| A STUDY OF THE ASSOCIATION OF
NEUROFIBROMATOSIS TYPE 1 AND AUTISM
– By Dr. Dorota Kwasnicka and Stephen Scherer
7
Department of Genetics, Hospital for Sick Children
Neurofibromatosis type 1 (NF1) is one of the medical conditions reported among autistic
individuals at a surprisingly high frequency of about 6%. While the NF1 disease causing
gene was identified many years ago, so far, no convincing autism susceptibility genes are yet
known. There is now overwhelming evidence, however, that an autism gene resides on
human chromosome 17 near to where the NF1 gene is located.
What is Autism?
Autism is a brain disorder that affects a person’s ability to communicate, form relationships
with others, and respond appropriately to the environment, typically by 3 years of age. The
population prevalence is about 1 in 1000 with a four-fold higher incidence in boys than in
girls. Some people with autism are relatively high-functioning, with speech and intelligence
intact. Others are mute, or have serious language delays. For some, autism makes them
seem locked into repetitive behaviors in their child. In many cases their baby may seem
"different" from birth being unresponsive to people and toys, or focusing intently on one
item for long periods of time. The first signs of autism may also appear in children who
were developing normally. When an affectionate, babbling toddler suddenly becomes silent
or withdrawn, something is wrong.
Factors Affecting Brain Development
But what causes brain development to go awry? Some researchers are investigating genetic
causes-the role that heredity and genes play in passing the disorder from one generation to the
next. Autism does not appear to be caused by one particular gene. If autism, were passed
along by a single gene, more family members would inherit the disorder. Therefore, autism
is likely to be a complex genetic disease with many genes contributing. Our group and
others are searching for irregular segments of the DNA genetic code that the autistic member
of a family may have inherited. As mentioned earlier, a number of studies show that there is
an autism susceptibility gene on chromosome 17 in the same region as the NF1 gene. Our
team would like to see if we can find this gene by studying individuals that have both NF1
and autism inherited in the same family with the ultimate goal being to determine the cause
for the co-occurrence of these two disorders.
We have been collecting blood samples from individuals having NF1 and autism. There are
reports in the medical literature and our preliminary research has found many families in
Ontario and Canada where autism and NF1 are observed. To assist our research into autism
we are searching for more families having both of these conditions. Understanding exactly
how these conditions disrupt brain development may provide insights to the genetic and
biological mechanisms of autism allowing early diagnosis and perhaps treatment. Our
research is supported by many granting agencies including the Canadian Institutes of Health
Research. For more information or if you are interested in participating please contact Dr.
Stephen Scherer (steve@genet.sickkids.on.ca).
|
| ASSOCIATION OF BONY FEATURES IN
NEUROFIBROMATOSIS 1
– S. Alwan, L. Armstrong, J. M. Friedman, P.H. Birch, Dept. of
Medical Genetics
– H. Joe, Department of Statistics, University of British Columbia,
Vancouver, B.C.
– J. Szudek, Dalhousie Medical School, Halifax, Nova Scotia, Canada
T he most common sites of osseous (or bony) dysplasia that are characteristic of Neurofibromatosis 1
(NF1) involve the long bones (usually the tibia), vertebrae and sphenoid wing. Such lesions may cause
profound clinical consequences with often unsatisfactory treatment. People with NF1 are usually
shorter than expected for their age, gender and family. The pathogenesis of osseous dysplasia and its
relationship to short stature are yet to be determined. This study was performed to examine
associations between the occurrence of osseous lesions in 3377 NF1 probands retrieved from the
National NF Foundation International Database using logistic regression and probit models. While
adjusting for age and gender, our results gave significant outcomes for an association between the
occurrence of sphenoid wing dysplasia and dysplasia of the long bones and the vertebrae. A future
analysis was carried out to compare the height of individuals with NF1 and either vertebral or long bone
dysplasia to the heights of individuals with NF1 without known bony dyslpasias using 366 NF1 cases
from the National NF Foundation International Database. We found a significant relationship between
the height of people with NF1 and the presence of vertebral dysplasia. This may reflect concomitant
scoliosis that can affect stature. We conclude that some people with NF1 are more likely to develop
osseous dysplasia than others, and speculate that there may be a common pathogenetic mechanism
responsible for the development of sphenoid wing dysplasia and that of the vertebrae and the long
bones.
|
| A FATHER’S DEALINGS WITH NF
– By Jeff Woods
O n May 3rd, 1994 a miracle arrived, it was the
birth of our first child Brandon. He was
incredibly cute and had a great set of lungs, he
was perfect. When he was released from the
hospital I showed him off to everyone. The pride
involved in having a child after trying for so long
was amazing. He had great big brown eyes and
he would look at you in such a way as to make
your heart melt. At least that is how he made me
feel.
The day arrived to take him to his first
appointment with the doctor, our regular GP. At
the start of the examination she mentioned that
he had a couple of large freckles which she called
café au lait spots. I sat there thinking well isn’t
that nice he has freckles. She then said " these
spots usually indicate the presence of a disorder
called Neurofibromatosis." My son had a
disorder? This wasn’t possible cause he was
perfect. My heart stopped and it felt as if
someone had kicked me in the groin. After I
could think again, I asked the doctor what the
heck is Neurofibwhatis. She gave us a brief
breakdown of what the word meant: Neuro
means nerves and Fibro means a growth. So the
disorder caused tumors or fibroma to grow on the
nerves.
I came home from the appointment wanting to
scream, yell or even destroy something. The
pride that had been so strong had turned to
anger. How dare my son have a disorder! The
devastation was complete. I tried to talk to my
family but while there was pity, there was no
ability to help. Cancer, diabetes, or even leprosy
they could have understood and been able to deal
with but this was something that none of us had
ever heard about. The local doctors with the
exception of our GP knew nothing about this
disorder and if they did, they seemed reluctant to
give a diagnosis. We took my son to specialist by
the seemingly dozens and not one would get off
the fence and say yes, he has NF.
About a year and a half of trying to get a definite
answer to our questions, we ran into another
hurdle. The plexiform tumor on his back had
grown until he was unable to sit in his car seat
without pain. The doctors had previously refused
to remove it until "it is necessary". So at the age
of 2 1/2, Brandon went under the knife to have
the tumor removed from his back near the spine.
The wait was indescribable. After 2 hrs, the
doctor came to us and said that he was fine but
that she couldn’t remove all of it, it had grown
under the spine. So, we packed him up and took
him home. The next morning he was up and
ready to play, jumping on his bed and trying to
run around. I was amazed with his recovery.
While we were trying to deal with our son’s
problems, we forgot about dealing with our own.
My wife became tIred and seemed unwilling to
do anything around the house (the ultimate
couch potato). While I was working she would
sit at home doing nothing, or so I thought at the
time. As is very common with families with a
child diagnosed with a spontaneous mutation of a
disorder or disease, the parents, my wife and I
were slipping into a depression. My wife’s
apparent laziness was just one of the more
apparent signs, but I was too caught up in my
own downward spiral to feel anything but anger.
As I look back now, I realize that I was as bad if
not worse in shape than she was but could I say
anything, no way. I started to be bothered by
everything and anything, I was a walking time
bomb. My wife finally went to see our GP and
she got the help needed. The change while
gradual was amazing to behold. At this point I
realized that I had 2 choices, the first was to
continue down the path of anger and end up
destroying myself or try to pull myself out and in
doing so, help my wife and son. So, I too sought
help. What a difference it made to both my
married life and our ability to help our son.
The next big cliff we came to was when Brandon
started school. The teachers started complaining
about him hitting other kids and not being able
to pay attention or stay still. One time he was
playing Power Rangers and punched a boy in the
nose, when asked why he did it, the reply was I
didn’t realize I was doing it until it was done.
Once again we sought the consult of our GP and
she said that the symptoms sounded like
Attention Deficit Hyperactivity Disorder
(ADHD). He was started on Ritalin with our
hope that this was the answer. The years have
rolled by, his medications increased (twice a day to
2 pills twice a day) and changed from regular to
slow release and now to a new 12 hour brand.
As the years have rolled by, I’ve watched my son
grow from baby with a disorder to a young man
who would give his last dime to help someone he
doesn’t even know. While you can still see the
many fibroma on his neck and torso, it doesn’t
detract form the fact that my first opinion of my
son was right. He is perfect.
|
| MAY IS NF
AWARENESS MONTH!
ENJOY A CUP OF TEA.
|
| WOULD YOU LIKE TO SHARE YOUR STORY
WITH FELLOW NF MEMBERS?
We are always looking for articles and items for upcoming newsletters. If you
have had your local newspaper write a story about Neurofibromatosis or
considering it, please do it now. The month of May is an excellent time to
share your story, during NF Awareness Month. We can help you get started.
|
|
