had a CT scan of her brain and it was normal. She'll get an MRI but not for a few more months.

Thanks!

[askew]

I can answer a few of these. Looking at the hands, she was looking for a Palmar crease. That is where there is one line going across the hand instead of the M you normally see. Irony? My DD, who has a chromosome deletion, totally normal hands. My DS and DH both have Palmar Crease on their left hands. 

Regarding Intellectual Disability- no not necessarily, but much more likely. A lot depends on the section of genetic material missing, as in which genes are lost, size of genetic error, and somewhat on circumstance. In my DD's syndrome there is a wide variety. Maybe 5-10% have normal IQ and go through HS and college with little help. Another 40% have some learning disabilities but function okay. Then 50% have a substantial Intellectual Disability. 

If the first test came back normal, and it was not the microarray, then you have ruled out the major syndromes in their full form. You might find upon closer look that there is a smaller deletion or duplication, called a micro deletion or micro duplication. These usually, but not always, have more mild symptoms than the full syndrome. 

I don't know where to send you to learn more. Once you know something Unique is a good website to see what other people with the same error are like. The address might be rarechromo.org. 

[lizzylou]

THANK YOU!!! That is the most helpful info I've read so far!

I checked her hands and they do not have the Palmar crease... I figured her doctor would have mentioned it if something was unusual, she is pretty straightforward with me.

There's one thing I'm confused about though... You said "If the first test came back normal, and it was not the microarray, then you have ruled out the major syndromes in their full form." I think it WAS the microarray but I am not at all sure... What test would rule out the major syndromes in their full form?

Again, thanks. I am off to check out the website you mentioned.

[askew]

Originally Posted by lizzylou 

THANK YOU!!! That is the most helpful info I've read so far!

I checked her hands and they do not have the Palmar crease... I figured her doctor would have mentioned it if something was unusual, she is pretty straightforward with me.

There's one thing I'm confused about though... You said "If the first test came back normal, and it was not the microarray, then you have ruled out the major syndromes in their full form." I think it WAS the microarray but I am not at all sure... What test would rule out the major syndromes in their full form?

Again, thanks. I am off to check out the website you mentioned.

Usually the first test they do is the basic chromosome test. This one is not super sensitive, but will show you all the larger deletions or duplication. Like most of the syndromes that have names. The microarray is very sensitive, costs about 4K, and takes 4-6 weeks to get the results. Some insurance companies will not cover it. Mine would not. If it was the microarray and it came back normal, then there is likely not a genetic error, or it is so small and rare the test is not sensitive enough to pick it up. 
 

[lizzylou]

Thanks again! I think it *was* the microarray. It took 4 weeks and the doctor said that it was expensive and she had to get it preapproved by insurance.

I am going to call tomorrow to find out for sure if this was the test we did. I didn't realize there were so many different types of testing.

[lizzylou]

The doctor confirmed that it WAS the microarray test that we did. She still thinks it's something genetic though. 

I sent in all the paperwork that the geneticist requested... hoping to get an earlier appointment with him.

[Lollybrat]

The Microarray is a very in-depth test. Even so, there are several things it cannot pick up. These include:

- balanced translocation (where all the genetic information is there, but in the wrong order - sometimes this has medical consequences, but often it doesn't)
- micro deletions/duplications that are below the sensitivity level of the test
- single gene mutations

I'm sorry to hear that testing hasn't given you any answers into your daughter's situation. I can tell you from personal experience that sometimes even getting a result doesn't give you any answers. My son had a microarray done let summer and we discovered that he has a micro deletion on his 19th chromosome. His micro deletion is so rare that the doctors are unable to tell us the clinical significance of it and how it impacts his issues (autism, hyperlexia, dyspraxia, albinism). We can only hope that future research will one day lead to more insight into his situation.

Hugs.