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