MOC-CME

Evidence-Based Medicine: Craniosynostosis

Jeffrey A. Fearon, M.D.
Dallas, Texas

Learning Objectives: After studying this article, the participant should be able
to: 1. Make the appropriate diagnosis for each of the single-sutural synostoses,
based on the physical examination. 2. Explain the functional concerns associated with these synostoses and why surgical correction is indicated. 3. Distinguish
between the different types of surgical corrections available, the timing for
these various interventions, and in what ways these treatments achieve overall
management objectives. 4. Identify the basic goals involved in caring for the
syndromic synostoses.
Summary: This article provides an overview of the diagnosis and management of infants with craniosynostosis. This review also incorporates some
of the treatment philosophies followed at The Craniofacial Center in Dallas, but is not intended to be an exhaustive treatise on the subject. It is
designed to serve as a reference point for further in-depth study by review
of the reference articles presented. This information base is then used for
self-assessment and benchmarking in parts of the Maintenance of Certification process of the American Board of Plastic Surgery. (Plast. Reconstr. Surg.
133: 1261, 2014.)

DESCRIPTION, INCIDENCE, AND

PATHOGENESIS
Craniosynostosis is a wonderfully descriptive
term: the skull has fused bones. However, it is
also a fairly nonspecific designation, encompassing multiple different presentations ranging from
isolated single-sutural involvement to multisutural fusions. The multisutural fusions can occur
either as isolated fusions (complex craniosynostoses) or with associated anomalies occurring outside of the skull (syndromic craniosynostoses).
Epidemiologic studies suggest that craniosynostosis occurs with an incidence as high as one in
1700 live births.13 A number of different causes
for craniosynostosis have been proposed.4 Early
theories for the pathogenesis of this condition
included intrauterine constraint, based on both
clinical observations (noted in twins and in a
mother with a bicornuate uterus) and an experimental animal model (glue fixation in 9-day-old
rabbits).57 Koskinen-Moffett etal. added further support to the intrauterine constraint theory using a murine model that revealed sutural
fusions following prolongation of intrauterine
gestation.8,9 Although subsequent animal models
From The Craniofacial Center.
Received for publication February 26, 2012; accepted July
30, 2012.
Copyright 2014 by the American Society of Plastic Surgeons
DOI: 10.1097/PRS.0000000000000093

have presented contradictory evidence in support of this hypothesis, it appears that studies that
used animal models based on a prolongation of
gestation are more likely to show sutural fusions
than those that used exogenously applied plates
or glues, perhaps because, as Cohen has opined,
Growth restriction is not the same as growth
constraint.1015 Observational studies have also
linked valproic acid to the development of craniosynostosis (i.e., trigonocephaly).1618 Certain
metabolic conditions have been connected to
craniosynostosis (i.e., hypophosphatemic rickets).19,20 Craniosynostosis has also been observed
in association with excessive antacid use in infants
for the treatment of colic.21 Finally, observational
studies have linked maternal cigarette smoking,
thyroid disease, and the dietary intake of certain
nutrients to an increased risk for craniosynostosis
Disclosure: The author has no financial interest to
declare in relation to the content of this article.

Supplemental digital content is available for

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Plastic and Reconstructive Surgery May 2014

(although none of these studies has proven causation).2224 In addition to the aforementioned
environmental factors, anomalous sutural fusions
have been more commonly shown to arise secondary to numerous genetic mutations. Currently,
the most frequently identified mutations are associated with the syndromic synostoses including
the fibroblastic growth factor receptor (FGFR)
and TWIST genes (the vast majority of which
present with autosomal dominant inheritance
patterns).25,26 The complex craniosynostoses are
less commonly associated with gene mutations
(28 percent in one observational study), and the
single-sutural synostoses have up to fairly recently
been even more rarely associated with a specific
mutation.27 It is recognized that the recurrence
risk for single-sutural synostoses is higher (2 to
5 percent) for subsequent pregnancies (suggesting the role of helper genes), and a microarray
analysis of children with craniosynostosis has
identified candidates for c raniosynostosis-causing
mutations.28,29 An increased concordance rate
for craniosynostosis among monozygotic compared with dizygotic twins has also been noted,
implicating a genetic role for this condition, and
mutations for both isolated sagittal (BBS9) and
metopic (FREM1) synostoses have recently been
identified.3032 Craniosynostosis has also been
noted to occur more frequently in boys than in
girls, and androgen receptors have been found
in the murine fetal craniofacial skeleton, suggesting a role for testosterone in the development of
craniosynostosis.33

DIAGNOSIS
The diagnosis of craniosynostosis is typically
made on the basis of some type of radiologic
examination. Most often, after an anomalous
skull shape is first identified, the pediatrician
orders a diagnostic plain skull radiographic
series. When this proves suspicious for sutural
fusion, computed tomographic imaging is recommended for further clarification. Computed
tomographic imaging is currently considered the
criterion standard for diagnosing craniosynostosis. The accuracy of this diagnostic tool has been
demonstrated in a study of blinded observers
who ranked three-dimensional computed tomographic images as being better for diagnosing
craniosynostosis than standard computed tomographic images and plain radiographs.34 One cited
alternative to computed tomographic imaging for
detecting sutural fusion is the use of ultrasound;
however, the reliability of this technique among

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various users and among patients with different

ages has yet to be determined.35,36 Although it has
been standard process for craniofacial surgeons
to order confirmatory computed tomographic
scan imaging, a prospective multicenter study has
confirmed the high accuracy of diagnosis based
solely on a physical examination (98 percent),
even among surgeons of varying experience levels (Level of Evidence: Diagnostic, I).37 In light of
the accuracy of the physical examination and the
concerns that others have raised about the potential effects of radiation in children, including
developmental delays and increased incidence
for neoplasia (central nervous system and leukemia), our center has moved away from obtaining
routine computed tomographic scans in children
with craniosynostosis.38,39 When we are unsure of
the diagnosis, we will often see the infant back
for reexamination 4 months later to ascertain
how the skull has grown in the interim. However,
it is important to balance concerns associated
with exposure of the developing brain to radiation with the importance of securing the correct
diagnosis; therefore, surgeons should consider
reserving computed tomographic scans for those
rare instances when infants present with unsure
diagnoses and, when needed, ensuring that the
lowest possible radiation dose is used at the time
of scanning.
Considering that the diagnosis of craniosynostosis can usually be made solely on the basis of a
physical examination, what are some of the more
reliable diagnostic pearls? The first is that the presence of a palpable ridge running along a cranial
suture is not always pathognomonic for craniosynostosis. Early in life, sutures can appear to be
ridged (especially the coronal sutures) and later
flatten out as the skull grows. Moreover, lambdoid
synostosis often presents without any palpable
ridging. Instead of looking for sutural ridging, the
best diagnostic tool is having an overall appreciation for the changes in skull shape that accompany
each of the different sutural fusions. Knowledge of
the unique patterns of growth inhibition, and the
compensatory overgrowths, provides the astute
clinician the ability to accurately diagnose each
of the single-sutural craniosynostoses. The perturbation in skull shape resulting from craniosynostosis is commonly described as reduced growth
occurring perpendicular to the fused suture. In
actuality, the resultant growth inhibition is more
multidimensional (i.e., radial). In response to the
localized growth inhibition caused by a sutural
fusion, the remaining open sutures compensate, resulting in overgrowths occurring outside

Volume 133, Number 5 Craniosynostosis

Video 1. Supplemental Digital Content 1, in which Dr. Fearon

addresses how to diagnose single-sutural craniosynostosis, is available in the Related Videos section of the full-text article on PRSJournal.com or, for Ovid users, at http://links.lww.com/PRS/A988.

of the area of fusion. The following (in order of

frequency of presentation) is a brief description
of each of the four major single-sutural synostosis phenotypes. (See Video, Supplemental Digital
Content 1, in which Dr. Fearon addresses how to
diagnose single-sutural craniosynostosis, available
in the Related Videos section of the full-text
article on PRSJournal.com or, for Ovid users, at
http://links.lww.com/PRS/A988.)
Sagittal
One of the best examples of how sutural
fusion may result in a multidimensional pattern of
growth inhibition can be seen with sagittal synostosis, where in addition to a reduction in posterior

skull width, there is also a significant reduction

in posterior skull height (Fig.1). As a result of
this locoregional inhibition in growth, compensatory sutural growth occurs both posteriorly at the
lambdoid sutures (resulting in posterior dolichocephaly) and anteriorly involving the coronal and
metopic sutures (resulting in frontal bossing).
One of the markers of sagittal synostosis is the
development of an increased head circumference,
typically around the ninety-eighth percentile. This
increased head circumference is not representative of a larger brain, but instead is a reflection
of the anomalous compensatory growth occurring
anteroposteriorly, in response to the diminished
posterior skull height.

Fig. 1. In sagittal craniosynostosis, the birds-eye view (left) reveals posterior skull narrowing with compensatory elongation of the skull. Some frontal bossing can also be appreciated. The lateral view (right) is notable for an anterior shift in the highest point of the
skull, which occurs secondary to the characteristic reduction in posterior skull height.

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Conclusion
The posterior skull is narrowed and the height
is reduced, the skull is longer, and the forehead
shows variable bossing.
Metopic
Anomalous fusion of the metopic suture
results in a reduction in bifrontal width (Fig.2).
As a result of the impaired growth in the width
of the forehead, the sagittal and lambdoid sutures
compensate, resulting in an increased posterior
width of the skull, which further accentuates the
overall triangular appearance of the skull. Often,
there are varying degrees of hypotelorism, presumed secondary to midline constraint from the
metopic fusion.40
Conclusion
The forehead becomes progressively narrowed anteriorly and the skull compensates by
getting wider posteriorly, resulting in a triangular
appearance when viewed from above.
Coronal
With fusion of either one of the two coronal
sutures, reduced growth leads not only to unilateral forehead flattening, but also to elevation of
the ipsilateral superior orbital rim (Fig.3). As a
result of the diminished growth on one side of the
forehead, the other coronal suture compensates,
resulting in contralateral frontal bossing (both

forward and upward). These contradictory growth

patterns result in a shift of the frontal angle,
with deviation of the root of the nose toward the
affected side. When viewed from directly overhead, one can sometimes appreciate the overall
reduction in anteroposterior skull length on the
affected side.
Conclusion
The affected forehead is flatter, the ipsilateral eyebrow (supraorbit) is higher, and the nasal
radix angles toward the affected side.
Lambdoid
Closure of one of the lambdoid sutures results
in not only posterior skull flatness but also an ipsilateral reduction in posterior skull height (Fig.4).
Typically, a low mastoid bulge can be seen on the
affected side. The opposite lambdoid and sagittal
sutures compensate for the diminished growth,
resulting in contralateral posterolateral bossing. It
is important to differentiate lambdoid synostosis
from the much more commonly encountered posterior positional plagiocephaly. With positional
plagiocephaly, there is no reduction in posterior
skull height and no contralateral lateral parietal
bossing. It has been suggested that one helpful
diagnostic clue is the position of the ear canals.
Specifically, when the ear canal is shifted forward
on the same side as the posterior skull flatness,
the cause is deformational (i.e., positional plagiocephaly); however, when the ear is pulled posteriorly, lambdoid synostosis is the cause. As it turns
out, clinical series have shown that the position of
the ear canals is not a reliable diagnostic tool for
separating the two conditions.41,42 This is probably
because these two conditions may coexist.
Conclusion
In lambdoid synostosis, there is ipsilateral
posterior skull flatness, an ipsilateral reduction
in skull height, and contralateral parietal bossing,
which distorts the skull laterally.

Fig. 2. Trigonocephaly, the result of premature closure of the

metopic suture, produces a classic triangular skull shape. Isolated metopic ridging, without a trigonocephalic appearance,
does not require surgical intervention.

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Bicoronal
Although the single-sutural synostoses are by
far the most commonly encountered presentation
for craniosynostosis, some children may rarely
present with multisutural fusions. Of these, the
most common pattern of fusion includes both coronal sutures (which can occur as either isolated
closures or as part of a syndrome). As a result of
both coronal sutures fusing shut, the associated
growth impairments and compensations are symmetric, which may make an early diagnosis more
challenging. The following is a brief description

Volume 133, Number 5 Craniosynostosis

Fig. 3. With unilateral craniosynostosis, the modified birds-eye view (left) reveals frontal recession
on the right affected side, with compensatory left frontal bossing. These contrasting growth patterns result in a change in the angle of the frontal plane. The frontal view (right) reveals elevation
of the right supraorbit, with gentle deviation of the nose to the patients right, affected side.

of the phenotypic changes that commonly result

from bicoronal craniosynostosis.
Anomalous fusion of both coronal sutures
results in a symmetric flattening of the entire forehead with elevation of both brows (supraorbits).
As a result of the reduced frontal growth, there
is usually compensatory widening in the temporal

regions and increased skull height (turricephaly).

Often, the earliest sign of a bicoronal synostosis is
orbital proptosis, with both eyes appearing more
prominent. For both unicoronal and bicoronal
synostosis, FGFR testing is advisable to evaluate
for possible Muenke craniosynostosis. Of patients
with isolated unilateral coronal synostosis, it has

Fig. 4. Differentiating lambdoid craniosynostosis from positional plagiocephaly can be challenging. Left posterior skull flattening is noted in this patient (left), and although there is no corresponding frontal protrusion noted in this birds-eye view to suggest positional plagiocephaly, this
characteristic is not entirely diagnostic for synostosis. However, the presence of contralateral parietal compensatory overgrowth is highly suggestive of craniosynostosis. The posterior view (right)
shows a reduced ipsilateral skull height, with the presence of a characteristic low mastoid bulge.

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been reported that somewhere between 11 and 17
percent of affected children may test positive for
this mutation.43,44

SURGICAL INDICATIONS
Surgical correction for craniosynostosis is recommended for two reasons: (1) to correct the
abnormal appearance caused by the altered patterns of growth; and (2) to treat negative effects
on development, which could result from a
regional impairment of cerebral blood flow, arising from increased intracranial pressure, caused
by localized inhibitions in skull growth. Children
with craniosynostosis develop skull shapes that can
vary significantly from normal. Parents, and children as they get older, often desire a restoration
of normal appearance as the deformity becomes
increasingly noticeable, causing negative impacts
on social interactions. Although numerous studies have used intracranial pressure measurements
in support of surgical intervention, it is currently
unknown how high intracranial pressure must
reach, or for what duration, before development
is irreversibly adversely impacted (Reference 45
Level of Evidence: Diagnostic, IV).4549 A few published studies have specifically examined cerebral
blood flow in children with craniosynostosis, and
these have all demonstrated a reduction in blood
flow that is improved following surgical correction.5053 In spite of these few compelling observations, studies examining development provide
less clear indications for surgery (Reference 56
Level of Evidence: Risk, II).5457
Although the term craniosynostosis is ubiquitously used to signify an anomalous condition, by
strict denotation, this process normally occurs in
all children. The metopic suture closes within the
first year of life as a normal process and is unrecognizable in the mature skull. Computed tomographybased studies in infants, without clinical
evidence for craniosynostosis, have revealed that
all children develop some radiologic evidence for
metopic sutural fusion sometime between ages 3
and 9 months (with 100 percent showing fusion
by 9 months).58,59 This finding suggests that the
use of computed tomographic scans for diagnosing isolated metopic synostosis is probably not all
that beneficial, given this lack of specificity. Recognition of metopic sutural closure as a normal
process can help us to understand that not all craniosynostoses, per se, require surgical treatment.
Instead, it is the effects that an anomalous sutural
fusion might have on the skull (and the brain) that
determine the need for operative intervention. It

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is recognized that isolated metopic sutural ridging, in the absence of trigonocephaly, does not
require surgical treatment.60 Although some have
described surgical burring to flatten these isolated ridges, these procedures are unnecessary,
as all isolated metopic ridges efface with growth.61
It is also unclear whether partial sutural fusions
elsewhere, which do not result in any significant
alteration in skull shape, require surgical correction. Given the aforementioned two indications
for surgery (to correct appearance and to permit
normal brain function), it would seem that minimal changes in skull shape associated with partial
sutural closures are less likely to require correction, whereas more obvious changes merit correction. However, this general rule may not be
applicable for some extremely rare presentations
of multisutural fusions, as a few cases have been
described of apparently normocephalic children
with pansynostosis, who first present with clinically
detrimental elevations in intracranial pressure.62
These unusual examples of pansynostosis suggest that subtle symmetric reductions in growth,
which do not cause recognizable anomalous skull
shapes, may nevertheless negatively impact intracranial pressure and function. Another small
retrospective study has further suggested a lack
of correlation between the degree of observed
deformity and measured intracranial pressure in
a subset of children with a milder presentations
for unilateral coronal synostosis.63 Thus far, the
relationship between the severity of the alterations in skull shape occurring from craniosynostosis and measurable underlying neurologic effects
remains unclear.

TECHNIQUES
Background
A selective review of the historical evolution of
surgical techniques, and some basic sutural biology, are both helpful in determining the best way
to approach treatment. The earliest corrections for
sutural fusions (i..e, strip craniectomies) relied on
isolated removal of the fused suture.64 These early
corrections were intended to recreate functioning
sutures by simply removing the anomalous fusion.
Flummoxed by a regrowth of bone following strip
procedures, some surgeons responded by cauterizing or by wrapping the edges of bone with silastic
sheeting to prevent these bony regrowths.6567 Recognizing that these more limited procedures did
not always completely normalize skull configuration, surgeons expanded treatment from isolated
bone removal to larger remodeling procedures

Volume 133, Number 5 Craniosynostosis

(Level of Evidence: Therapeutic, IV).68 Nevertheless, reports of recurrences following both
strip craniectomies and remodeling procedures
led some surgeons to attribute their suboptimal
results to refusions or resynostoses, terms that
incorrectly imply that the cause for these failures
resides at the sutural level.69 In fact, none of the
current treatment options for craniosynostosis is
able to successfully recreate a functioning suture.
Research focused on better understanding of
both sutural anatomy and biology has improved
our understanding of the processes involved in
craniosynostosis, which in turn has helped us to
better focus our efforts to correct this condition.
It has been observed that when craniosynostosis
occurs, there is a disruption of the dural reflections (which function as chemical pathways) that
extend upward into the suture.7072 These dural
detachments are obvious to neurosurgeons when
they separate the skull from the underlying dura:
areas under functioning sutures are attached to
the dura and require careful separation, whereas
dura is easily separated from the overlying bone
under fused sutures. Simply removing a strip of
skull around a fused suture may allow the brain
to transiently undergo limited expansion, but it
cannot result in the restoration of a functioning
suture or unlock normal growth. New bone will
generally fill in the surgically created gaps in the
skulls of infants, although this regenerative ability
is gradually lost as infants mature. Thus, any procedure involving bone removal in early infancy
will be followed by a fairly rapid, albeit sometimes
incomplete, regrowth of bone that will limit the
benefits of the release. Given the variety of techniques available for treating craniosynostosis, how
does one decide which is the best? All of the various surgical approaches currently used to treat
fused calvarial sutures can be broken down into
two general groups: those involving strip craniectomies and those entailing a remodeling of the
skull. The follow is a brief description of both
approaches.
Strip Craniectomy Procedures
This general group of procedures can be further subdivided into isolated strip procedures
and strip procedures combined with some type
of postoperative skull manipulation (i.e., external
band restriction, or spring and distracter expansion). Although some studies have shown that isolated strip procedures do not provide as good a
result as remodeling procedures, many neurosurgeons still perform these procedures, especially

for isolated sagittal synostosis (Reference 73 Level

of Evidence: Therapeutic, III).73,74 Once again, it
is important to recall that although isolated strip
procedures do permit transient skull expansion,
they do not create a functioning suture, and reossification of the skull defect with bridging bone
formation is certain to occur when performed in
early infancy. Recognizing the suboptimal results
following strip procedures, and the ability of
molding devices to alter skull shapes in positional
plagiocephaly, Jimenez and Barone introduced a
hybrid technique that relies on the use of postoperative external forces by means of headbanding
with the intention of achieving a greater degree of
correction than with an isolated strip procedure
alone.75 Others have confirmed that this smaller
hybrid technique is associated with lower transfusion rates and shorter hospitalizations (Reference 77 Level of Evidence: Therapeutic, II).7678
Interestingly, Sood etal., in a small observational
study of four patients with sagittal synostosis, have
shown that improvements in skull shape are possible with just headbanding alone (which in this
study was performed before surgical intervention).79 Although the use of headbands and helmets use been shown to be efficacious in changing
skull shapes, one theoretical problem with any
technique relying on restricting skull growth
in one area to force compensatory growth elsewhere is that this process is not all that dissimilar from what is occurring with craniosynostosis.
Given that one of the rationales for treating craniosynostosis is to treat possible negative effects
on the brain caused by diminished blood flow
from raised intracranial pressure, it would seem
somewhat counterintuitive to force changes in
skull shape through the use of any device that
restricts skull growth. Nevertheless, there are no
published investigations examining the potential
for deleterious effects, such as impaired cerebral blood flow, associated with the use of either
bands or helmets. Although short-term studies
have shown that positive changes in cephalic indices are possible using banding techniques, the
long-term efficacy of postoperative molding for
normalizing three-dimensional skull shapes has
yet to be demonstrated. The opposite approach
to the reliance on restrictive forces for achieving
alterations in skull shape is the use of expansion
devices (such as springs) and distraction plates.
The use of expansion devices has the theoretical
advantage of reducing intracranial pressure and
improving cerebral blood flow by means of an
active enlargement of the calvaria. Recent retrospective reviews suggest that complication rates

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Plastic and Reconstructive Surgery May 2014

following distraction in patients with craniosynostosis are not significantly higher than with other
techniques, although the potential for device failure is recognized.8082 The use of distraction plates
would seem to provide a more accurate control
of the amount of expansion than is possible with
the use of springs (undesirable underexpansion
and overexpansion have both been reported with
spring therapy), but there have been no direct
comparative evaluations published.83 Although
the use of springs for treating craniosynostosis
has thus far not been widely adopted, retrospective analyses suggest low complication rates associated with the use of these devices.8486 Neither
of these described expansion techniques provides
active shortening; therefore, the compensatory
overgrowths are typically left uncorrected. Moreover, all expansion techniques require a second
operation to remove the expansion device. Yet
to be evaluated are the long-term requirements
for secondary skull reconstruction following any
of the aforementioned strip-based procedures,
which all include partial skull removal without
replacement.
Remodeling Procedures
All of these procedures share in common
the potential for normalization of calvarial anatomy on the operating room table through the
removal, rearrangement, and replacement of various sections of the skull. Skull remodeling, which
is the technique used by the author to treat all the
craniosynostoses, has the benefit of being able to
both expand those regions of the skull that were
affected by restricted growth (increasing cerebral
blood flow) and reduce those areas of the skull
that were affected by compensatory overgrowth,
all in a single surgical setting. However, these

procedures are associated with longer operative

times, significantly greater blood loss, and higher
transfusion rates. Skull remodeling requires
some type of bony immobilization, and numerous different bone fixation techniques have been
described. Up until the mid 1980s, surgeons relied
exclusively on stainless steel wire fixation for skull
reconstruction. However, the desire to improve
three-dimensional stability led some surgeons to
adapt metal fixation plates, originally developed
for stabilizing orthognathic osteotomies, for use
in the upper craniofacial skeleton.87 The ability
of these rigid plates to easily accomplish stable
three-dimensional reconstructions resulted in

their rapid popularity. Smaller metallic reconstruction plates were subsequently expanded into
larger, thinner mesh plates, which facilitated the
creation of stable three-dimensional forms with
multiple smaller sections of skull. However, as
experience with metal plates and screws grew, it
became obvious that anything placed on the outside of the immature skull would end up translocating intracranially with subsequent growth
(Fig.5).88 This observation helped to catalyze
the development and use of a resorbable suture
based fixation technique, which avoided the use
of any permanent materials.89 Although the use
of resorbable sutures for stabilizing skull osteotomies is both expedient and cost-effective, it is a
technically more challenging technique, primarily because of the need to design bony osteotomies in such a way that when reassembled there
will be some inherent stability. Despite published
reports citing the intracranial translocation of
metallic fixation in pediatric skull reconstruction,
the use of these plating systems persisted until
the development of resorbable plates and screws,
which remain in widespread use today. Although

Fig. 5. Metal plates, initially placed on the outside of the skull, are seen
during reoperation to have migrated intracranially with growth. This phenomenon is not unique to metallic fixation devices, and will occur with
any object placed on the growing infant skull.

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animal studies have shown that resorbable plates
are also subject to translocation with growth, and
others have observed the rare development of
sterile draining abscesses, these fixation devices
appear to be relatively safe and effective.9093
Remodeling techniques are longer surgical
procedures; they involve more extensive bone
removal and thus are associated with greater
blood loss. Multiple retrospective reviews suggest
that the majority of children undergoing cranial
remodeling procedures receive blood transfusions, and published estimates of intraoperative
blood loss reveal that blood loss may often exceed
total blood volumes.9498 Transfusions are less common with the strip craniectomy procedures, with
studies citing transfusion rates between 7 and 26
percent.76,99,100 Blood transfusions do carry the
risks of viral transmission (which has been greatly
reduced over the past 20 years), febrile reactions,
circulatory overload, allergic and transfusion
reactions,
transfusion-related lung injury, and
transfusion-related immunomodulation (immunosuppressive effects).101103 One prospective, randomized, blinded study has shown that the use
of preoperative recombinant erythropoietin was
associated with an almost 50 percent reduction
in the need for blood transfusions.104 Concerns
about the use of erythropoietin in adults, including the risks of pure red cell aplasia, increased
growth of certain cancers, increased risk of thrombosis, and increased mortality rates, led the U.S.
Food and Drug Administration in 2007 to issue
a black box warning label.105 However, it appears
likely that erythropoietin is safer in children, and a
recent multicenter retrospective review of the use
of erythropoietin in over 360 infants undergoing

cranial vault remodeling does offer reassuring

safety data.106 Moreover, any potential increased
coagulability of the blood resulting from erythropoietin administration might be beneficial in
reducing blood loss. Other intraoperative manipulations intended to reduce blood loss include
the use of hypotensive anesthesia, hemodilution
(thus far, unsupported in craniosynostosis corrections), blood recycling, and the administration
of tranexamic acid.98,107109 Combining multiple
blood salvage techniques may reduce overall
transfusion rates down to levels approaching strip
procedures.108,110 Knowledge of blood conservation strategies is an important component of
reducing surgical risks. Data culled from a survey
of craniofacial centers suggest that the most common cause for mortality following cranial vault
procedures is intraoperative blood loss.27 Aside
from blood loss, remodeling procedures appear
to have a very low overall morbidity. Postoperative
infections appear to be the most prevalent complication, with reported incidences varying from
2.5 to 6.5 percent.111113

COMPARISON OF TECHNIQUES
So, which procedure is best for correcting craniosynostosis? (See Video, Supplemental Digital
Content 2, in which Dr. Fearon discusses the best
operation for treating single-sutural synostosis,
available in the Related Videos section of the
full-text article on PRSJournal.com or, for Ovid
users, at http://links.lww.com/PRS/A989.) Given
the relative rarity of this condition, and a lack
of uniformity in outcome measurements, there
have been few comparative studies to help answer

Video 2. Supplemental Digital Content 2, in which Dr. Fearon discusses the best operation for treating single-sutural synostosis, is
available in the Related Videos section of the full-text article on PRSJournal.com or, for Ovid users, at http://links.lww.com/PRS/A989.

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Plastic and Reconstructive Surgery May 2014

this question. Windh etal. retrospectively examined sequential treatments for sagittal synostosis,
beginning first with pi procedures (which involve
removing a section of the posterior skull in a configuration similar to the Greek letter ) and later
switching to spring-assisted widening.114 They
found that their pi-plasty cranial index measurements were slightly closer to normal values, but
their spring-assisted procedures were associated
with less blood loss and shorter surgical times and
lengths of stay, confirming an earlier suggestion
of shorter operative time by Guimares-Ferreira
etal.84 Another retrospective outcome assessment of sagittal synostosis corrections suggested
that cranial indices never normalized in patients
undergoing isolated strip procedures, whereas
results were much better following remodeling
procedures.73 More recently, Shah etal. compared
sequentially treated patients with sagittal synostosis (earlier patients in this series were treated with
remodeling, and later patients were treated with
endoscopically removed strips) and found that
their endoscopically treated patients appeared
to have less blood loss, shorter operative times,
and reduced hospitalization, without significant
differences in postoperative cephalic indices.77
Finally, in spite of the fact that cranial distraction techniques significantly reduce the need for
a supradural dissection that is necessary with all
remodeling procedures, a recent comparison of
these two techniques suggested that they both had
similar safety and morbidity profiles.115 Nevertheless, all the aforementioned studies are either retrospective sequential series (allowing for potential
experience biases), or were retrospectively unrandomized (allowing for potential selection biases).
None examines results with three-dimensional
measurements. Given these shortcomings, it
seems that we have no good studies to help guide
us toward the best operative procedure for treating single-sutural craniosynostosis. There are also
no studies comparing significant morbidity or
mortality rates between the two most commonly
used techniques (strip procedures and remodeling), perhaps in part because of the rarity of these
more serious consequences. Although reducing
blood loss and shortening treatment times are
worthy goals, it is important to focus on which
technique can offer the best results (prevention
of developmental delays and three-dimensional
normalization of appearance) with the safest and
fewest number of operations (including the lowest need for subsequent secondary corrections).
General longitudinal parameters for care for treating craniosynostosis were developed following a

1270

multidisciplinary meeting at the Centers for Disease Control and Prevention in Atlanta in 2010,
with hopes of assisting with the development of
outcome sets and clinical decision making.116 Most
importantly, whatever metrics are used to evaluate
outcomes (i.e., mental development, normalization of skull shape, total number of operations,
morbidity, and mortality rates), these ideally need
to be assessed at skeletal maturity. This is because
data culled from multiple different studies suggest
that a significant number of children treated for
single-sutural synostosis will end up undergoing
repeated procedures later in life. The two most
common indications for repeated procedures are
the need to reconstruct persistent skull defects and
the need to correct recurrent abnormal skull configurations. Ideally, parents should be informed
preoperatively of not only how long an operation
should take, but also how many total operations
their child might require. Most strip procedures,
particularly those using distraction or springs,
require two operations in short succession. Considering that these procedures also involve the
removal of bone without replacement, the percentage of children who later require reconstruction of future defects needs to be assessed. Then
again, the potential need for subsequent reconstruction of persistent skull defects is not unique
to strip procedures. Remodeling techniques that
do not include an autogenous reconstruction of
all resultant skull defects may also require later
reconstruction. Aside from skull defects, a number of studies have been published that highlight
inadequate results following craniosynostosis corrections, yet it is unclear from these retrospective
studies whether these recurrences are the result
of an initial inadequate correction, poor subsequent growth, or a combination of both.69,117121
Retrospective studies using both anthropometric
measurements and computed tomographic data
suggest that following single-sutural craniosynostosis correction, growth is not normal, with a
tendency for the skull shape to recapitulate the
presenting deformity (Reference 124 Level of
Evidence: Therapeutic, IV).122124 Interestingly,
data have been recently presented that reveal
diminished frontal growth (a reduction in frontal
bossing) that appears to occur outside of the area
directly addressed following a posterior correction for sagittal synostosis.125 Published long-term
data examining reoperation rates following craniosynostosis correction are often confounded by
the inclusion of multiple types of craniosynostosis
(i.e., single-sutural, multisutural, and syndromic),
timing of surgery, operative technique, length

Volume 133, Number 5 Craniosynostosis

of follow-up, and indications for secondary procedures. Despite these variables, multiple retrospective reviews have shown that following cranial
remodeling procedures, somewhere between 6
and 36 percent of patients undergo secondary corrections (Reference 126 Level of Evidence: Therapeutic, IV).69,117,118,126128 However, none of these
studies examined outcomes exclusively at skeletal
maturity. There are no long-term data examining recurrence rates or the need for secondary
(or tertiary) procedures following strip craniectomy procedures (with either helmet therapy or
expansion), but one might expect that reoperation rates could be higher given that these techniques are not always accomplishing complete
three-dimensional reconstruction, and all include
the creation of unreconstructed skull defects.
In summary, there are currently no
well-designed studies that can help guide surgeons
toward the ideal surgical technique for correcting
craniosynostosis. Keeping in mind the overall goals
of surgery, in addition to the advantages and disadvantages of the various procedures, can help us to
pursue the ideal treatment course for our patients.

TIMING OF SURGERY
When is the ideal time to operate on craniosynostosis? Factors arguing for earlier corrections include
improved reossification in younger patients, better
results for headbanding (harnessing early rapid
growth), and a psychologically easier situation for
the parents by reducing the waiting time until surgery. Factors arguing for later surgery include better
results for remodeling (thicker bone for more stable reconstructions, and less impaired growth going
forward) and greater total blood volumes (possibly
increasing safety). There are no best-evidencetype
studies that help guide the timing for surgical intervention. Currently, surgical timing is most often
determined primarily by which surgical technique
is chosen. Strip procedures tend to be performed
as early as 6 to 12 weeks of age, based on the belief
that later surgical interventions do not achieve as
good a result, and that bony gaps are even less likely
to reossify as an infant gets older. Remodeling procedures for correcting single-sutural synostosis are
generally performed before age 1 year, but some
surgeons prefer even later corrections. We believe,
based on studies showing impaired growth following
craniosynostosis corrections, that delaying surgery
beyond 10 months might result in better outcomes
because of the rapid increase in skull growth that
occurs within the first year of life.121 The key unanswered question associated with delaying surgical

treatment for children with craniosynostosis is the

following: Do later operative interventions have the
potential to result in otherwise avoidable, permanent developmental delays? One study has identified lower intelligence quotient scores in children
undergoing correction for bicoronal synostosis after
age 1 year compared with those undergoing correction before age 1 year.129 However, this retrospective
analysis is subject to selection bias; for example, perhaps smarter parents were bringing their children
in earlier for treatment. Moreover, other observational studies seem to suggest that development in
children with sagittal synostosis is unrelated to surgical treatment.54,56 Therefore, although some data
suggest that long-term cranial morphology may be
improved with later surgical intervention, it is uncertain whether there could be any irreversibly negative
effects on development caused by such delays.

MULTISUTURAL SYNOSTOSES
Although the single-sutural synostoses represent the most common presentation for craniosynostosis, various manifestations of multisutural
synostoses have been described. These multiple
fusions have been referred to as complex craniosynostoses when no other anomalies exist, and
syndromic synostoses when there are associated
anomalies noted outside of the skull. Only a few
retrospective studies of children with complex patterns of fusion have been published.130134 Based on
reviews of treated patients, the two most common
patterns of bisutural fusion (excluding bicoronal)
appear to be (1) metopic plus sagittal and (2) unilateral coronal plus sagittal. The two most common
trisutural fusions are probably the Mercedes Benz
pattern (sagittal with both lambdoids) and the less
commonly seen Z-pattern (unilateral coronal, sagittal, and contralateral lambdoid). These complex
craniosynostoses seem to require more surgical
corrections than single-sutural synostoses (based
on observational studies) and are more likely to
develop Chiari malformations (particularly when
there is lambdoid involvement), and most do not
appear to be associated with gene mutations.135
Although relatively rare, the syndromic craniosynostoses do occur more frequently than the
complex pattern synostoses. Once again, the term
syndromic is reserved for those children with craniosynostosis who also have recurring synchronous
anomalies outside of the skull (such as midfacial
hypoplasia or limb abnormalities). Over 150 different syndromes with craniosynostosis have been
reported.136 The most common of these include
Apert, Crouzon, Pfeiffer, Muenke, S
aethre-Chotzen,

1271

Plastic and Reconstructive Surgery May 2014

and Crouzon with acanthosis nigricans. Aside from
Saethre-Chotzen, which is associated with a lossof-function mutation in the TWIST gene, all of the
aforementioned are the result of FGFR gain-of-function mutations.137 In addition to anomalous skull
growth, the syndromic synostoses may present with
varying degrees of midfacial hypoplasia, which can
result in the development of significant obstructive
sleep apnea.138 Preliminary evaluations must include
a focused airway assessment, as impaired ventilation
is probably the earliest serious risk to affected infants.
Challenges in airway management, along with the
greater potential for raised intracranial pressure
(secondary to the multiple and progressive sutural
fusions), serve to increase the complexity of caring
for children with syndromic synostosis, mandating
the need for a coordinated team approach. One retrospective case series evaluating children with Pfeiffer syndrome at a single high-volume center (Dallas)
noted a reduction in mortality rates compared with
previously published smaller studies, suggesting that
the coordination of experienced care may lead to
improve outcomes.139 More recently, a retrospective
comparative study in children with Apert syndrome
showed a strongly positive correlation from birth
between higher development levels and treatment
at our center in Dallas, using a protocol focused on
the prevention of avoidable developmental delays,
not only through monitoring for raised intracranial
pressure but also by performing early and frequent
evaluations (polysomnography) for ventilatory disturbances.140 Ideally, the care of the patient with syndromic craniosynostosis should have a primary focus
on the avoidance of preventable losses in function
(developmental delays and visual and hearing losses)
before the normalization of appearance, and with as
few operations as possible.
Jeffrey A. Fearon, M.D.
The Craniofacial Center
7777 Forest Lane, Suite C-700
Dallas, Texas 75230
cranio700@gmail.com

PATIENT CONSENT

Parents or guardians provided written consent for

use of patients images.
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