Friday, February 22, 2013

Calling All Genetic Junkies!...


I am overwhelmed with gratitude at the outpouring of love after yesterday's post, Platform. People have shared it and then those people have shared it and then those people have shared it...and on and on, creating one big circle of love around our family.  I wish all of you could see the comments on my Facebook page, on others Facebook pages, in my email, on Twitter... it would restore your faith in humanity.  I received advice, suggestions, referrals, ideas, thoughts... and just plain love and support... from all over the world.

Gavin's genetic journey has been a long and winding road.  When he was an infant, I spent a few months living in the hospital by his bed.  He was very sick with RSV and Botulism and was either lying lifeless in bed or screaming in pain.  It was then that I started googling and researching diseases, syndromes and disorders and bringing them to his Geneticists attention.  One of the first things I brought up was Mitochondrial Disease.  It has been brought up a few times since, and over and over I've been told it doesn't fit Gavin.  It's ironic that many, many people suggested Mitochondrial Disease after yesterday's post.  Even perfect strangers who came to my blog for the very first time.  

Today I set up a phone meeting with the genetic counselor at the hospital.  We spoke for an hour and went through everything that Gavin's been tested for, which is listed below.  I will also create a permanent tab at the top of the blog to have this information (and any new additions along the way) always handy.

When we got to the testing we did that supposedly "ruled out" Mito, there was a pause.  Apparently, there was part of the test that could have been seen as a red flag.  I have decided to make an appointment at a different hospital with a Mitochondrial Disease expert.  Hopefully they'll be able to fit us in soon so we can receive some guidance.  Gavin has never had a muscle biopsy, mostly because he is very challenging to sedate.  The last time he underwent sedation was for ear tube placement and adenoid removal and he ended up on BiPap in the PICU for six days.  So if we can rule anything out with blood or urine, we do.  And that's what happened with the Mito - we thought if certain things were elevated in blood or urine, they would lead us to pursue it further.  And we were led to believe it wasn't worth pursuing at the time.

Most recently, Gavin had Exome Sequencing through Baylor University.  It came back saying that he could possibly have Congenital Merosin Deficient Muscular Dystrophy, but that was ruled out by Carsten Bonnemann from the NIH.  He did not have Whole Exome Sequencing done.  I was told that it is not typically used in the clinical setting.  That the results are usually very detailed and overwhelming and hard to decipher.

I want you to know that I am taking every suggestion and referral seriously - and am grateful to each of you for taking time out of your busy lives to write to me.  Someone even suggested that we contact a medical intuitive named Anthony Williams.  We are open to this type of work so I didn't hesitate to look into this.  When I went to his website and saw his connection to Padre Pio, it felt like a sign.  Ed and I have taken many trips to the Padre Pio shrine which is not far from our hometown.  I sent our story, and yesterday's blog entry, to Anthony Williams - and he set up an immediate phone consultation with me this Sunday!  I'm really looking forward to hearing what he has to say about Gavin.  And if he has time, maybe me!

The information below is overwhelming.  Unfortunately, I've become quite the "genetic junkie" myself over the years.  It's not rare for Gavin's geneticist to open an email from me that I sent at 2am after being up researching a possible syndrome. Thank you in advance for taking a look at this and passing it on to anyone you think might have some ideas or input.  And don't forget, you can continue to vote in the Parents Magazine Blog Competition once a day until Sunday at midnight!  

This is a list of the syndromes, diseases and disorders that I researched and presented as possibilities to Gavin's geneticist.  They were either ruled out through testing or I was told none of them were possibilities.

Pitt Hopkins Syndrome
Congenital Lyme
FG Syndrome
Partial Trisomy
Wolf-Hirschhorn
Cardio-Facio-Cutaneous Syndrome
SeSame Syndrome
Russell-Silver Syndrome
Congenital Hypomyelination Neuropathy
Multiple Sclerosis
Cystic Fibrosis
Mitochondrial Disease (I've been asking about this since he was 5 months old)
Pendred Syndrome
Williams Syndrome



Below is the list that Gavin's geneticist generously typed up for me of all the testing he's had done:

According to notes from Birth Hospital: A karyotype was normal and DNA methylation to rule out Prader-Willi syndrome was negative.

2/15/2008: CJB2 (Connexin 26) heterozygous mutation c.109G>A; p.Val37Ile

2/21/2008: Signature Chip BAC Array: normal

1/28/2008 Plasma Total Lipids Very Long Chain Acids and Branched Chain Fatty Acids (screening for Peroxisomal disorders): normal

7/6/2011 Chromosome microarray through LabCorp (specifically a SNP array; results are from build 36):879 KB INTERSTITIAL DELETION OF 3P12.1->P12.1 INTERPRETATION: POSSIBLE FAMILIAL VARIANT

arr 3p12.1(85,927,122-86,806,315)x1"The whole genome chromosome SNP/CN microarray (CSM) copy
number analysis revealed an interstitial deletion of the
chromosomal segment listed below. This interval includes 1
OMIM annotated gene* (CADM2) and minimal known copy number
variant overlap.
At this time, no clinically established disorders have
been reported with imbalance in this region, although this
could change as studies progress."

Addendum: Inherited from parent 
8/29/2011: MED12 analysis (mutations in this gene are associated with FG syndrome): No mutations detected in exons 1-45 of the MED12 gene

10/11/2012: Creatine Kinase, Total, Serum 193 [normal is between: 24 - 204 U/L] 

10/22/12 Plasma Amino Acid analysis: slight elevations of leucine and valine. "Not suggestive of a specific aminoaciodopathy. Could be due to normal metabolism, patient diet, or treatment."
 
10/22/12 Urine Organic Acid Analysis: URINE ORGANIC ACID ANALYSIS OF THIS SPECIMEN REVEALED ELEVATIONS OF
GLUTARATE AND MEDIUM CHAIN DICARBOXYLIC ACIDS (ADIPATE, SUBERATE AND
SEBACATE).
THIS PROFILE MAY BE SECONDARY TO DIET (FOR EXAMPLE, FORMULA). HOWEVER, ELEVATIONS OF MEDIUM CHAIN DICARBOXYLATES CAN BE ASSOCIATED WITH FATTY ACID OXIDATION DISORDERS (FAOD) AND WITH DEFECTS OF THE MITOCHONDRIAL RESPIRATORY CHAIN. HOWEVER, NO OTHER ABNORMALITIES SUGGESTIVE OF A FAOD WERE DETECTED IN THIS SPECIMEN, MAKING A DIAGNOSIS OF A FAOD LESS LIKELY. PLEASE NOTE THIS SPECIMEN WAS DILUTE, THEREFORE ANALYSIS MAY FAIL TO DETECT CERTAIN DISORDERS WHICH ARE CHARACTERIZED BY MINIMAL METABOLITE EXCRETION.
IF CLINICALLY INDICATED, CONSIDER A REPEAT ANALYSIS OF URINE ORGANIC
ACIDS TO DETERMINE IF THESE ELEVATIONS PERSIST, AND CORRELATIONS
WITH LACTATE AND PYRUVATE LEVELS AND PLASMA ACYLCARNITINE ANALYSIS.
 
10/22/12: Plasma Lactic Acid 15.5 (Normal is between 4.5 - 19.8 mg/dL)
 
Whole Exome Sequencing did not detect a specific underlying diagnosis

This is a list of Gavin's features:

Gavin was a diamniotic/dichorionic twin gestation with one twin lost at 13 weeks
Cerebral ventriculomegaly (enlarged ventricles) noted during 2nd trimester
Born by C-Section at 37 weeks, breech, transverse lie, head was tightly wedged; circumvallate placenta with partial cord avulsion noted during delivery of placenta.
Apgars:  1 at 1 minute and 8 at 5 minutes
Born with blonde hair and blue eyes (with a Chinese father and a caucasian mother)
Eye color just recently changed to hazel/brown at 4 years old!
congenital ptosis
high arched palate 
sparse eyebrows
elongated philtrum 
epicanthal folds (but note that he is half chinese)
broad thumbs and toes
hypoplastic thumbs
tracheomalacia
he was born with sensorineural hearing loss in both ears (which has since been miraculously restored. seriously)
blonde hair (prompted prader willi which was negative)
high forehead
flat nasal bridge
simple ears with the left one minimally overfolded
extremely flexible joints
single palmar creases bilaterally
slightly hypoplastic distal flexion creases on 3rd and 4th fingers bilaterally, relatively tapered fingers
failure to thrive
esophageal reflux (severe) as an infant
mild, intermittent asthma
cerebral palsy
low tone
non verbal
flat feet
developmental delay


Whew!
If anything, I hope you leave here with a greater appreciation of how far Gavin has come despite all the obstacles thrown in his way.
Parents Blog Award Finalist




7 comments:

  1. Wow that's a long list. We are in the same boat and Andrew has a long list too. Going to see yet another geneticists on Monday probably 3rd we have seen and maybe 5 or 6 we have consulted with over email. Like you we won't stop until we find out what he has for his future. Hopefully all this increased traffic will help you find a dx. I can't help but look at the last pic of Gavin's feet, the look JUST LIKE Andrew's!

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  2. Hi Kate. I wrote yesterday suggesting the Baylor lead and haven't stopped thinking about you and Gavin since. I have just remembered a story (that you may have already heard) out of TGen, a biotech firm in Phoenix. The little girl's name is Shelby Valint and for 10 years she was wheelchair-bound and unable to speak. I don't think her symptoms necessarily match Gavin's but what is amazing is that after 10 years of testing with no Dx, TGen was able to successfully map her genome, diagnose and TREAT her! There's a FB page for her - https://www.facebook.com/Shelbyourinspiration/info. Perhaps they would be a good resource for you, if not something more.

    xoxo, Eileen

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  3. Kate, I wanted to tell you that though I know absolutely zero about genetics, I do know a great Mommy when I see one, I know we are always talking about your "Superhero" but I think behind every superhero is a super Mom. I think Gavin is one very special kid AND one very lucky little boy to have you as his Mom (and Btian, too). Hang tough, Mom. Sounds like not only are big things fixing to happen with Gavin (that you have been posting about) but sounds like big things are fixing to come your way with answers. That is my prayer for you guys tonight. I can't wait to hear how your phone conversation goes with Anthony Williams on Sunday!!!

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  4. http://www.wearechildrens.org/2012/10/mothers-determination/

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  5. Jessika Van SpronsenMarch 4, 2013 at 6:35 PM

    Have you checked his CHD7 chromosome? My son has CHARGE syndrome, and a lot of what your son has, my son also has. It is a rare genetic syndrome that can mimick other syndromes. It's worth a shot. Take a look at this site www.chargesyndrome.org and check out the definitions and genetics of it. I am sure you will see some similarities.

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  6. Have you considered DiGeorge syndrome? It seems highly likely to me.

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  7. Have you looked at deletion syndrome?

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