Genetic Analysis of Craniosynostosis, Philadelphia Type
Genetic Analysis of Craniosynostosis, Philadelphia Type
This study will try to find the gene changes responsible for the birth defects in
 craniosynostosis, Philadelphia type. Craniosynostosis syndromes are a group of conditions
 that result from closure of one or more of the fibrous joints between the bones of the skull
 before brain growth is complete. Because of the premature closure, the brain is not able to
 grow in its natural shape; instead, it compensates with growth in areas of the skull where
 the joints have not yet closed. The defects in raniosynostosis, Philadelphia type, include
 skull malformations and webbing of the fingers and toes. Gene changes known to be involved in
 other craniosynostosis syndromes have not been found in the Philadelphia type syndrome.
 Therefore, finding the genetic basis of this disorder will provide important new information
 regarding craniofacial and limb development.

 This study includes members of a single large family affected with craniosynostosis,
 Philadelphia type.

 Participants have 1 to 2 teaspoons of blood drawn for genetic studies. A second blood sample
 may be requested for further research. Some blood may be used to establish a cell line for
 later studies. This involves growing the white blood cells from the blood sample. The cells
 can be kept in the laboratory to make more DNA or can be frozen for later use in
 craniosynostosis studies. Patients may also have their medical records reviewed.
The objective of this study is to determine the molecular basis of craniosynostosis,
 Philadelphia type. Previous studies by our lab have excluded FGFR1, FGFR2 and FGFR3, the
 causative genes of most hereditary craniosynostosis syndromes. In the five generation kindred
 previously reported we have conducted a genome-wide linkage analysis. We have identified four
 regions linked to this disorder, namely on 2q, 12q, 20q and 22q. Interestingly, syndactyly
 1A, a phenotypically similar disorder, demonstrates an overlapping linkage region in two
 studies. Screening of candidate genes in the redion has excluded ten candidate genes,
 including IHH, IGFBP2 and IGFBP5.

 This protocol is primarily for research purposes. Research subjects may receive benefit from
 knowing that this research may help other families in the future. Results will be discussed
 with the primary physician who is a trained medical geneticist. We will emphasize that these
 are only preliminary findings, that they are not CLIA-approved, and must not be disclosed to
 the patient or included in the medical record. Repeat testing in a CLIA-approved lab would be
 required before the specific genetic information could be shared with the patient and family.
-  INCLUSION CRITERIA:

 This research includes only craniosynostosis Philadelphia type patients and members of a
 single family who were previously referred to us and other family members who have since
 displayed interest in participating in this study.

 EXCLUSION CRITERIA:

 Anyone unwilling to provide informed consent (for themselves as adults, or on behalf of
 their children as minors) or assent.

 Medical condition(s) are not in themselves reason for exclusion if in the judgment of the
 referring physician this would involve no more than minimal risk.

 We generally reviewed a brief clinical description from the referring physician about a
 potential research subject to determine that the subject was appropriate to enter into the
 study. We reserved the right to exclude cases that were clearly not related to our direct
 research interests. For new participants, we will review the clinical description from the
 referring physician and we reserve the right to exclude cases.