Tuesday, September 23, 2008

Our Journey with CDKL5, Atypical Rett Syndrome

Welcome to our site. I am saddened that we meet this way, but grateful that you have found us. We are a small but growing group of people that share similar journeys of how our children that have been affected with deletions of their CDKL5 gene. You will find much support from the families here. Receiving a diagnosis, then finding this site has helped us in more ways that one can imagine. Speaking to, venting, crying, listening to, and just knowing that the families here fully understand our every day hardships and struggles has helped me every day.

I am Lisa and my 13-year-old daughter Alexis has been diagnosed as having deletions of the CDKL5 gene, Atypical Rett Syndrome, Lennox Gastaut Syndrome and deletions on her Xq22.2 gene. Alexis was diagnosed on April 30, 2008 when she was 11 ½ years old. We live in New York, USA. I am not a carrier and neither is the father.


CDKL5 is a gene that is found on one of our sex chromosomes called the X chromosome. The letters are an abbreviation of the scientific name of the gene which describes what it does. The long-winded name is cyclin-dependent kinase-like 5. The CDKL5 gene was previously called STK9 and sometimes people think that the two genes might be different but they are in fact the same.

The CDKL5 gene provides instructions for making a protein that is essential for normal brain development. Although little is known about the protein's function, it may play a role in regulating the activity of other genes. The CDKL5 protein acts as a kinase, which is an enzyme that changes the activity of other proteins by adding a cluster of oxygen and phosphate atoms (a phosphate group) at specific positions. Researchers have not determined which proteins are targeted by the CDKL5 protein.

Mutations in the CDKL5 gene are have been found in girls with Atypical Rett Syndrome and boys and girls with X-linked infantile spasm syndrome (ISSX), West Syndrome and early onset seizures.

To date one girl with a milder form having moderate intellectual delay and autistic features with no seizures or physical disabilities has been diagnosed.

Some CDKL5 mutations change a single protein building block (amino acid) in a region of the CDKL5 protein that is critical for its kinase function. Other mutations lead to the production of an abnormally short, nonfunctional version of the protein. Researchers are working to determine how these changes result in seizures and the characteristic features of Rett syndrome [RTT] in affected children The involvement of CDKL5 in RTT seems to be explained by the fact that it works upstream of MeCP2, the main cause of RTT.

At the moment testing for CDKL5 is limited to children with a diagnosis of Rett Syndrome who have been tested negative to the Rett Syndrome gene MECP2 and a handful of children who have severe early onset Infantile Spasms or epilepsy onset within the first few months of life.


Alexis was born on July 19, 1996 and appeared to be a normal healthy baby girl. Our journey began when Alexis was only 10 days old. Alexis started to cry and was unable to be comforted. The pediatrician told us that it was colic, to switch the formula, and to deal with the crying because in time the crying would go away. Well they were wrong because Alexis cried until she was around 5 years old.

In October of 1996 when Alexis was 3 months old she threw a fit, no one saw but myself and I figured it was related to the crying spells. Alexis did the same thing the following day and I called 911. Alexis was having seizures. The doctors think Alexis may have been having seizures all along or the crying was neurological discomfort. They took blood work, performed a spinal tap to rule out meningitis, and did a cat scan. We spent our first Halloween together in the hospital wearing a clown suit and an EEG to monitor the seizures. This is when our lives were turned upside down. The neurologist put Alexis on Dilantin and told us that she would probably grow out of the seizures. They were wrong.

When Alexis was 5 months old, she stopped responding to light and wasn’t consistently tracking objects anymore. The Neurologist said that she was visually delayed and not to worry. Well, she was wrong again. Soon after having seen several Opthomologist’s and having a VER & ERG we learned to find out that Alexis is cortically blind. The EEG’s showed the seizures start in the visual part of Alexis’s brain then spread out to the rest of her brain. This is why Alexis’s vision is impaired. To this day we still do not know what Alexis can see.

So now all the testing and procedures begin to find out what is happening to my daughter. Alexis had so much DNA testing done at all different times with no luck of finding a diagnosis. She had Cat scans, X-Ray’s, MRI’s and a PET Scan. GI studies done such as Barium Swallow and Upper GI series. Alexis had muscle and skin biopsies done a few times. They did a series of Spinal Taps due to a small amount of excess cerebral fluid and they wanted to see if a shunt would help. In order to further investigate if a shunt would help an ICP (inter cranial pressure testing) was done. The excess fluid was a small amount. We didn’t further pursue the shunt. As for visual testing, Alexis had a VER and a BER. Alexis also had an EMG (nerve conduction study). Cardiology testing consists of EKG’s and Echo Cardiograms. Alexis had surgery to close a very large hole in her heart.

Alexis had numerous EEG’s done to monitor her seizures. We have tried 12 different seizure medications and the Ketogenic Diet. Nothing has helped to control the seizures. Currently (2010) for the seizures Alexis is on Depakene 2 times a day. At the onset of a seizure the VNS (Vegal Nerve Stimulator) is swiped and at when the seizures is at 5 minutes the Diastate is administered.

Alexis’s is severely developmentally delayed and is at the level of a 6-month-old baby. She has uncontrolled seizures, no hand skills other than hand wringing and mouthing. She is hypersensitive to touch, and disliked to have her hair brushed when she was little. Alexis is cortically blind, has gastro reflux and constipation. She has small cold feet. She used to grind her teeth. Alexis had laughing spells and crying spells for years. Alexis has poor muscle tone and autistic like traits. She cannot walk and is wheelchair bound. Alexis can get herself into a seated position but doesn’t have the strength to stay up for long. Alexis still wears diapers. She doesn’t speak, but at times will make sounds especially when she is hungry or bored. Alexis wears orthodics and is currently going through Botox treatments to see if this helps. Alexis wears soft arm splints to keep her hands out of her mouth, to avoid skin breakdown, and prevent hurting her eye with her little fingers. She was diagnosed with Scoliosis in 2008 and may need surgery in the near future. Alexis lost the ability to show emotion and pain. We are constantly reminding everyone that she can feel everything and to be gentile.

Because Alexis is dependent for her every daily need she lives in a 24-hour residential nursing facility with a total of 7 girls since she was 5 years old. She attends a day program Monday through Friday where her therapies are received such as Physical, Occupational, Speech and Vision. Alexis spends every weekend home with her family that was recently renovated with a handicapped accessible shower and bedroom to suit her needs.

In March of 2006, I moved Alexis to new residential home to bring her closer to her family. The staff was not properly trained on how to feed the children. She was losing weight and not even a month later a Mic-key feeding tube was placed. The goal was to feed her by mouth and if they were not successful to resort to the feeding tube. In time all feedings were done by the Mic-key due to signs of possible aspiration. Now in 2010 we are pending a swallow study to see if Alexis can begin to eat again by mouth.

Again, welcome to our group. We look forward to hearing about your journey and sharing more of ours with you. Please do not hesitate to share your experiences with us and to ask us about ours. We are all we have at the present time and we need each other to support and guide us in our journey as we wait for research and a cure. We are here to help each other, offer advice to each other, encourage each other and educate each other. Each and every one of us has experiences that may help another family in need. Please do not hold back. We want to hear everything you have to offer.

7 comments:

maddalena said...

Ciao io sono una mamma italiana con una bimba candidata alla sindrome di rett. Non ha mutazione del MECP2 esame ripetuto per ben 5 volte! Ora faremo l'esame del CDKL5 e sono molto tesa! Mia figlia non ha per ora crisi epilettiche anche se mi hanno detto che le potrebbero venire... io spero di no! Voi conoscete bimbi con mutazione del CDKL5 senza crisi epilettiche?
Il dott.Elia mi ha consigliato di far eseguire l'esame a mia figlia... perchè ci sono dei casi senza crisi epilettiche e ha anche aggiunto che ci sono sicuramente tanti con mutazione CDKL5 senza essere diagnosticati... per lui c'è ne sono molto di più...
Sono triste... a pensare che mia figlia una bimba sana con questa "maledetta" malattia non ci sia una cura. Mi deprime molto!
Quando vedo Asja sorridere il mio dolore per un attimo ... scompare!
Mamma di asja

e-mail birillodale@live.it

emanuela said...

there are boys too, with cdkl5 disease.
Not every children with cdkl5 have epilepsy
There is another web site: www.cdkl5.org
bests
emanuela

Floris said...

Dear Lisa and Alexis Amber,

We've read your story and we boh feel that you have gone (and still are going) through a lot of hardship together. We recognize a lot of the things you're writing. Our son Floris is also diagnosed with CDKL5 and has all the symptoms except for the severe seizures. Some convulsions (mostly during the night), but not the Grand Mals we hear a lot about. Yet ...

Bye, Peter and Paulien van Helsdingen, the Netherlands

emanuela said...

there is a cdkl5 association: cdkl5 associazione di volontariato. We think the only one in the world. We will work to make find the cure to the scientist before every ideas (HOPE to save our children too)
www.cdkl5.org

chris said...

i have aspergers and charcot marie tooth i am almost 30 ,i know first hand the daily pains of being a special needs person growing up with multiple disabilities:dealing with orthodics ,diapers and diaper companies ,drs p.t./o.t. its not easy but gets easier never loose hope and keep fighting god bless!

Emma Reynolds said...

My daughter was just diagnose with CDKL5. she has partial replications with mutations.. at any rate we plan to move to upstate ny when i retire... think homer... anyway was wondering if you knew of any good hospitals or clinics we could go to.

Anonymous said...

Hello I'm Emma from the United Kingdom I have just found out that my daughter Megan who is 2 years old has atypical Rett syndrome , she can not talk and has the mental age of a six month old baby . She started to go back wards at the age of 9 months but as a baby she never cried and when she hurt herself never cried, she wears pedro boots and when I found out after loads of tests done over a period of a year I just broke down.
Reading what you have put has made me feel better knowing that I'm not on my own
Thanks