craniosynostosis is a wonderfully descriptive term , meaning " the skull has fused bone " . however , it is also a fairly nonspecific clinical designation , encompassing multiple presentations ranging from isolated single suture involvement to multi - sutural fusions5 ) .
multi - sutural fusion can occur as isolated fusions or with associated anomalies that occur outside the skull .
epidemiologic studies have suggested that the incidence of craniosynostosis may be as high as 1 in 1700 live births612 ) .
for example , early theories regarding the pathogenesis of this condition , based on clinical observations and an experimental animal model , included intrauterine constraint811 ) . over the last quarter century , there have been many advances in the understanding of craniosynostosis , resulting in more rational management of the problems associated with this condition , both in its simple form and its syndromic manifestations315 ) .
these advances have included reduced emphasis on the technical aspects of this disease and greater emphasis on its pathology and natural history , along with more accurate analysis of the morphology of the craniofacial skeleton1310 ) .
more recently , genetic studies have identified the genetic loci of many craniosynostosis syndromes , as well has determining the downstream pathways associated with disease development .
recent clinical and genetic studies have identified multiple forms of human craniosynostosis , each associated with mutations within various growth factor signaling pathways .
knowledge gathered from these investigations may result in the future development of alternative strategies to enhance or perhaps even replace current approaches for the treatment of craniosynostosis .
craniosynostosis was first treated surgically in the late 1800s , using techniques such as fragmentation of the cranial vault and linear craniectomies .
these early procedures were associated with high rates of reossification and poor esthetic outcomes , mandating many subsequent procedures7 ) . at present , however , simple craniectomy is used only in patients with transient cranial decompression .
these early procedures have been supplanted by surgical remodeling of the affected area of the cranial vault and orbits .
surgery is generally performed at age 69 months to take full advantage of the regenerative capacity of the skull at this age .
three stages of growth have determined the approach to the management of craniosynostosis3 ) . during this time , cerebral growth is the greatest , and craniosynostosis may have detrimental effects on the developing brain . the original surgical approach consisted of excision of the premature suture or sutures by linear craniectomy , allowing the growing brain to expand .
if urgent decompression was required , fronto - orbital advancement and multiple suture excisions were performed , resulting in lateral and posterior expansion .
after the second year , cerebral growth slows ; nevertheless , severe craniostenosis may still lead to papilledema and potential visual failure .
the cranial capacity must therefore be expanded by large bilateral decompressive craniotomies , generous fronto - orbital advancement , or a combination of these procedures .
definitive facial surgery can be performed , beginning at age 10 years , although waiting until maturity may achieve better esthetic outcomes .
patients with crouzon syndrome who have proptosis and/or maxillary hypoplasia are especially likely to need surgical treatment1214 ) .
early surgical correction has been limited by a late diagnosis and the risks associated with intraoperative blood loss , which was less effectively managed in the past than currently13 ) . since the beginning of the 21st century
, many centers have tended to determine whether a less invasive procedure could be performed at an earlier stage with acceptable risk .
endoscopic linear craniectomy , with postoperative application of helmets and cranial remodeling through small skin incisions , has led to cosmetic results comparable to those of more invasive procedures if performed during the first 46 months of life , with acceptable blood loss and operative risks13 ) .
more recently , the combination of frontal advancement and posterior cranial enlargement during the first months of life has been found to protect both the ocular and posterior cranial structures .
currently , a free bone flap ( floating technique ) or springs are used to allow for cerebral growth until a rigid fronto - orbito - maxillary advancement can be performed13 ) .
the advent of osteodistraction has lowered the age for facio - maxillary advancement ( 35 years ) , and may avoid the necessity of repeating fronto - orbital procedures .
this has reduced the risks of dural tears and postoperative cerebrospinal fluid fistulas in a significant proportion of patients . as the procedures used to remodel the calvarial vault are extensive
although the mortality rate has been reported to be as high as 2.3% , most international studies had mortality rates of 1.5% to 2%7 ) .
most deaths were attributed to hemorrhagic complications , but various other causes have been reported , including air emboli , cerebral edema , and respiratory infections4 ) .
attention to intraoperative hemodynamics and careful postoperative intensive care unit monitoring are critical in minimizing overall morbidity and mortality rates .
during this time , cerebral growth is the greatest , and craniosynostosis may have detrimental effects on the developing brain . the original surgical approach consisted of excision of the premature suture or sutures by linear craniectomy , allowing the growing brain to expand .
if urgent decompression was required , fronto - orbital advancement and multiple suture excisions were performed , resulting in lateral and posterior expansion .
after the second year , cerebral growth slows ; nevertheless , severe craniostenosis may still lead to papilledema and potential visual failure .
the cranial capacity must therefore be expanded by large bilateral decompressive craniotomies , generous fronto - orbital advancement , or a combination of these procedures .
definitive facial surgery can be performed , beginning at age 10 years , although waiting until maturity may achieve better esthetic outcomes .
patients with crouzon syndrome who have proptosis and/or maxillary hypoplasia are especially likely to need surgical treatment1214 ) .
early surgical correction has been limited by a late diagnosis and the risks associated with intraoperative blood loss , which was less effectively managed in the past than currently13 ) . since the beginning of the 21st century , many centers have tended to determine whether a less invasive procedure could be performed at an earlier stage with acceptable risk .
endoscopic linear craniectomy , with postoperative application of helmets and cranial remodeling through small skin incisions , has led to cosmetic results comparable to those of more invasive procedures if performed during the first 46 months of life , with acceptable blood loss and operative risks13 ) .
more recently , the combination of frontal advancement and posterior cranial enlargement during the first months of life has been found to protect both the ocular and posterior cranial structures .
currently , a free bone flap ( floating technique ) or springs are used to allow for cerebral growth until a rigid fronto - orbito - maxillary advancement can be performed13 ) .
the advent of osteodistraction has lowered the age for facio - maxillary advancement ( 35 years ) , and may avoid the necessity of repeating fronto - orbital procedures .
this has reduced the risks of dural tears and postoperative cerebrospinal fluid fistulas in a significant proportion of patients . as the procedures used to remodel the calvarial vault are extensive
, complications can occur following surgery for craniosynostosis . although the mortality rate has been reported to be as high as 2.3% , most international studies had mortality rates of 1.5% to 2%7 ) .
most deaths were attributed to hemorrhagic complications , but various other causes have been reported , including air emboli , cerebral edema , and respiratory infections4 ) .
attention to intraoperative hemodynamics and careful postoperative intensive care unit monitoring are critical in minimizing overall morbidity and mortality rates .
the combination of early technical success with recent advances in treatment14 ) has indicated the necessity of multidisciplinary management .
the overall approach can be distilled into six principles9 ) : 1 ) care should be provided by multi - disciplinary teams ; 2 ) care should be a protocol - driven process , with all forms of care defined and delivered optimally ; 3 ) care should be longitudinal , as age , healing and growth processes ; 4 ) secure financial support is needed to implement such longitudinal care11 ) ; 5 ) competent professionals should be involved in ongoing education and training in teaching and research ; and 6 ) research should explore causes , treatment strategies , and treatment outcomes .
centers with the appropriate vision and infrastructure are necessary to optimize the care of patients with craniosynostosis , as well as to enhance scientific knowledge and education about this disease .
several investigations have evaluated the roles of various growth factors and cytokines in determining the fate of sutures .
fibroblast growth factors ( fgfs ) are particularly important , as mutations in their receptors have been implicated in many craniosynostosis syndromes .
mutations in three of the four known fgf receptors have been associated with premature pathologic suture fusions1617 ) .
recent advances in developmental biology and genetics have identified some of the events governing suture fate , highlighting multiple axes of cellular signaling with the potential for clinical manipulation . such knowledge and comprehension
may facilitate therapeutic translations , ultimately enhancing or perhaps even replacing contemporary modalities for treating craniosynostosis .
 craniosynostosis has a varied clinical spectrum , ranging from isolated single suture involvement to multi - sutural fusions . 
 greater understanding of the pathogenesis of craniosynostosis has led to the development of practical treatment protocols . 
 three stages of growth have determined the approach to managing craniosynostosis : the early period , up to 12 months ; the intermediate period , from 1 to 10 years ; and the late period , beginning at 10 years . 
 this review discusses current surgical management and future perspectives in craniosynostosis . 