Osteogenic Profiling of Tissue From Children With Craniosynostosis

The screening procedures include review and collection of information from the patient's
medical record, Name, Date of Birth, Medical record number, clinical diagnosis of
classification of craniosynostosis, genetic screen for syndromic synostosis (FGFR, TWIST,
MSX2 mutation screen), and a clinical examination at the Cleft -Craniofacial Center. During
the clinical examination, the plastic surgeon will determine the presence of a
craniosynostosis and the need for surgical intervention. The evaluation and surgical repair
of these patients with craniosynostosis will not differ from normal, nor from the current
standard of care.

In order to reconstruct, reshape, and expand the contours of the deformed craniofacial
skeleton, large skin incisions and subcutaneous dissections are necessary to allow for
sufficient exposure during the procedure. These large incisions and dissections are a
necessary part of the reconstruction. During the normal course of the procedure, temporalis
muscle, a muscle of mastication in the temporal area, and subcutaneous adipose will be
visible and exposed. It is only after the plastic surgeon has obtained this standard exposure
that excisional biopsies of a maximum size of 2mm X 2mm X 3mm will be taken from consented
patients. Bone samples will be collected from bone tissue that would normally be discarded
during the reconstructive surgery, so no additional procedures are needed to collect the bone
samples. Biopsy samples will not be provided to secondary investigators. The muscle and
adipose biopsies are research required procedures. At the time of surgery one sample of
tissue will be taken from temporalis muscle, subcutaneous adipose, and bone. The investigator
will review the results of the test/procedure that are part of the standard of care and
results will become part of the research record. The investigators will continue to use and
disclose identifiable medical information and keep stored tissue samples for seven years.
After this seven year period, all identifying information will be removed samples will be
destroyed.

The muscle and adipose tissue biopsies will take approximately 10 minutes. The samples of
bone tissue will be discarded as a result of the reconstructive surgery and will, therefore,
not add any time to the surgical procedure.

Subjects will not be notified of the results of this study because the results will not
impact the clinical care of the subject.

Inclusion Criteria:

- Children with craniosynostosis undergoing surgical calvarial reconstruction between
the ages of 2 months of age to 18 years old will be included in this study. This
surgery is the standard of care in the sequence of treatment for craniosynostosis
patients. Pediatric plastic surgeons at the Cleft-Craniofacial Center at Children's
Hospital of Pittsburgh of UPMC work primarily with children as part of their patient
populations and are trained for this during their residencies. Children will be
evaluated initially at the Pittsburgh Cleft Palate and Craniofacial Center at
Children's Hospital of Pittsburgh which is set up to accommodate children of all ages
and their families.

- Approximately twelve to twenty children are normally treated in this facility each
year.

- All patients will be asked to contribute to this study.

- The research study satisfies risk Criterion 3 (45 CFR 46.406) for the inclusion of
children in research whereas the research involves an intervention or procedure that
presents greater than minimal risk to the involved children and which does not hold
out the potential for direct individual benefit. Pediatric patients undergoing
surgical repair craniosynostosis normally do not have a biopsy of the temporalis
muscle or the adipose tissue of the scalp (experimental procedures). These biopsies
will be performed by a plastic surgeon who is experienced in the surgical repair of
pediatric patients and poses no additional likely or common risks above the surgical
repair of the calvaria. Infrequent risks may include a slight increase in bleeding
representing a few more drops of blood loss. Rare risks, occurring in less than one
percent of patients, may subject the patient to injury to nerves in a small area of
the biopsy which may result in a decrease of muscle function in that area. This
intervention could provide detailed, basic information regarding the relationship
between the progenitor cells and craniosynostosis.

Exclusion Criteria:

- All patients not undergoing calvarial reconstruction to correct craniosynostosis will
be excluded from this study.

- Selection will be based on an individual's willingness to participate in the study.

- A subject will also be removed from the research study if the targeted muscle,
adipose, or bone tissues are unavailable due to necrosis, infection, or if the removal
of the tissues may adversely effect the surgical outcome in some way.