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3 Diagnosis andClassication ofCraniosynostoses
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Fig. 3.6 The dura mater has a great impact on the ossication process via mechanical and biomechanical interactions.
(Source: Shutterstock)
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Types ofCraniosynostoses
On a clinical level, craniosynostosis patients
present with different skull shapes [9–12].
Therefore, the feature of the skull shape is given
the name of the craniosynostosis type (Fig.3.7).
Patients with positional plagiocephaly present
with different head shapes, compared to nonsyndromic craniosynostosis, and these patients
again present with different head shapes compared to syndromic patients [13]. The types of
head shapes are named according to the geometry
of the skull from a top view (Fig.3.8). Typical
ndings are present in non-syndromic patients
with an involvement of a single suture, whereas
multiple suture involvement leads to a more complex head deformation. Premature single-suture
ossication leads to a predetermined skull morphology that can be distinguished as follows:
Positional Plagiocephaly
The term plagiocephaly means oblique skull and
corresponds to a unilateral or bilateral occipital
attening, which may arise due to the continual
inuence of external forces on the immature skull
(positional posterior plagiocephaly) (Fig. 3.9).
This deformity results from an ongoing action of
deformational forces on the occipital region,
causing a attened region of the posterior craniofacial skeleton. If no intervention is performed,
the deformity can continue and, in multiple cases,
leads to facial deformities to different extents
(Fig.3.10a). Positional or deformational plagiocephaly is the most common cause of
plagiocephaly (prevalence of 5–48% in healthy
newborn infants) compared to an incidence of
0.003% of synostotic plagiocephaly (lambdoid
synostosis). Based on the introduction of the
campaign to prevent sudden infant death syndrome (“back to sleep”), in the beginning of the
1990s—which recommended that babies remain
in the supine position—a signicant increase in
the incidence of children with positional plagiocephaly was noticed (5–48%).
The morphologic classication here is presented through the ossication disturbance of
sutures, starting from the most anterior to the
most posterior suture (Fig.3.10).
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Front viewLateral view
Front viewLateral view
Plagiocephaly
Plagiocephaly
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U. Meyer
Cranial Deformities
Normal head shape
Front viewLateral view
Brachycephaly
Oblique view
Oblique view
Front viewLateral view
Plagiocephaly
Oblique view
Scaphocephaly
Oblique view
Fig. 3.7 Schematic drawing of the child’s head appearance in dependance on dened premature single-suture ossications. (Source: Shutterstock)
Craniosynostosis
Nomocephaly
Posterior
Fig. 3.8 Single-suture ossications with the indicated resulting growth and the resulting skull shape. (Source:
Shutterstock)
Tr igonocephaly
Anterior
Scaphocephaly
Brachycephaly
Oblique viewOblique viewFront view
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Trigonocephaly
Trigonocephaly results from a premature fusion
of the metopic suture. The back of the head is
broad, and the forehead is narrow and pointed.
When viewed from above, the forehead has a
triangular shape (Fig. 3.10b). The orbits are
abnormally close together (hypotelorism).
Plagiocephaly
Normal head shape
Plagiocephaly Plagiocephaly
Anterior Plagiocephaly
Anterior plagiocephaly results from a premature fusion of a one-sided coronal suture. On
the affected side, the forehead is attened
because of arrested growth, and higher supraorbital margins form a characteristic sign on
radiographs, known as the Harlequin sign
Fig. 3.9 Schematic drawing of a child with positional plagiocephaly. (Source: Shutterstock)
a1 a2
Fig. 3.10 Typical clinical ndings of the various skull
types from a frontal (1) and top (2) view. (Source: Ulrich
Meyer, informed consent of patients exists). (a)
Deformational plagiocephaly. (b) Trigonocephaly. (c)
Anterior plagiocephaly. (d) Crouzon syndrome (threeskull phenotype alteration through growth). (e) Pfeiffer
syndrome
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b1 b2
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c1 c2
U. Meyer
d1
Fig. 3.10 (continued)
d2
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d3
e2
e1
Fig. 3.10 (continued)
(Fig. 3.10c). On the opposite side, the
forehead is pushed forward. Additional ndings include at cheeks on the side of synostosis and nasal septum deviation towards the
affected side.
Brachycephaly
Brachycephaly is a bilateral coronal synostosis.
As a result of the fused coronal suture, the skull
is short. The forehead and occipital part are attened, and the frontal bone is prominent and
elongated in a vertical direction. The orbits are
abnormally separated (hypertelorism), and the
Harlequin malformation of the orbits is seen on
radiographs.
Scaphocephaly
In this type of synostosis, there is a premature
fusion of the sagittal suture. It is commonly
observed in premature infants. The head is typically elongated in the anterior-posterior direction
and shortened in the bilateral direction. In some
children, frontal bossing is present and the ridging of the sagittal suture is palpable. Boys are
more frequently affected than girls, with a ratio
of 3.5:1.
Posterior Plagiocephaly
Posterior plagiocephaly is a unilateral lambdoid
synostosis. Frontal and occipital bossing can
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U. Meyer
develop contralateral to the affected side. The
ipsilateral ear and mastoid can be displaced
downward. In the majority of cases, the ear is
also displaced in the anteroposterior direction.
Clinically, the shape of the head from above can
resemble a trapezoid.
Syndromic Craniosynostosis
Patients with syndromic craniosynostosis present
with a much greater deformation of the whole
skull. The kind and extent of the dysmorphic features are dependent on the type of craniosynostosis and the disease severity. Additionally, the face
presents also signicant dysmorphological signs
(hyper- or hypotelorism; hypoplasia of midface;
facial asymmetry; position, shape, and size of the
ears) (Fig.3.10d, e).
Diagnostic Issues
Inclusion of patients into the nal classication
scheme is then dependent on a subsequent diagnostic approach. The diagnostic approach can be
conceptualized in three steps: rst to distinguish
deformational plagiocephaly from craniosynostosis [13]; second to differentiate non-syndromal
craniosynostosis from syndromal craniosynostosis; and third to evaluate the type of craniosynostosis in syndromal cases. The diagnosis of a
typical craniosynostosis is usually clinical, and it
is commonly diagnosed in the rst year of life.
Cranial deformities are a common nding in
newborns, since 25% of infants of single pregnancies and 50% of multiple pregnancies have
some degree of skull deformity at birth [14]. To
distinguish between a positional plagiocephaly
and a craniosynostosis, the physical examination
and clinical history are the most helpful and
revealing pieces of information in the child’s
evaluation. The kind of head shape is the most
important parameter of differentiation.
The examination approach should generally
start with a thorough family history and a detailed
clinical examination. Radiographic assessment
should be performed in unclear cases and prior
surgery. Experienced physicians, familiar with
such diseases, are able to recognize skull deformities and to diagnose them as either craniosynostosis or a positional skull deformity. Key
aspects to differentiate the craniosynostoses from
the positional deformities can be revealed by two
questions: (1) “Is deformity present at birth?” (2)
“Is there improvement of the deformity over
time?” (1) Craniosynostosis is present at birth,
whereas nonsynostotic deformities develop
mostly in the neonatal period. (2) Craniosynostosis
gets worse with time, whereas the positional
deformities improve as the child develops head
control and the skull no longer has localized pressure for long periods.
Additionally, the next step of the craniosynostosis patient classication is whether it is a syndromic or non-syndromic form. The shape of the
skull is often the leading differentiation aspect
between a syndromic and non-syndromic case
(Fig. 3.10). Non-syndromic patients present in
general with a classic skull form. Additionally,
the facial structures are only involved to a minor
extent [involvement is greater, when anteriorly
located sutures are involved (metopic, coronal)].
Three aspects have to be assessed, if a syndromal condition is expected. If a syndromal craniosynostosis is diagnosed, patients should undergo
an interdisciplinary assessment. Such an assessment should involve a sleep study; audiological
testing; ophthalmology consultation with fundoscopic examination; electrodiagnostic tests
(EDTs); optical coherence tomography (OCT),
as indicated; psychological assessment, with
questionnaires directed at their quality of life,
expectations, and feelings about their treatment;
developmental assessment (Ages and Stages
Questionnaire); speech, language, and feeding
evaluation; a dental and orthodontic review; as
well as an ear, nose, and throat investigation.
First, the patient’s morphological alterations
should be determined more precisely. The clinical examination includes the assessment of typical signs, especially possible congenital
anomalies (e.g., a broad, radially deviated thumb
in Pfeiffer syndrome or syndactyly in Apert syndrome), dysmorphic features of the face (hyperor hypotelorism, hypoplasia of midface,
asymmetry, and position, shape, and size of the
ears), skull shape from all directions, and mea-
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ab
cd
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Fig. 3.11 CT features of the various skull types, demonstrating the increasing extent of skull deformation.
(Source: Ulrich Meyer, informed consent of patients
surement of the head circumference for calculating the cephalic index (the ratio of maximum
breadth to maximum length of the skull). The
clinical investigation during the postpartum time
should search for any sutural ridging, prominent
blood vessels on the scalp, and size, shape, and
tension of the fontanelles. For the evaluation of
an increased ICP, ophthalmological examination
exists). *Details of gene ndings are given in Refs. [15–
29]. (a) Trigonocephalus. (b) Anterior plagiocephaly. (c)
Apert syndrome. (d) Crouzon syndrome
is of great importance. In cases with increased
ICP, papilledema is present.
In craniosynostosis cases, especially the syndromic ones, computed tomography (CT) with
three-dimensional (3D) reconstruction is considered the most complete and accurate imaging in
diagnostics (Fig. 3.11). With a CT scan, all
sutures can be assessed for patency [30–32]. In
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Fig. 3.12 MRI picture of a patient with Crouzon
syndrome
U. Meyer
addition, the CT scanning allows evaluating the
brain for possible structural abnormalities (e.g.,
ventriculomegaly, agenesis of the corpus callosum, and craniocerebral asymmetry). The magnetic resonance imaging (MRI) is an excellent
additional technique for the evaluation of brain
(Fig.3.12), albeit less accurate in visualizing the
cranial sutures compared to CT.Generally, MRI
is reserved for patients in which CT reveals cerebral anomalies. An angio-MRI investigation
(Fig.3.13) is reasonable in special cases. The use
of an ultrasound examination, as a third imaging
procedure, is a fast, low-cost, radiation-free
method that requires no sedation. However, it is
applicable only in cases in the absence of other
craniofacial malformations. It may be a feasible
method for diagnosing simple, non-syndromic
craniosynostosis in utero.
Second, the pathophysiology of the disease
should be determined. To evaluate the etiology of
syndromal craniosynostosis and the search for
possible comorbidities, the focus is on the family
history of unusual head shapes, prenatal exposure
to teratogens (e.g., valproic acid), evidence of
intrauterine constraint due to multiple pregnancy,
primiparity, abnormal fetal position, oligohydramnios, or other abnormal fetal anatomical
features.
Third, genetic testing should clarify the nal
diagnosis. Additionally, from a patient-driven
approach, one aspect is of special relevance,
whether urgent or elective management is
required.
Fig. 3.13 Vessel localization of a patient with Crouzon
syndrome
Classication
After a thorough evaluation, classication is the
nal step of disease determination. The classication of craniosynostosis should therefore
include the genetics, the pathophysiology, and
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39
the resulting morphology, reecting the type and
the severity of the disease. Different classication schemes of craniosynostosis are used
depending on the underlying biology, presence of
other disorders, or number of fused sutures. The
insight into genetic aspects of syndromal
craniosynostosis types [15–20, 33–35] is grown
over time and has inuenced the way of disease
classication.
1. Craniosynostosis types can be classied
according to the involved sutures. Simple craniosynostosis is a term used when only one
suture fuses prematurely, while complex cra-
Table 3.3 Types of craniosynostosis development
Primary • Simple (metopic, coronal, saggital,
lambdoid)
• Complex non-syndromic (combination of
more then one)
• Syndromic (Apert, Crouzon, Pfeiffer,
Saethre-Chosten, others)
Secondary • Metabolic (hyperthroidism,
mucopolysaccharidosis, others)
• Exposure to substances (phenytoin,
valproic acid, others)
• Mechanically driven (microcephaly,
encephalocele, drainage of CSF)
niosynostosis is used to describe a premature
fusion of multiple sutures.
2. From the biological point of view, craniosynostosis can be classied according to the
underlying course of the premature mineralization process (Table 3.3). If a craniosynostosis develops due to a primary defect of the
ossication process, it is called primary craniosynostosis. On the other hand, secondary
craniosynostosis is the result of known systemic diseases with hematologic or metabolic
dysfunction, such as rickets and hypothyroidism. Secondary craniosynostosis can also
develop in newborns with microcephaly due
to a failure of brain growth or following shunt
placement in children with hydrocephalus.
3. Simple craniosynostosis can be classied
according to the resulting morphology
(reecting the involved suture).
4. Furthermore, craniosynostosis can be classied into non-syndromic (where it develops as
an isolated disorder) or syndromic, e.g., as
part of Apert, Crouzon, Saethre-Chotzen, or
Pfeiffer syndrome [21–24, 36–42]. There are
some strategies, concerning clinically driven
genetic testing of syndromal craniosynostosis
patients (Table3.4).
Table 3.4 Types of syndromal craniosynostosis diseases, their underlying genetics, and common clinical features
Syndrome Inheritance Gene Typical suture Special clinical features
• Apert AD (n) FGFR 2 Coronal, multi s. Comlex syndactily
• Crouzon AD FGFR2 Multis., cor., sagg. Exorbitism, beaked nose
• Pfeiffer AD FGFR1 Multis. Cloverleaf skull, fused elbows
• Saethre-Chotzen AD TWIST1 Coronal Hypertelorism, low hairline
• Muenke AD (n) FGFR3 Coronal Hearing loss, brachydactyly
• Bohring-Opitz AD (n) ASXL1 Metopic Ulnar deviation, naevus amm.
• Craniofrontonasal XLD EFNB1 Coronal Hypertelorism, notched nas. tip
• Beare-Stevenson AD (n) FGF2 Multis. Chonal atresie
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U. Meyer
Conclusion
The distinction between a positional plagiocephaly and craniosynostosis is usually made clinically by inspection. Also, the classication of
patients within the single-suture craniosynostosis
group is mainly done on the morphology of the
skull. Syndromal craniosynostosis patients can
be differentiated towards early single-suture ossications by the concomitant dysmorphic facial
features. For the classication in between the
syndromal craniosynostosis group, additional
investigations have to be performed. The genetic
evaluation is of major importance in such
patients. A thorough clinical and radiological
investigation is important to determine the extent
of the disease as well as to establish an elaborated
treatment plan.
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