Grants We Funded

Abstract
Craniosynostosis (CS) is defined as the premature closure of one or more cranial sutures. CS leads to an abnormally shaped head and can cause cognitive and neurologic deficiencies. Treatment requires surgical removal of the fused suture to expand the cranium and to create space for the brain to grow. However, a major complication is rapid re-ossification of the surgical site – that is, post-suturectomy re-ossification (PSRO). Once the suturectomy site re-ossifies, the cranium is again restricted and the patient is again faced with the same dangers of CS that were present prior to surgery. PSRO can lead to restriction of craniofacial growth, intracranial hypertension, and ultimately require re-operation.

PSRO is poorly understood and the pathological process whereby it occurs is unknown. Thus far, only clinical observations exist to suggest that young age and the presence of a syndrome may impact the development of PSRO. In the context of these observations, it is logical to think that PSRO is influenced by: 1) the increased osteogenic potential observed in young animals and humans, and 2) the underlying disease process that lead to suture fusion initially.

The goal of this proposal is to investigate the impact of young age on PSRO in a mouse model of Saethre-Chotzen syndrome. To accomplish this goal, mice with the Twist+/- mutation (a model for Saethre-Chotzen syndrome) will undergo coronal suturectomy (surgical excision of the coronal sutures) at two different ages. One group will be infant mice and the other adolescent mice. This will result in four groups: 1) infant normal mice, 2) infant Twist+/- mice, 3) adolescent normal mice, and 4) adolescent Twist+/- mice. PSRO will be evaluated based on bone regeneration within the suturectomy site measured at 1, 2, 4 and 8 weeks by CT imaging and histology.

This work is important because the pathophysiology of PSRO is unknown and preventative strategies do not exist. We need to measure the relative impact of age and syndromic status to help define the parameters that control the onset of PSRO. To date, no studies have investigated how young age affects post-suturectomy re-ossification of a pathologically fused cranial suture.

Completion of this study may provide valuable insight into the influence of young age and the Twist+/- mutation on the development of PSRO and may provide therapeutic targets to prevent complications and improve overall outcomes for patients with CS.

Biography
A child’s skull is composed of multiple bony plates separated by narrow fibrous structures that join the bony plates. Craniosynostosis is a disease characterized by bone prematurely fusing across these fibrous structures. The child is stricken with an abnormally shaped head and cognitive and neurologic deficiencies. Treatment requires surgical expansion of the skull. However, a major complication is rapid bone growth into the surgical site, which stunts craniofacial growth, requiring additional surgeries. The cause of this complication is unknown. By identifying risk factors, we will provide a therapeutic target to prevent complications, improve craniofacial growth, reduce the number of surgeries children undergo, and achieve overall better outcomes for children with craniosynostosis.