Do I or Don't I?

Time for an update on all things chaotic. We learned in December that Evan does in fact have FSHD. This was not a shock really. He does not seem the least bit phased by the news, perhaps he sees this as another challenge, or perhaps something that makes him uniquely Evan. Typical Evan, he proceeded to explain how DNA works to Dr. Smith, something about RNA and proteins and binding... He lost me. Apparently it was a question from his Honors biology final in December.  The kids are fine for now and only time will tell where this disease will progress for them.  I worry mostly because they are young so I suspect they will be on the symptomatic side.  In Megan's case, her clinical report said "Facioscapulohumeral Muscular Dystrophy, early onset."  Hmm, not sure if "early onset" is a term to say this is earlier than normal for this diagnosis, or a term to mean, she is still very early in the disease progression.

Dr. Smith offered to see me as a patient as well even though he is a "Pediatric" Neuromuscular doctor.  I had a great consult with him just before the New year. I can't say enough great things about this doctor, finally a doctor who listen's to what I am saying, answers my questions and genuinely seems to care. It appears that the symptoms I have been having for perhaps 8-10 years now are in fact consistent with FSHD. They are also symptoms of several other things (MS, Lyme, Lupus, RA, Fibromyalgia) which makes my diagnosis complicated. Certainly having 2 children with a clinical diagnosis of FSHD which is a genetic disorder makes my diagnosis much more likely. My clinical findings were "subtle" weakness in some key areas. The "plan" was for me to have the DNA test after Megan's results came back.  Like many plans, sometimes things don't go as planned.

To add a level of confusion and complication to the mix, we subsequently found out that Megan was DNA negative for FSHD1. This means that she and Evan presumably have FSHD2.  Dr. Smith was clear with me that regardless of the test results, Megan has FSHD.    Unfortunately, this means that testing me would also produce a negative result. FSHD2 does not yet have a commercially available test.  In fact, only about 5% of FSHD cases are type 2.  From everything I can find on this topic, it does appear that FSHD2 is also associated with chromosome 4, same region.

This links to the best document I have found so far related to
FSHD2; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2974464/ . This study
outlines the specific findings in FSHD2 and of course how type 1 and 2 are
phenotypically the same. A few things this study seemed to highlight for me
include:

1) Both types of FSHD require a permissive Haploytype 4A161 (or 4A159, 4A168). 
It was not clear if the D4Z4 contraction noted in FSHD1 is ever found in
conjunction with a non-permissive haplotype, if so, this would suggest that
some people with positive FSHD results and no clinical symptoms could actually
not have FSHD?

2) Both types require that the D4Z4 is hypomethylated.  I looked this up on google, it means that some of the DNA is not as "specified" as it should be and this affects gene expression.

• In FSHD1, the contraction (smaller repeat size) of the D4Z4 appears to be the cause of hypomethylation
• In FSHD2, D4Z4 hypomethylation cause is still unknown
• Methylation affects gene expression, not enough DNA methylation of D4Z causes the cascade of events (DUX4 toxic protein expression) leading to FSHD.
• If your D4Z4 is large enough, you may not be symptomatic even with a permissive haplotype and hypomethylation of D4Z4

3) D4Z4 Repeat Size is important for both type 1 and type 2 

• FSHD2 D4Z4 presents with "medium-sized" 4A161 D4Z4 repeats with an average of 16 repeat units, (16 x 3.3kb) + 5 = 58kb size
• FSHD1 is 1-11 repeat units
• Controls average 28 repeat units (97kb size)

4) FSHD2 shows both dominant inheritance and recessive inheritance

• Does this mean the permissive haploytype can be inherited from one parent, and the "cause" for the hypomethylation from the other parent?

I have talked to the LAB and the genetic counselor there is talking with the doctor in the lab to see what else they can do.  We know in studies that they can check for the permissive haploytype as well as the level of hypomethylation, perhaps the lab has that ability?   Additionally, I have asked for a specific D4Z4 repeat size for Megan, not just a "greater-than" the required number for FSHD1.  The genetic counselor suggested that the lab may offer a free test for Evan to show that both kids in fact do "match" genetically on chromosome 4.  If they match, perhaps they can check my sample (already in their hands) and determine if I "match" the kids in the D4Z4 region.  If I match them and they have a strong clinical diagnosis, that would perhaps confirm my own status.

Meanwhile, as the lab looks into what more they can do, Dr. Smith will take our case files to his colleagues in Minnesota this week when he travels there.  His assistant/nurse has told me that he plans to also talk to a genetic counselor.  They asked me to come back next week for another consult to discuss this further. 


Some people have questioned, why does it matter.  I guess that is a really hard thing to explain but for me, having a name for something that has sent me from one specialist to another for the last 8 years is immensely important.  Because when they find a "cure." I need to know if I should get in line with the kids :-).  And for the record, I am fully expected them to have a cure in the near future.  I think also, it gives me a group of people to relate to and a place to find support.  Without a diagnosis, one can be labeled a hypochondriac.  I have felt in some ways that the way I feel does not matter, that maybe it is all in my head.  I hope I can find an answer. 

On an entirely different subject, Ryan is out of jail and seems to be doing well.  The court is keeping him busy to include intensive counseling 3 mornings per week, group once per week, court and probation meetings weekly, 3-4 UA's every week.  In addition to this, his sober house requires AA/NA meetings every day.  Next step is a job.

Brendan has completed his first semester of college and has done well.  He is a pure joy and I am very proud of him.  He is off in Florida for a visit with his girlfriend Amber before the spring semester starts.

Alan is amazing, what more can I say there!  He has received a promotion in just a few months with ITT.  He has been working 72+ hours per week for about 2 months now while filling in as site lead for the network group at Bagram in Afghanistan.  I miss him and it is hard not to be able to discuss all this MD/FSHD stuff in detail with him.  I know it is harder on him being so far away and worrying about the kids.  We are hoping for a visit home in March!  In just a few more months he will have to start looking for a job for when he returns in September.