Falling down

Bertrand took a tumble out of his high-chair and landed in the ER.

This lead to the world's strangest conversation:

Physician: "The CAT scan shows significantly enlarged ventricles, indicating brain damage."

Us: "OK, but what about his bones? Are there any breaks?"

Physician: "Um, his bones are fine."

In 30 years of emergency medicine, the ER doc had never seen a calmer response to the announcement of brain damage.

In more detail, the fall didn't cause the enlarged ventricles.

Actually, beyond bumps and bruises and panicked parents, the fall didn't do anything.

His ventricles (empty space in the brain) began enlarging as his white matter started disappearing about two years ago.

Unfortunately, they appear to be significantly enlarged from his last MRI in December.

Hopefully, with this new data point, we can start to measure life expectancy.

There are a few wildcards in the mix--like the stem cells and the steroids and the ACTH--but it appears we're not winning the war.

We'd been getting optimistic as of late.

We recently turned the tide on his liver damage. The ACTH stopped his seizures for almost two months, giving us a brief and unforgettable snapshot of a happy, loving baby boy.

But, it seems he's still losing white matter.

Clinically, this is consistent with our current hypothesis: male Rett syndrome from somatic mosaicism caused by a de novo mutation. (Somatic mosaicism means part of him is normal, part of him is a mutant; de novo means neither Cristina nor I are a carrier--it's a mutation unique to him.)

His next MRI will be more conclusive about the effects of our efforts, but today was a sober reminder that the clock is ticking.

FINALLY! MECP2 Gene Test Results!

"Rett Syndrome: Negative. No mutations detected in the MECP2 gene."

While I'll admit I did a 5 second happy dance, unfortunately, this is not as straightforward as it seems. (A) While MECP2 mutations count for something like 95% of all Rett syndrome cases, there are two additional genes it could be. (B) The fact that Bertrand is MALE and ALIVE and NORMAL 46XY means that if he did have Rett, he has a form of somatic mosaicism: part of his body has the mutated gene while the other part of his body does not. His blood, the part of his body on which the gene was tested, could simply be part of the portion of his body with the unmutated MECP2 gene.

Autism Comes Home

It would be accurate, if highly misleading, to say that I grew up with autism. I spent my childhood working and playing in my father's lab--my father being a neuropathologist who researches the condition. I also met a great many autistic individuals through both my father and my time at Georgia Tech.

This all said, while I realized that Bertrand exhibits autistic behavior, I did not consider him autistic. A week with my dad changed that and stripped away my last hope for normalcy. Even if no genetic condition (such as Rett syndrome) is identified, Bertrand is still autistic and pretty severely at that.

Microcephaly. It's Official.

At today's neurology appointment Bertrand's head measured (and remeasured) in the 2nd percentile while his height and weight are still in the 50th percentile. His head hasn't shrunken. It just hasn't grown in several months. This means he has microcephaly--a small head. Below is a very helpful explanation of microcephaly from an email exchange with Bertrand's genetic counselor, Rena.

"In medical terms, we use 'microcephaly' to describe a head that is below the 3rd percentile. However, "relative microcephaly" would mean smaller relative to the other measures. Because B's height and weight are around 50th %, we would say he has relative microcephaly. Usually, though, in conditions such as chromosomal breakage conditions, we are looking for true microcephaly. [...]

And, especially in the case of "relative microcephaly" we always look at the family trends. [...] What is often most important, though, is a child's trend over time. For instance, are all measures normal at birth and then does ONLY the head size become smaller? (This, of course, doesn't mean that the head is actually shrinking, just that it isn't growing along with the rest of the body). This is termed 'acquired microcephaly' which can be a type of 'relative microcephaly'. In fact, acquired microcephaly is what we generally see in individuals with a MeCP2 mutation. [...]

This would mean he has relative microcephaly, and, if the OFC dips below 3rd %, acquired microcephaly."

Moving Forward: Blood Work & 24-hour EEG

We are regaining momentum on the search for Bertrand's condition.

Yesterday, Bertrand's blood was drawn for hepatic (liver) function tests and the MeCP2 gene sequencing for Rett syndrome. Bertrand's liver function came back as still elevated: albumin 4.0, ALT 324 and AST 188.

The results for the MeCP2 will be back in about 21 days. If that comes back normal, we'll test the CDKL5 gene; one responsible for atypical Rett syndrome. Then, if that is normal, we will order testing for the final atypical Rett gene.

Frustratingly enough, in digging through my email for this post, I found an email from Dr. Vandana Shashi of Duke University to Dr. Longo from April 2009 recommending, "MECP2 sequencing if microarray is normal." Argh. She recommended testing for it almost 5 months ago and I missed it. :( I am going to walk back through her additional recommendations to make sure I haven't missed anything else.

Bertrand's 24-hour EEG should be scheduled for or by the middle of next week when Dr. Longo is back in town. This will shed a lot more light on what his brain activity looks like and what medications we should consider.