Research intensifies with
changing attitudes about rare brain deformity
BY MITCH LESLIE
Just a few years ago,
children born with the brain deformity holoprosencephaly
were usually written off as hopeless. Because the front
of the brain doesn't grow properly and fails to cleave
into two hemispheres, most doctors reasoned that the
children faced a bleak and probably short life.
But if you visited the
pediatric neurology department at Lucile Packard
Children's Hospital today, you might meet one of the 15
children with HPE the hospital is monitoring and treating
as part of a national effort to better understand this
mysterious disorder.
Two years ago the hospital
became one of the Carter Centers for Brain Research in
Holoprosencephaly and Related Malformations, a consortium
of five universities and hospitals dedicated to HPE
research and treatment. Funding for the Carter Centers
comes from the Don and Linda Carter Foundation and the
Carter Chancellor Urschel Neurobiology Research Fund. Don
and Linda Carter's grandson has a mild form of the
disorder.
Reflecting this change in
outlook, the National Institutes of Health early this
month sponsored a two-day conference on HPE in Bethesda,
Md., the first national scientific meeting dedicated to
this disorder. Along with scientific sessions, the
conference also included a daylong meeting where parents
of children with HPE could learn about the latest news in
treatment and research.
These developments stem
from a revolution in attitude rather than a breakthrough
in treatment. "We like to focus on the positive
aspects of these children, what they can do rather than
what they can't do," said Vicki Sweet, RN, Carter
Center Director.
According to Jin Hahn, MD,
associate professor of neurology and neurological science
and medical director of the Carter Center at Stanford,
the different Carter Center sites have divided up the
work of understanding this disease. Packard Hospital is
one of three clinical centers treating patients with HPE
and collecting information on their symptoms and
progress. The other two clinical sites are Kennedy
Kreiger Institute in Baltimore, Md., and Texas Scottish
Rite Hospital for Children in Dallas. Researchers at
Rutgers University are developing tests to assess the
cognitive abilities of children with HPE, while
scientists at Children's Hospital of Philadelphia are
investigating the genetics of the disorder.
Scientists hope that the
increased attention may help answer some fundamental
questions about HPE, Hahn said. For example, no one knows
how common the disorder is, although a rough estimate is
1 in 5,000 to 1 in 10,000 births. The defect appears
about four to six weeks into pregnancy when, for reasons
that are not well understood, brain growth goes awry.
Often, HPE causes a miscarriage, and the disorder may lie
behind as many as 1 in 200 miscarriages. Scientists also
know little about the long-term course of the disease,
such as how long patients can expect to live and how the
symptoms change over time.
The cause of HPE also
remains elusive, Hahn said. Genes are clearly responsible
for some cases, and in one family the disease was traced
to a defect in the Sonic Hedgehog gene, a regulator of
development that has widespread effects. Other cases are
related to chromosome damage, but no common, underlying
genetic cause has been discovered, Hahn said. For unknown
reasons, HPE appears to be slightly more common among
Hispanics, particularly in families from Mexico.
HPE's severity ranges from
barely noticeable to disabling, said Sweet. Children with
the mild form often have few if any symptoms and can
attend school. They may also have a normal life span,
though few studies have investigated longevity of HPE
patients. More severely affected children often have
hormone imbalances because of defects in the pituitary
gland. Many of them are mentally impaired and have
difficulty walking because of abnormal posture and muscle
tone. Facial deformities such as cleft lip, cleft palate
and missing teeth are common as well. No treatments can
repair the brain abnormalities, and severely affected
children generally need supportive care to survive, Hahn
said.
One of the goals for
Stanford's portion of the research is performing
comprehensive evaluations on all children to better
understand the range of symptoms. Stanford's researchers
are also cooperating with doctors at the University of
California, San Francisco, to perform imaging studies
aimed at classifying the possible brain abnormalities.
Another goal is to get a clearer picture of how the
disease affects longevity and mental development by
tracking the children for many years. "We want to
find out the long-term outlook for all kinds of kids,
what they can achieve in development and cognitive
growth," said Hahn.
All of the data collected
by the different sites goes to a central archive in
Dallas, where other researchers can access it.
Parents who have children
with HPE can obtain more information by calling Vicki
Sweet at (650) 498-2692. The Carter Center also has a
website at http://www.stanford.edu/group/hpe. SR
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