Development of an international database of patients with holoprosencephaly and related brain malformation

Holoprosencephaly (HPE) is an early embryonic malformation sequence of the vertebrate forebrain that occurs both as an isolated anomaly and in multiple malformation syndromes. HPE is characterized by incomplete bifurcation of the forebrain into distinct left and right hemispheres, a process normally complete by the fifth week of gestation. It is the most common developmental defect of the forebrain and midface in humans occurring in 1 in 250 pregnancies; the live birth prevalence is only about 1 in 10,000. Although a large number of genetic causes of syndromic and nonsyndromic HPE have been identified, in addition to several well-known teratologic causes, the majority of cases of HPE remain genetically or biochemically unexplained.

The Carter Center for Brain Research in Holoprosencephaly (HPE) at Kennedy Krieger Institute has been in operation since February 1998. The purpose of this multi-center research is to create an International Database that contains information on as many children as possible with Holoprosencephaly (HPE). It is a collaboration and data-sharing effort between:
-The four Carter Centers for Brain Research in Holoprosencephaly: Kennedy Krieger Institute, Texas Scottish Rite Hospital for Children, the Lucile Salter Packard Children’s Hospital at Stanford University and the Rutgers State University of New Jersey.
-Dr. Max Muenke and his team at the National Human Genome Research Institute in Bethesda, Maryland.

This study involves a medical record review of child’s past medical records, parent interview to record prenatal and pertinent family history and demographics, confirmation of diagnosis via neuroimaging brain scan review and, if possible, clinical evaluation at one of the Carter Centers. Data collected from medical record review and initial and follow-up clinical examinations, as well as photographs, blood test results and brain scans, are shared with the other Holoprosencephaly research centers and entered into an International HPE Database to be used for research purposes only. Patients are referred by physicians, self-recruited from the Carter Center website at: www.stanford.edu/group/hpe or recruited from outpatient clinics and/or less frequently from inpatient hospitalizations (KKI/JHH).

Inclusion criteria includes children with Holoprosencephaly or a related brain malformation aged birth to 18 years; children in foster care are excluded. There is no direct medical benefit to study participants. By collecting information on children with HPE from all over the world, we do hope to learn more about HPE; this may lead to new knowledge which will improve the future care of children with HPE. Participation in the International HPE Database poses minimal risk to the child and the parents. The clinical evaluation may necessitate the child missing one to three days of school and the parent(s) missing work. As with other doctor visits, the clinical evaluation may cause minor stress and fatigue for the child. It may also be stressful for the parents. Child participants will be given rests during the clinical exam to avoid becoming tired. To minimize the risk to confidentiality, the child’s name will be kept confidential and will be deleted from all information that is used for research purposes. The way in which we collect information will be reviewed often to make sure that confidentiality is maintained.