New diagnosis from genetics team at Cedar Sinai

We met with the genetics team, led by Dr. Graham, at Cedar's last Friday. They seemed to really know their stuff. As I might have posted before, he was referred to me by Dr. Dobyn's in Seattle, who specializes in brain malformations. It was a good meeting. Mike came home just in time for it so we both were able to try and understand all they were saying. He also recorded it to. Basically, it is somewhat good news, at least not more bad news.

What Dr. Graham feels Ian has is what's called Macrocephaly-capillary malformation syndrome (M-CM). He also kind of falls into these other two categories: Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) (this is the proposed new name for the M-CM syndrome based on new findings Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (MPPH) (which is what Dr. Dobyn's originally thought. Dr. Graham is thinking he's not "heavy on the Polymicrogyria" and of course he doesn't have an extra digits, although they pointed out he's got some foot condition that creates a bit of extra skin connecting the middle three toes.

So what does this mean to us, or more importantly to Ian and his future. It's hard to understand really. I guess with M-CM there's a connective tissue disorder component. This is presenting itself in his lower tone, his big toe that can bend completely forward and his Pectus Excavatum. They explained so much but I need to listen again to truly understand. (I did listen again and my notes are below. I'm too tired to finesse them)

http://www.ncbi.nlm.nih.gov/pubmed/19353582

http://www.m-cm.net/blog/tag/genetics

Mixture of low tone and joint laxity. As their muscles get stronger and the tone gets better, underneath it all the tissues are lax. The dilated great vessels are because those muscles are lax as well. He was wondering how they can strengthen those muscles.

In these cases, including Ian's they see a mosaicism www.ncbi.nlm.nih.gov They've found a gene in Ian that seems to be altered in some but not all of the cells. Dr. Dobyns wants to call is MCAP.

It effects his skin, his joint, fluid drained out and left a lot of extended vessels in the skin, possibly capillaries as well as lymphatics. Maybe when he starts

He's going to go over the MRI cold with Dr. Preston, the Neuroradiologist at Cedar's.

Straight forward Macrocephaly, Megalencephaly Capillary Malformation http://www.m-cm.net/blog/tag/genetics

with an especially noticeable connective tissue issues. He has mild webbing in the 2, 3 & 4 toes, joined together in the middle with extra tissue.

One of the things they worry about in early childhood with the rapidly growing brain is that part of it gets stuffed into the spinal cord. Chiari One Malformation http://en.wikipedia.org/wiki/Arnold–Chiari_malformation . They need to look to see if there's any sign of it.

Normally our sutures don't close entirely until our 40's but since we shunted him it caused his to close. His skull is responding to the rapidly growing brain but usually the

What we need to look for have some rhythm disturbances, which is a connective tissue thing. When he first started writing about this, he thought it was pressure on the brain stem but now he feels it's more of a ct thing.

They of course keep track of MRI's. Most of his rapid brain growth is in the first 18 months so his growth should go with the curve now.

If his PMG is subtle, and this develops during the third trimester so it will not change at this point. It's very different than the PMG that shows up in other abnormalities. We need to put that out of our head. He does not have severe PMG. All that happens is he has some extra cortex wrinkled up in his fissures. That's why he doesn't want to add it to the name of the syndrome name. Maybe it's there but it has minimal clinical significance. He wants to look at his EEG's. We need to get them to him.

He expects them to be mildly disabled from a cognitive standpoint. They need to do more research on the condition. 1997 is when they put the pattern together. Many kids that have this disorder had been lumped into other disorders.

Speech is slow for these kids but he feels that he will speak.

If it grows too much without any room it might cause more wrinkles causing seizures.

He feels Ian possibly didn't need the shunt. After the shunt the brain didn't stop growing but the ventricles compressed due to the shunt.

If there was significant herniation someone would have probably noticed it.

The joint laxity continues to persist. The reason these kids walk late is the joint laxity, low muscle tone and the size of his head. His knee's will buckle when he stands. His body needs more exercise to strengthen muscles. Suggest to have gait training.

Despite all his problems he's done really well.

They need to look at his saliva and his blood to see more.

He's thinking the dilated great vessels are part of his connective tissue issue which causes problems, possibly like Pulmonary Hypertension.

His Capillary Malformations are very subtle.

His teeth not having enamel he has not seen in other kids with this condition.

http://www.ncbi.nlm.nih.gov/pubmed/19353582