Ultrasound Diagnosis of Craniosynostosis

CAROLYN MILLER, B.A.

H. WOLFGANG LOSKEN, M.D.
RICHARD TOWBIN, M.D.
ADELBERT BOWEN, M.D.
MARK P. MOONEY, PH.D.
ALEX TOWBIN
RICHARD S. FAIX, R.D.M.S./R.V.T.
Objective: To retrospectively study prenatal ultrasound images of patients
with craniosynostosis to determine the extent to which prenatal diagnosis is
possible.
Method: Prenatal ultrasound images of 19 patients with postnatally diagnosed metopic or coronal suture craniosynostosis were retrospectively reviewed. The 26 ultrasound examinations obtained were compared with normal
images and tables of gestation.
Results: It was not possible to diagnose craniosynostosis in the first trimester. In the second trimester, Kleeblattschadel was diagnosed at 20.5 weeks.
A multilobular shape to the skull and diastasis of the frontotemporal suture
was identified. In a second child with Kleeblattschadel, the cephalic index was
above normal 86.4 (normal range 70 to 86), and the head circumference to
abdominal circumference was increased. In the third trimester, the head shape
deformation was more obvious. Brachycephaly diagnosis was made in the second trimester. In Crouzon syndrome the hypertelorism was identified at 19.9
weeks. Plagiocephaly was diagnosed at 21.4 weeks. In trigonocephaly the reduced cephalic index was noted at 18.8 weeks. In the third trimester, the deformity was diagnosed in all cases.
Conclusion: No diagnosis of craniosynostosis was made in the first trimester. In the second trimester, it was possible to diagnose Kleeblattschadel, trigonocephaly, brachycephaly (bilateral coronal suture craniosynostosis), and
plagiocephaly (unilateral coronal suture craniosynostosis) in nine of the examinations. In the third trimester and at term, it was possible to diagnose previously listed conditions from six of the seven examinations obtained. Kleeblattschadel was suspected during original examination. A total of 15 examinations of 26 were correctly diagnosed during this investigation.
KEY WORDS: craniosynostosis, prenatal, ultrasound

Craniosynostosis, the premature fusion of single or multiple

cranial sutures, may occur prenatally or perinatally (Cohen,
1986). This disorder can produce cranial deformation. The
most common sonographically diagnosed craniosynostosis reported in the literature is Kleeblattschadel (cloverleaf skull),
usually associated with thanatophoric dysplasia. Holtermuller
and Wiedemann (1960) were the first to diagnose Kleeblattschadel. Anomalies of the skull have been realized on ultrasound from 18 weeks (Witt et al., 1992). The earliest cranial
changes included abnormalities in biparietal distance (Burrows
et al., 1984; Brahman et al., 1979). Stamm et al. (1987) re-

Ms. Miller is a Student Research Assistant for Plastic and Reconstructive

Surgery, Childrens Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh,
Pennsylvania. Dr. Losken is a Clinical Associate Professor, Division of Plastic
and Reconstructive Surgery, University of Pittsburgh; Director of Pediatric
Plastic Surgery, Childrens Hospital of Pittsburgh; and Director of Medical
Services of the Cleft Palate-Craniofacial Center, Pittsburgh, Pennsylvania. Dr.
Richard Towbin is Chief, Department of Radiology, Childrens Hospital of
Philadelphia, Philadelphia, Pennsylvania. Dr. Bowen is Professor of Radiology,
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania. Dr.
Mooney is Associate Professor, Departments of Oral Medicine and Pathology,
Anthropology, Plastic Surgery, and Orthodontics, University of Pittsburgh,
Pittsburgh, Pennsylvania. Mr. Alex Towbin is a Student Research Assistant for
Plastic and Reconstructive Surgery, Childrens Hospital of Pittsburgh, Pittsburgh, Pennsylvania. Mr. Faix is a Technologist II, Department of Ultrasound,
Childrens Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania.
Presented in part at the Annual Meeting of the American Cleft PalateCraniofacial Association; April 16, 1999; Scottsdale Arizona.
This study was supported by Childrens Hospital of Pittsburgh Student Re-

search Training Program and was exempt from Human Rights Committee
(HRC) approval.
Submitted May 2000; Accepted December 2000.
Reprint requests: Carolyn M. Miller, 62 Altamont Avenue, Washington, PA
15301.
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TABLE 1 Patient Chart

Patient #

Gestational Age When

Ultrasound Performed

Postnatal Diagnosis

1
2

Kleeblattschadel/Pfeiffer syndrome
Kleeblattschadel/maxillary hypoplasia

3
4
5
6
7

Apert syndrome
Bilateral coronal suture synostosis
Plagiocephaly/unilateral coronal suture synostosis
Plagiocephaly/Saethre-Chotzen
Plagiocephaly/achondroplasia cranial dysostosis

Plagiocephaly/unilateral coronal suture synostosis

9
11
12
13
14
15

Plagiocephaly/unilateral coronal suture synostosis

Bilateral coronal suture syntosis
Plagiocephaly/unilateral coronal suture synostosis
Plagiocephaly/unilateral coronal suture synostosis
Trigonocephaly/metopic suture synostosis
Trigonocephaly/bilateral coronal 1 metopic suture synostosis

16
17
18
19

Trigonocephaly/metopic cranial suture synostosis

Crouzon syndrome/bilateral coronal suture synostosis
Crouzon syndrome/bilateral coronal suture synostosis
Saethre-Chotzen/multiple congenital/Crouzon/bilateral coronal suture synostosis
Bilateral coronal suture synostosis/hypertelorism/cranial frontal nasal dysplasia

20

ported that features of Kleeblattschadel included trilobed skull,

increased biparietal diameter, hydrocephalus, and polyhydramnios.
Crouzon, Apert, Pfeiffer and Carpenter syndromes have
been diagnosed on prenatal ultrasound images. Craniosynostosis diagnosis is made secondarily after other anatomical findings in the majority of cases. Turribrachycephaly was identified by ultrasound at 16 to 17 weeks in a child with Apert
syndrome, whose mother was similarly affected (Narayan and
Scott, 1990).
Meilstrup et al. (1995), reported unilateral coronal suture synostosis, which exhibited as an asymmetric multilobulated skull at
31.8 weeks gestation. Scaphocephaly, sagittal suture craniosynostosis, was diagnosed with ultrasound prenatally by Van der
Ham et al. (1995).
During routine ultrasound procedures, images of the skull are
measured. The biparietal distance (BPD) is preferably measured
on the transverse plane from the outer edge of the skull to the
inner opposing edge. The BPD is measured at the widest area on
the skull and demonstrates either the cerebral peduncles or thalami and the cavum of the septi pellucidi. The occipitofrontal
diameter is measured from midecho to midecho (the anteroposterior measurement obtained from outer skull to outer skull, excluding skin). The cephalic index is the ratio of the biparietal to
occipitofrontal diameters reported as a percentage. Eighty percent
is the normal intrauterine cephalic index. The cranium is considered to be brachycephalic if the cephalic index is more than 85%
and dolichocephalic if less than 75% (Jeanty and Romero, 1984).
Hadlock et al. (1981) determined that from the gestational ages
of 14 to 40 weeks, there was no significant change in the cephalic

2nd trimester17.5 weeks

2nd trimester20.5 weeks
3rd trimester29.5 weeks
3rd trimester3438 weeks
1st trimester6.5 weeks
3rd trimester35.3 weeks
2nd trimester21.4 weeks
2nd trimester21 weeks
1st trimester6.5 weeks
2nd trimester23 weeks 5 days
1st trimester6 weeks 5 days
2nd trimester17 weeks 5 days
2nd trimester16.6 weeks
3rd trimester27 weeks
Term42.1 weeks
2nd trimester29 weeks
2nd trimester18.8 weeks
2nd trimester18.9 weeks
3rd trimester32 weeks
3rd trimester36.3 weeks
2nd trimester24.2 weeks
2nd trimester19.9 weeks
2nd trimester22 weeks
2nd trimester19.7 weeks
2nd trimester23.5 weeks
2nd trimester18.6 weeks

index with gestational age. Head measurements may be correlated

with abdominal circumference or femur length. The normal head
circumference/abdominal circumference (HC/AC) is 1.07% to
1.26%. Alterations in this ratio may suggest a cranial anomaly.
The normal femur length/biparietal diameter (FL/BPD) is 71% to
87%. This ratio may be altered when there is a change in either
of these measurements.
The initial expected outcomes of this study were: (1) to find
10 patients with postnatally diagnosed craniosynostosis that
had prenatal ultrasound performed and (2) to find from these
10 patients, five instances in which craniosynostosis was discernible to our team.
METHODS
Prenatal ultrasound images of patients with postnatally diagnosed craniosynostosis were evaluated retrospectively. Results of our measurements and findings were then compared
with data of normal fetal growth and development, based on
their sonographic appearances (Patel et al., 1994; Benson et
al., 1988; Staudach, 1987; Bowerman, 1986). Craniosynostosis
and cranial deformation were specifically analyzed (Benson et
al., 1996; Kaplan et al., 1991; Furuya et al., 1984; Seeger and
Gabrielson, 1971).
A total of 109 records of patients with postnatally diagnosed
craniosynostosis of the metopic sutures, coronal sutures, or
both, either isolated or secondary to a congenital abnormality,
were initially reviewed. Forty-one patients were successfully
contacted. Twenty-two patients were eliminated because images were destroyed or did not exist. A total of 26 examina-

Miller et al., ULTRASOUND DIAGNOSIS OF CRANIOSYNOSTOSIS

75

FIGURE 1 Increased interorbital distance at 19.9 weeks gestation in patient 17 affected with Crouzons syndrome.

tions were obtained from 19 patients. Eleven of these patients

were boys, eight girls. Fourteen patients had one examination
ordered, three patients had two, and two patients had three.
Three examinations were of the first trimester, 16 of the second, six of the third, and one term. Two normal male examinations, one from the third trimester and one term, were also
included as controls. Estimating gestational age, bleeding (early pregnancy), and fetal presentation (late in pregnancy) constituted the majority of physician indication for ultrasound in
this study. An ultrasound tranducer (Acuson, Mountain View,
CA) was used for all but one set of images, which used Toshiba SAL32B linear scanner (Toshiba Information Systems,
Irvine, CA) with a 2.5-MHz transducer.

Analysis of the ultrasound images was based on the following guidelines suggested by Meilstrup et al. (1995): (1) symmetry of the calvarium contour (2) continuity of the calvarium
(to exclude encephalocele), (3) size and shape of the orbits (to
assess any deformity), (4) cerebral ventricular size (to exclude
ventriculomegaly), (5) brain parenchymal pattern (to exclude
intracranial lesion), (6) overall head size, including circumference (to help evaluate need for possible cesarean section), (7)
surrounding structures (for any extrinsic effects), and (8) detailed fetal examination (to search for skeletal or other abnormalities).
Using these guidelines, the images were viewed by three of
the authors (R.T., A.B., M.M.) who were blinded to the specific

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Cleft PalateCraniofacial Journal, January 2002, Vol. 39 No. 1

FIGURE 2 Unilateral coronal suture synostosis at 21 weeks, plagiocephaly, in patient 6.

postnatal diagnosis. One normal scan was included for every

10 images. The viewing team was not aware of the inclusion
of normal images.
The patients, their postnatal diagnosis, and their gestational
age for examinations obtained are summarized in Table 1.
RESULTS
The results of this study were: (1) 19 patients with postnatally diagnosed craniosynostosis had prenatal ultrasound performed, and (2) 12 patients with craniosynostosis were discernible.
The two normal control patients were found to be unremarkable.
First Trimester
Diagnosis was not possible in the first trimester. All aspects
of pregnancy appeared normal on report and to the three viewers.
Second Trimester
Crouzons syndrome. Patient 17 was affected with Crouzons syndrome. Brachycephaly caused by bilateral coronal suture synostosis was noted. Increased interorbital distance was
noted, denoting hypertelorism. This syndrome was correctly

identified (Fig. 1). Patient 18 demonstrated a short, round,

brachycephalic head shape.
Saethre-Chotzen syndrome: Patient 19 was correctly diagnosed at 19.7 weeks with an abnormal head shape. The cranium of the same patient at 23.4 weeks was brachycephalic
and almost square. The HC/AC fell below the normal range
of 1.07% to 1.26% for both sets of images. At 19.7 weeks
gestation, the HC/AC was 0.99% and at 23.4 weeks, 1.03%.
Bilateral coronal suture synostosis. No cranial deformation
was recognized at 18.6 weeks for patient 20.
Plagiocephaly (unilateral coronal suture synostosis). Unilateral anterior cranial flattening occurred in patient 5 and was
correctly diagnosed in the second trimester. The cephalic index
(CI) was 75%, and the HC/AC (1.05%) fell below normal. In
patient 7, images exhibited cranial deformation and abnormal
shape and bulging, enlarged ventricles, asymmetric head, and
possible cyst (abnormal ventricles a result of achondroplasia).
The FL/BPD was 65.2 (71 to 87). Achondroplasia was suspected in utero. Plagiocephaly was not recognized for patient
13 or 8. In patient 9, unilateral coronal suture synostosis was
misdiagnosed as metopic suture synostosis. Tapering occurred
at midline. Patient 6 exhibited plagiocephaly with frontal flatness on the affected side (Fig. 2).
Trigonocephaly. In patient 14, trigonocephaly was diagnosed correctly, with a short anteroposterior dimension,
brachycephaly, and mild ventricular enlargement (Fig. 3). Pa-

Miller et al., ULTRASOUND DIAGNOSIS OF CRANIOSYNOSTOSIS

77

FIGURE 3 Trigonocephaly, manifested as a brachycephalic head shape at 18.8 weeks gestation, for patient 14.

tient 16 exhibited a brachycephalic head shape but was believed to have unilateral coronal suture synostosis. Patient 15s
images appeared normal at 18.9 weeks.
Kleeblattschadel. Kleeblattschadel was not diagnosed from
the images of patient 1, at 17.5 weeks, but the deviation in the
CI of 86.4 (70 to 86) and the HC/AC of 1.27 (1.07 to 1.26)
suggested possible problems. Kleeblattschadel in patient 2 was

correctly diagnosed with slight abnormality of the cranium,

which exhibited widening posteriorly (Fig. 4A).
Third Trimester
Kleeblattschadel. Two sets of images were available from
the third trimester for patient 2, the first at 29.5 weeks and the

FIGURE 4 Kleeblattschadel. A: in patient 2 at 20.5 gestational weeks; B: multilobular-shaped cranium in patient 2 at 29.5 gestational weeks.

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Cleft PalateCraniofacial Journal, January 2002, Vol. 39 No. 1

TABLE 2 Previously Reported Cases of in Utero Diagnosis

Author

Brahman et al. (1979)

Witt et al. (1992)
Saal et al. (1995)
Stamm et al. (1987)
Burrows et al. (1984)
Weiner et al. (1986)
Mahony et al. (1985)
Chervenak et al. (1983)
Sergi et al. (1997)
Leo et al. (1991)
Gollin et al. (1993)
Menashe et al. (1989)
Filkins et al. (1997)
Narayan and Scott (1990)
Chenoweth-Mitchell and Cohen (1994)
Parent et al. (1994)
Kim et al. (1986)
Hill et al. (1987)
Kaufman et al. (1999)
Hill and Grzybek (1994)
Balci et al. (1997)
Meilstrup et al. (1995)
Van Der Ham et al. (1995)

Diagnosis

Gestational Age at Diagnosis

Kleeblattschadel
Kleeblattschadel
Kleeblattschadel
Kleeblattschadel (4)
Thanatophoric dysplasia
Kleeblattschadel
Thanatophoric dysplasia
Kleeblattschadel
Thanatophoric dysplasia
Kleeblattschadel
Thanatophoric dysplasia
Kleeblattschadel
Thanatophoric dysplasia
Crouzon syndrome
Crouzon syndrome
Crouzon syndrome
Crouzon syndrome
Apert syndrome
Apert syndrome
Apert syndrome
Apert syndrome
Apert syndrome
Apert syndrome
Apert syndrome
Pfeiffer syndrome
Carpenter syndrome
Unilateral coronal craniosynostosis
Scaphocephaly

second at 34 to 38 weeks. At 29.5 weeks (Fig. 4B), there was

a multilobular shape to the cranium. Diastasis of the right frontotemporal suture was noted in the report. At 34 to 38 weeks,
the ventricular enlargement or multifocal cysts, and cranial deformation were visualized. Enlarged ventricles report as well
as disproportionate increase in the size of the skull were noted
on the ultrasound.
Bilateral coronal suture synostosis. Patient 4 was correctly
identified; however, images were of poor quality. The CI was
D1 to 94.7 mm (biparietal diameter) and D2 to 105.4 mm
(occipitofrontal diameter), giving this patient a brachycephalic
head shape. Patient 11 was not correctly diagnosed with plagiocephaly but was brachycephalic on the images.
Trigonocephaly. Two sets of images were available for patient 15 in the third trimester. The head became rounder and
shorter; within 4 weeks the head changed from trigonocephaly
features to brachycephalic in shape. The HC/AC at 32 weeks
gestation was 1.01% and at 36 weeks gestation, 1.02%.
Control. A normal examination of a male fetus at 33.3
weeks gestational age was correctly diagnosed as unremarkable.
Term
Plagiocephaly (unilateral coronal suture synostosis). At
42.1 prenatal weeks, patient 12 was correctly diagnosed with
anterior cranial flattening on the affected side. The HC/AC was
1.00%.
Control. A normal examination, the male sibling of patient
12, was found to be unremarkable at 41.3 gestational weeks.

18 weeks
18 weeks
32 weeks

19.7 weeks
22 weeks
30 weeks
32 weeks
19 weeks
21 weeks
23 weeks
35 weeks
1st trimester
16.5 weeks
26.5 weeks
28 weeks
28 weeks
31.8 weeks
28 weeks
35.4 weeks
20 weeks
31.8 weeks
34 weeks

DISCUSSION
In the United States, 23 indications for obstetrical ultrasound
are listed by the National Institute of Health Consensus Panel.
Obstetric ultrasonography is performed in 40% to 60% of the
pregnancies in the United States. It is perceived as a harmless
method for obtaining valuable clinical information (Hughey,
1987).
Ossification centers become visible near the end of the first
trimester. At 16 weeks the sagittal scan displays the cranium
and the echo-free fontanel and cranial sutures. (Staudach,
1987). On an axial sonogram at the beginning of the second
trimester, the head is oval. Based on the images presented by
Benson et al. (1988), the optimal time for viewing echo-free
sutures is from 14 weeks to 16 weeks. Cranial curvature makes
it difficult to assess structural continuity with two-dimensional
ultrasonography (2DUS). The viewer may not obtain sufficient
information from a single 2DUS static image. Real-time 2DUS
scanning is needed to identify the cranial sutures and fontanels
(Pretorius and Nelson, 1994) This shortcoming of 2DUS static
images was apparent in our study.
Craniosynostosis has been diagnosed in utero with the assistance of ultrasonography primarily in isolated single instances (Table 2). Redirection of brain and calverial growth at
sites distant from the sutures occurs as a result of craniosynostosis (Fernback and Naidich, 1986). From the images obtained, it was possible for our team to diagnose craniosynostosis utilizing secondary sonographic signs. The secondary deformation did not manifest itself in utero until the second trimester. Later first-trimester images (obtained at 6.5 weeks)

Miller et al., ULTRASOUND DIAGNOSIS OF CRANIOSYNOSTOSIS

may prove useful in determining when secondary deformation

commences.
Hegge et al. (1990) reported the detection rate for ultrasound
abnormality to be 1.2 malformations per 100 fetuses, 13% of
all malformations and about 27% of major malformations. Craniosynostosis has a detection of 52 per 100,000 (Hegge et al.,
1990). In the Hegge series, none of these were detected with
prenatal ultrasound. Hill et al. (1985) diagnosed nine skeletal
abnormalities prenatally with ultrasound, but craniosynostosis
was not correctly diagnosed. The sonogram showed the calvarium to be long and narrow in one patient in their series.
The biparietal diameter was 6 weeks behind the stated gestational age of 38 weeks. They state that craniosynostosis was
not suspected at the time of scanning, but the application of
current obstetric techniques (cephalic index, head circumference, and femur:biparietal diameter ratio) might lead one to
suspect the correct diagnosis. Hadlock et al. (1981) demonstrated that a significant change in the fetal skull shape might
alter the BPD.
In our study, unilateral coronal suture synostosis was diagnosed as early as 21.4 weeks. To our knowledge, unilateral
craniosynostosis has not previously been detected at this early
gestational age. Diagnosis was made from cranial deformation.
Anterior flattening of the cranium occurred unilaterally. Intracranial anatomy appeared normal. Meilstrup et al. (1995) diagnosed asymmetric craniosynostosis at 31.8 weeks; however,
the images appeared similar to a Kleeblattschadel cranium.
Antenatal sonographic detection of Kleeblattschadel in our
study was achieved from images demonstrating bilateral bulging of the temporal lobes with an intact bony calvarium. Kleeblattschadel was not associated with thanatophoric dwarfism
in our two cases. At 20.5 weeks the calvarium was abnormally
shaped but not trilobular. In the third trimester, the cloverleaf
skull shape manifested on ultrasound. Postnatally patients 1
and 2 experienced elevated intracranial pressure.
Postnatally trigonocephaly has been diagnosed by computer
tomography (CT) scanning. Furuya et al. (1984) demonstrated
a CT scan with anteriorly pointed cranial vault and thickening
at the site of the metopic suture. Using this diagnostic reference, we were able to diagnose trigonocephaly in utero at 18.8
weeks. Postnatally one patient developed significant trigonocephaly. Trigonocephaly has not been diagnosed prenatally to
our knowledge. Trigonocephaly presented as brachycephaly in
the third trimester. Bilateral coronal suture synostosis resulted
in a short anteroposterior diameter.
Facial anomalies and increased interorbital distance were
present on the images of patients with Crouzons syndrome as
early as 19.9 weeks gestation.
CONCLUSION
This retrospective study was undertaken to determine
whether prenatal ultrasound images, taken during routine procedures, could be applied toward diagnosis of craniosynostosis
in utero. Specifically, our aim was to report on any correlation
of diagnosis made prenatally from images obtained and the

79

actual postnatal diagnosis and to define ultrasound diagnostic

criteria for future use.
Early detection of craniosynostosis may decrease complications during delivery and facilitate postnatal management.
Once craniosynostosis is detected in utero, five therapeutic alternatives are possible: (1) selective abortion, (2) correction
after term delivery, (3) induced preterm delivery for early neonatal therapy, (4) prophylactic delivery by cesarean section to
reduce fetal trauma, and (5) therapy in utero (Harrison et al.,
1981; Hill et al., 1985).
Comparative studies to establish diagnostic criteria may help
eliminate misdiagnosis of Kleeblattschadel as an encephalocele
(Stamm et al., 1987). Early diagnosis of Kleeblattschadel may
facilitate intrauterine surgery. Whether intrauterine surgery
would be a proposition in the future is something we cannot
answer now. Kaplan et al. (1991) state that mental retardation
is highest in patients with multiple synostosis and increased
intracranial pressure and in whom surgery is performed at a
later age. Research on intrauterine surgery to remove fused
suture has been performed on lambs with unilateral coronal
suture synostosis with promising results. Significant improvement occurred with correction of craniosynostosis in utero. In
utero repair prevented the formation of secondary deformation
(Stelnicki et al., 1998). Stelnicki et al. (1998) state that it is
reasonable to hypothesize that any prenatal intervention to correct craniosynostosis and prevent secondary deformations
would be beneficial.
Detection of abnormality is continuing to increase as we
define criteria for abnormal conditions (Shirley et al., 1992).
In a series in which the majority of images have diagnostic
problems, further images should be ordered to increase diagnostic capabilities.
Postnatally, cranial deformation was confirmed radiologically for our patients. All patients required postnatal surgery.
We are hopeful that further study will result in an increased
sensitivity to accurate diagnosis of craniosynostosis in utero.
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