The Road to the Diagnosis

The Road to the Diagnosis
Blog entry written on June 24, 2011

Caroline was born in January 2010. We were in love the second we met her. She was sweet, bright, easygoing, and observant from the very beginning. Caroline’s birth weight was a bit on the lower side at 5 lbs 11 oz, but aside from having to work a little harder at getting her weight up, the early infancy stage was easy and uneventful. She hit all her milestones on time until about 6 months. She even said “mama” for the first time at 5 ½ months.

Around 7 months, we noticed that the development of her gross motor skills had slowed down a bit, but not enough to raise serious concern. Caroline’s growth rate went from the 1st percentile at birth to the 90th + percentile by the time she was 6 months so we figured her slight delays in crawling were an issue of being a bigger baby and hating “tummy time.” In fact, in spite of keeping her off her back by repositioning her during sleep and pushing for tummy time, she ended up with a bad case of plagiocephaly and brachycephaly (aka “flat head” syndrome). She was in a Doc Band for 4 months to help improve the shape of her head.

At 9 months, Caroline still wasn’t crawling so her pediatrician suggested we contact Early Intervention services. Her evaluation was conducted at 11 months and services began a couple of weeks after her first birthday. Before she started physical therapy, she could stand with assistance for a couple of seconds, but was pretty much confined to the sitting position without being able to reach to her sides. Three months into therapy, she was: standing for long periods with support; rolling to get to things; creeping backwards and sideways; getting up to sitting with minimal assistance; and pulling up to standing with help. Caroline had finally developed the strength (and motivation!) to crawl, but the coordination necessary to move forward was still missing.

In mid-April, at 15 months, Caroline began a repetitive movement with her hands that involved “clapping” and clasping. These movements were subtle at first, but my heart sank the first time I noticed them. The repetitive behavior was a sign that we were dealing with more than just gross motor skills delays. We started consulting different specialists and learned about the possibility of Rett Syndrome. We were stunned and in disbelief when we read about the horrific progression of the disorder. Still, we held hope that we were simply in the process of ruling out the “worst case scenario.” We desperately wanted to believe that her issues were due to her inability to crawl or walk and explore the world like a typical 15-month-old. In the following month, the movements became constant and she began to lose the ability to use her hands to pick up objects, play with her toys, self-feed, and hold her bottle. We also noticed that she had lost almost all of her words, including “mama” and “dada.” She was verbal early on and communication had always been her strength. Mike and I had very dark days filled with grief and anxiety as we watched Caroline struggle with the loss of these skills.

Today, Caroline was diagnosed with Rett Syndrome based on clinical observation alone. We are currently undergoing a series of tests to determine the underlying genetic cause for her condition. It’s hard to describe the level of sorrow we feel and will probably continue to feel for a long time. Caroline’s health is compromised and the future we had envisioned is suddenly crushed. We are facing an unexpected and painful turn in our lives, but Caroline gives us strength. She is a loving little girl who fills our hearts with love and joy. We are surrounded by the love and support of family and friends. We have wonderful doctors, therapists, and teachers working with Caroline so that she can continue to work on preserving skills and make progress in all areas of development. We are also educating ourselves and reaching out to all appropriate resources to ensure that we fully understand and meet her needs. Caroline is going to have a happy and rich life filled with tons of love.

We just need to keep working on reprogramming our expectations and definition of “normal.”

Caroline around the time of the diagnosis, June 2011


Blood test results
Blog entry written on July 14th, 2011

Last month, Caroline received the clinical diagnosis for Rett Syndrome based on meeting full essential (and most of the supportive) criteria for the disorder.

Caroline's first blood test involving the full gene sequencing did not detect the MECP2 gene mutations associated with about 85% of Rett Syndrome cases. In 15% of the cases, the disorder is caused by deletions in the MECP2 gene. Today, Caroline's geneticist called to inform us that Caroline's second blood test revealed a heterozygous deletion of exon 3 and a partial deletion of exon 4 in the MECP2 gene.

The MECP2 gene, which is located in the X chromosome, regulates the protein in our bodies that helps us talk, walk, and do everyday things we sometimes take for granted. Mutations or deletions in the MECP2 gene disturb the function of those skills (though mutations in a couple of other genes including CDKL5 and FOXG1 have also been implicated in variant Rett cases). The "glitch" in the gene results in Rett Syndrome.

I already knew Caroline had Rett Syndrome, but hearing the exact molecular reason was still sad. I started thinking about how we went through our entire pregnancy and Caroline's first year not knowing what was happening to her body. We never thought that the various symptoms--gross and fine motor delays, teeth grinding, sleeping issues, reflux, etc.--were all pieces of the same puzzle. Nobody did. It wasn't until Caroline started to lose her words and ability to use her hands that it became clear that we were dealing with something much more serious than we ever imagined.

The disorder, however, doesn't affect Caroline's intelligence or her ability to love. She is an affectionate and sweet baby. She understands and will always understand what is said to her because the brain remains intact. In fact, there are a number of ways to communicate involving eye gaze, which we are already starting to figure it out. If we ask Caroline to point to her mommy, daddy, grandmom, dog, etc., she looks in the right direction. There is also technology that enables the use of eye gaze to act as a "mouse" to point to words or images on a computer screen. I am excited about the possibilities around communication!

(Further explanation from the International Rett Syndrome Foundation website)
The link between Rett Syndrome and the MECP2 gene :
Rett syndrome is primarily caused by a sporadic mutation in the MECP2 gene on the X chromosome. The MECP2 gene makes a protein, also called MeCP2, believed to play a pivotal role in silencing, turning off or regulating the activity of other genes. The MECP2 mutation (change in the gene) causes the turn-off/regulatory mechanism to fail, allowing other genes to function abnormally. So, RTT is a genetic disorder of developmental arrest or failure of brain maturation. This is thought to occur when subsets of neurons and their connections (synapses) are disrupted during a very dynamic phase of brain development. This deviation occurs at the end of pregnancy or in the first few months of life during the critical phases of synapse development. How mutations in MeCP2 lead to RTT is not well understood but is the focus of intense research.
Why development is normal in the first few months:
RTT results from a chain of events beginning with the MECP2 genetic mutation. Mutations occur naturally in everyone all the time and most do not cause problems. The MECP2 mutation results in a shortage or absence of normal MeCP2 protein needed to regulate or direct other genes. These other genes affect or control the normal development of selected regions of the brain responsible for sensory, emotional, motor and autonomic function during the critical period of infancy when important milestones are expected to be achieved. Development appears to be normal in early infancy until the MeCP2-related regulation or control is needed. Without these controllers, selected regions of the brain do not develop properly. This explains why the child appears to be developing normally in the first months of life.