Clinical and Genetic Studies on Holoprosencephaly

Study start date: January 23, 2004

* INCLUSION CRITERIA: 1. Depending on their willingness to participate, subjects may enroll in DNA laboratory-only (98-HG-0249), psychosocial-only, or clinical-only. However, to conserve resources and meet study objectives, subjects with known mutations will be given priority in selection for extensive clinical studies. All races and genders are known to be at risk for HPE, anywhere in the world. Nationality or place of origin is not specific barrier to participation. 2. Direct blood relatives (typically parents, and occasionally siblings of affected individuals) of patients with HPE are also eligible to participate. EXCLUSION CRITERIA: 1. Anyone unwilling to provide informed consent (for themselves as adults, or on behalf of their children as minors) or assent. 2. Medical condition(s) or mental retardation are not in themselves reason for exclusion if in the judgment of the referring physician this would involve no more than minimal risk. We anticipate that children with mental handicaps would be included in the research population. We will make every effort to explain the study for the purpose of assent in a manner that the family feels is both age and developmentally appropriate for that child. 3. We generally review a brief clinical description from the referring physician about a potential research subject to determine that the subject is appropriate to enter into the study. We reserve the right to exclude cases that are clearly not HPE or related to our direct research interests (e.g. HPE cases that are syndromic like Smith Lemli Opitz syndrome, Trisomy 13, Trisomy 18, drug-related, or teratogen-related). This almost never happens, and we would attempt to make referrals to a more appropriate investigator. It is our intention to try to remove as many economic, cultural, geographic, racial, and gender barriers as we reasonably can to promote participation of HPE cases for research purposes. Description and justification of clinical inclusion/exclusion criteria for environmental study arm control group (individuals with Williams syndrome) : Participants must have a confirmed diagnosis of Williams syndrome caused by deletions in chromosome 7q11 involving the Williams-Beuren Syndrome Critical Region (WBSCR). Children should be less than 6 years of age to allow for improved maternal recall of prenatal environmental exposures. The Williams syndrome cohort (PI: Dr. Beth Kozel; National Heart Lung Blood Institute) was chosen to allow for inherent biases in mothers who have children with multiple anomaly syndromes.