ß 2007 Wiley-Liss, Inc.

American Journal of Medical Genetics Part A 143A:3243 – 3251 (2007)

The Morphogenesis of Wormian Bones: A Study of

Craniosynostosis and Purposeful Cranial Deformation
Pedro A. Sanchez-Lara,1 John M. Graham Jr,1* Anne V. Hing,2 John Lee,1 and Michael Cunningham2
1
Medical Genetics Institute, Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, California
2
Division of Craniofacial Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington
Received 14 June 2007; Accepted 20 August 2007

Wormian bones are accessory bones that occur within
cranial suture and fontanelles, most commonly within the
posterior sutures. They occur more frequently in disorders
that have reduced cranial ossification, hypotonia or decreas-
ed movement, thereby resulting in deformational brachyce-
phaly. The frequency and location of wormian bones varies
with the type and severity of cranial deformation practiced
by ancient cultures. We considered the hypothesis that the
pathogenesis of wormian bones may be due to environ-
mental variations in dural strain within open sutures and
fontanelles. In order to explore this further, we measured
the cephalic index (CI) in 20 purposefully deformed pre-
Columbian skulls: 10 from Chichen Itza, Mexico, and 10 from
Ancon, Peru, as well as 20 anatomically normal skulls used
for medical school anatomy classes. We tested for a direct
correlation between the CI and the number of wormian
bones in skulls with varying degrees of brachycephalic
cranial deformation and found no significant correlation.
When the CI was grouped into three categories (normal
(CI < 81), brachycephalic (CI 81-93), and severely brachy-
cephalic (CI > 93)) there was a trend toward increasing
number of wormian bones as the skull became more
brachycephalic (P ¼ 0.039). A second part or our study
tabulated the frequency and location of large wormian bones
(greater than 1 cm) in 3-dimentional computerized tomog-
raphy (3D-CT) scans from 207 cases of craniosynostosis and
compared these data with published data on 485 normal dry
skulls from a manuscript on wormian bones by Parker in
1905. Among cases of craniosynostosis, large wormian bones
were significantly more frequent (117 out of 207 3D-CT
scans) than in dry skulls (131 out of 485). There was a
3.5 greater odds of developing a wormian bone with
premature suture closure (P < 0.001). Midline synostosis,
specifically metopic or sagittal synostosis, has more wormian
bones in the midline, whereas unilateral lambdoidal or
coronal synostosis more often had wormian bones on the
contralateral side. Taken together, these data suggest that
wormian bones may arise as a consequence of mechanical
factors that spread sutures apart and affect dural strain within
sutures and fontanelles. ß 2007 Wiley-Liss, Inc.
Key words: wormian bones; deformation, plagiocephaly;
craniosynostosis; calvarial morphogenesis; cultural cranial
deformation; Ancon skulls; Chichen Itza skulls; sagittal
synostosis; metopic synostosis

How to cite this article: Sanchez-Lara PA, Graham JM Jr, Hing AV, Lee J, Cunningham M. 2007.
The morphogenesis of wormian bones: A study of craniosynostosis and purposeful
cranial deformation. Am J Med Genet Part A 143A:3243–3251.

INTRODUCTION
Wormian bones are accessory skull bones com-
pletely surrounded by a suture line. They were first
characterized by the Danish anatomist Olaus Worm
in a letter to Thomas Bartholin (April 6, 1643). Their
developmental pathogenesis has been discussed
since their discovery, with hypotheses involving
both environmental and genetic influences. In 1897,
Dorsey proposed that the frequency of wormian
bones was influenced by pressure on the cranium
from cultural cranial deformation. Several studies
have since proposed various hypotheses, from solely
environmental stressors affecting the incidence of
wormian bones to primary genetic factors with little
Grant sponsor: HARE’s Childhood Disability Center; Grant sponsor:
Steven Spielberg Pediatric Research Center; Grant sponsor: Cedars-Sinai
Burns and Allen Research Institute; Grant sponsor: Skeletal Dysplasias
NIH/NICHD Program Project; Grant number: (HD22657-11); Grant
sponsor: Medical Genetics NIH/NIGMS Training Program; Grant
number: (GM08243); Grant sponsor: National Institute of Craniofacial
and Dental Research (MLC); Grant number: R01- DE 13813; Grant
sponsor: Laurel Foundation Center for Craniofacial Research (MLC);
Grant sponsor: Jean Renny Cranofacial Endowment (MLC).
*Correspondence to: John M. Graham, Jr, Director of Clinical Genetics
and Dysmorphology, Cedars-Sinai Medical Center, 8700 Beverly Blvd,
Suite 1150W, Los Angeles, CA 90048. E-mail: john.graham@cshs.org
DOI 10.1002/ajmg.a.32073
 American Journal of Medical Genetics Part A: DOI 10.1002/ajmg.a
3244 SANCHEZ-LARA ET AL.
or no environmental influence. Anthropological
research has demonstrated that circumferentially
deformed crania have fewer wormian bones than
undeformed crania, and anteroposteriorly deformed
crania have the most wormian bones [White, 1996;
O’Loughlin, 2004].
There are also genetic factors that impact wormian
bone development, be it directly or indirectly. In a
number of genetic syndromes, wormian bones are so
common that they are often considered primary
characteristics or are included in their diagnostic
criteria (Table I) [Stevenson and Hall, 2006; Lachman
and Taybi, 2007; McKusick, 2007]. Some disorders
result in intracranial forces that spread open sutures
(e.g., hydrocephaly). Other syndromes have asso-
ciated metabolic bone disease that reduces skull
ossification, resulting in wider sutures and fonta-
nelles with brachycephalic cranial deformation
(e.g., osteogenesis imperfecta and cleidocranial
dysplasia). Still others have associated hypotonia
and neurocognitive delay (e.g., Down syndrome) or
decreased movement (e.g., SC Phocomelia). Such
infants become brachycephalic as a consequence of
occipital pressure from postnatal supine positioning
on soft cranial bones, as do infants with generalized
hypotonia or limited movement. Chinese crania also
manifest more wormian bones than in crania from
western cultures, and this finding may relate to their
longer tradition of supine infant sleep positioning
resulting in deformational brachycephaly [Graham
et al., 2005]. Given these observations, it is possible
that wormian bones arise in sutures as a conse-
quence of variations in dural strain across widened
posterior sutures from external cranial deforma-
tion. It is difficult to separate the influence of
deformational brachycephaly from that of reduced
calvarial mineralization, since such skulls are more
malleable for a longer period of time than skulls with
normal mineralization.
Recent observations suggest that there is also an
increased frequency of wormian bones in craniosy-
nostosis. O’Loughlin [2004] had noted that wormian
bones occurred more frequently in the lambdoid
sutures with sagittal synostosis, but very few skulls
were available for study. One recent study of intra-
operative skulls found that a wormian bone replaced
the anterior fontanelle in 4 out of 100 sagittal
synostosis cases [Agrawal et al., 2006]. Such anterior
fontanelle wormian bones are extremely rare. In
rabbits with experimental coronal synostosis, wor-
mian bones appear in the coronal and sagittal sutures
after the onset of cranial growth alterations induced
by premature coronal synostosis. These findings
suggest that wormian bones may form in relation to
increased sutural width and dural strain due to
external mechanical factors [Burrows et al., 1997].
The location of the excess in wormian bones in
relation to the site of craniosynostosis may shed light
on this process.
We considered the pathogenesis of wormian
bones and its relationship to variations in sutural
width and dural strain from cranial deformation. If
brachycephalic deformation results in increased
wormian bone formation, then one might expect
the number of wormian bones to directly correlate
with more severe occipital flattening. The increased
prevalence of wormian bones in ancient cultures
practicing fronto-occipital head binding suggests
that these bones may form in relation to the degree of
brachycephaly, resulting in widening of posterior
sutures along with increased dural strain. Craniosy-
nostosis also increases sutural and fontanelle width
in relation to the location of the initiation site of
the craniosynostosis. In this study, we noted the
frequency and location of wormian bones in either
non-syndromic craniosynostosis or purposefully
deformed skulls, and we compared our findings
with anatomically normal skulls. Given that non-
syndromic craniosynostosis occurs prenatally, while
cultural cranial deformation occurs postnatally, this
study allowed us to compare the effects of different
types of mechanical forces occurring in either late
gestation or early infancy on the frequency and
location of wormian bones.
METHODS
To investigate our hypothesis that wormian bones
formed in relation to mechanical factors, we com-
pared 20 normal skulls from the UCLA Anatomy
and Anthropology Departmental collection with 20
purposefully deformed skulls from the Peabody
Museum of Anthropology. Of the Peabody collec-
tion, 10 skulls were from Chichen Itza Mexico, and
10 skulls were from Ancon Peru. These cultures
typically used molding devices that applied pressure
against the occiput [O’Loughlin 2004], also referred to
as anteroposterior deformation [Anton et al., 1992].
Such fronto-occipital reshaping compresses the
cranial vault along the anteroposterior axis, resulting
in expansion of the lambdoid sutures and widening
of the mediolateral axis [Cheverud et al., 1992], with
the most extreme cranial deformation resulting in
more severe brachycephaly (Fig. 1). The degree of
brachycephaly was determined by using calipers
to measure the biparietal diameter to the nearest
millimeter, dividing it by the anteroposterior diam-
eter, and multiplying by 100% (termed the cephalic
index (CI)).
The measure of the CI was assessed for correlation
with the number of wormian bones in skulls with
varying degrees of brachycephalic cranial deforma-
tion. The CI was also grouped into three categories:
normal (CI < 81), brachycephaly (CI 81–93), and
severe brachycephaly (CI > 93). These categories
were compared with the total number of wormian
bones found in each skull.

Diagnosis
Acrogeria
Aminopterin, prenatal
Camptodactyly syndrome,
Guadalajara Type I
Cerebellotrigeminal dermal
dysplasia
Chondrodysplasia punctata
(Conradi–Hunermann)
Cleidocranial dysostosis
Down syndrome
Multiple epiphysieal dysplasia,
with early-onset diabetes
mellitus
Geroderma osteodysplastica
Grant syndrome
Hajdu-Cheney syndrome
Hallermann Streiff (Progeroid
syndrome)
Hydrocephalus (isolated)
Hypophosphatasia
Hypothyroidism
Infantile multisystem
inflammatory disease (cinca)
Lateral meningocele syndrome
Mandibuloacral dysplasia
Menkes disease
Metaphyseal chondrodysplasia,
Jansen type
Mohr syndrome
Osteogenesis imperfectas
Oto-palato-digital syndrome,
Type II
American Journal of Medical Genetics Part A: DOI 10.1002/ajmg.a
THE MORPHOGENESIS OF WORMIAN BONES 3245
TABLE I. Differential Diagnoses of Wormian Bones*
Prominent features Locus/gene Causation omim#
Delayed fontanel closure, short stature, alopecia, Unknown AR (201200)
premature aging, deficient adipose tissue,
prominent vessels, acroosteolysis
Microcephaly, cranial dysplasia, cleft palate, None Prenatal drug exposure
mesomelia, hypodactyly
Intrauterine growth retardation, camptodactyly Unknown AR (211910)
thoracic, and spine abnormalities
Rare neurocutaneous syndrome of Unknown Isolated/sporadic (2601853)
craniosynostosis, ataxia, trigeminal
anesthesia, scalp alopecia, cerebellar
anomaly, midface hypoplasia, corneal
opacities, mental retardation, and short
stature.
Skin and hair defects, cataracts, and skeletal Xp11.23 (EBP) XLR (302960)
abnormalities including short stature,
rhizomelic shortening of the limbs, epiphyseal
stippling
Brachycephaly, late fontanel closure, wide 6p21 (CBFA1) AD (119600)
sutures, flat midface, hypoplastic clavicles,
short ribs
Hypotonia, mental retardation, characteristic Trisomy 21 AD (190685)
facies with specific major congenital
malformations of the heart and GI tract
Infancy-onset diabetes mellitus and multiple 2p12 (EIF2AK3) AR (226980)
epiphyseal dysplasia. Wolcott–Rallison
Syndrome
Skin changes with precocious aging and osseous Unknown AR (231070)
changes including osteoporosis and multiple
lines like growth rings of trees
Brachycephaly, delayed fontanel closure, Unknown AD (138930))
micrognathia, blue sclerae, joint laxity
Platybasia, delayed fontanel closure, wide Unknown AD (102500))
sutures, short stature, oligodontia, vertebral
anomalies
Microphthalmia, small pinched nose, Unknown AR (264090)
hypotrichosis
Hydrocephalus Variable Variable
Poorly mineralized cranium, short ribs, 1p36.1-34 (ALPL) AR (241500)
hypoplastic fragile bones
Coarse facies, slow growth, umbilical hernia, Variable Variable
slow development, enlarged posterior
fontanelle
Chronic meningitis, migratory skin rash, joint 1q44 (CIAS1) AD (607115)
inflammation, progressive visual defect,
perceptive deafness
Short stature, generalized osteosclerosis, Unknown AD (130720)
distinctive craniofacial features, multiple
thoracic and lateral meningoceles, and
enlarged sella turcica
Large fontanelle, wide cranial sutures, beaked 1q21.2 (LMNA) AR (248370)
nose, micrognathia, dental anomalies, skin
atrophy
Brain atrophy, brittle and kinky hair, dry skin, Xq12-q13 (Cu2þ XLR (309400)
seizures, mental retardation transporting) AtPase,
or polypeptide
Severe postnatal short stature, brachycephaly, 3p22 (PTHR) AD (156400)
metaphyseal disorganization with bowing
long bones, short distal phylanges
Orofaciodigital syndrome II; poly-, syn-, and Unknown AR (252100)
brachydactyly, lobate tongue with papilliform
protuberances, supernumerary skull sutures,
hearing loss, and frequent tachypnea
Blue sclerae, numerous fractures, hearing loss 17q21.31-q22 (COL1A1) AD (166200-40) (259400-20)
or 7q22.1 (COL1A2)
Sclerosis of skull, wide sutures, hypertelorism, Xq28 (FLNA) XLR (304120)
micrognathia, skeletal anomalies, syndactyly,
polydactyly
(Continued )
 American Journal of Medical Genetics Part A: DOI 10.1002/ajmg.a

3246 SANCHEZ-LARA ET AL.

TABLE I. (Continued )

Diagnosis Prominent features Locus/gene Causation omim#

Prader–Willi syndrome Muscular hypotonia, obesity, mental retardation, 15q12 (loss of paternal AD (176270)
short stature, hypogonadotropic imprinting)
hypogonadism, small hands, and feet
Progeria Alopecia, atrophy of subcutaneous fat, skeletal 1q21.2 (LMNA) AD (176670)
hypoplasia and dysplasia, premature aging
Pycnodysostosis Large fontanel, wide sutures, beaked nose, 1q21 (cathepsinK) AR (265800)
micrognathia, hepatosplenomegaly, multiple
fractures
Ritscher–Schinzel syndrome Dandy–Walker-like malformation with Unknown AR (220210)
atrioventricular septal defect, growth, and
mental retardation
Roberts-SC phocomelia Hypomelia, midfacial defect, severe growth Unknown AR (269000)
deficiency
Schnizel–Giedion Sclerosis of skull, wide sutures, limb anomalies, Unknown AR (269150)
hypertrichosis-midface mental retardation
retraction
Sclerosteosis Overgrowth with cortical hyperostosis and 17q12 (SOST) AR (269500)
syndactyly
Spondyloepimetaphyseal Short stature, abnormal face, brachydactyly, Unknown XLR (300232)
dysplasia, X-linked, with epimetaphyseal changes with spine
mental deterioration involvement and progressive mental
retardation
Stratton–Parker syndrome Growth hormone deficiency, dextrocardia, Unknown Unknown (185120)
brachycamptodactyly
Zellweger syndrome High forehead, macrocephaly, wide fontanelle, Several loci peroxisomal AR (214100)
hypotonia, mental retardation, liver disease, defect
and stippled epiphyses
*Adapted and expanded Table from Table 7–9 from ‘‘Human Malformations and Related Anomalies’’ second edition. Diagnoses were identified in the OMIM and Taybi
and Lachman Gamuts search engines using the search term ‘‘wormian.’’

FIG. 1. Examples of control skulls (A–C) beside purposefully deformed skulls from Ancon, Peru (D,E) and Chichen Itza, Mexico (G–I). Ordered from left to right as
side, top and back. Purposefully deformed skulls D, E and F are Peabody Number 73-6-30/7174.0 and G, H, and I are Peabody Number 07-7-20/N255.0.
 American Journal of Medical Genetics Part A: DOI 10.1002/ajmg.a

THE MORPHOGENESIS OF WORMIAN BONES 3247

Our second aim was to assess the impact of
craniosynostosis on wormian bones (Fig. 2). The
3-dimentional computerized tomography (3D-CT)
scans of non-syndromic, single-suture craniosynos-
tosis cases were obtained from five large craniofacial
centers throughout the USA. Because of possible
inter-rater reliability and variability in the resolution
of 3D-CT scans, we limited our analysis to only large
wormian bones (
1 cm) occurring within cranial
sutures and fontanelles. We used the same classi-
fication of wormian bone locations that was
described by O’Loughlin [2004]. The frequency and
location of wormian bones found in 3D-CT scans
were tabulated from 119 cases of sagittal synostosis,
41 cases of metopic synostosis, 37 cases of unilateral
coronal synostosis, and 10 cases of unilateral lamb-
doid synostosis. These data were compared with
wormian bone counts in anatomically normal skulls
from a 1905 manuscript by Parker. Parker counted,
measured, and grouped the wormian bones found in
these 485 normal adult human skulls of both sexes
and from several races (‘‘Auvergnats, Parisians, Neo-
Caledonians, Negros, and Incas’’). He categorized
the size of each wormian bone using five categorical
designations by size, with the upper two categories
accounting for all wormian bones measuring equal
to or greater than 1 cm. Category 4 comprised all
those bones which measured from 1 to 2 cm, in their
smallest diameter, and category 5 was any bone
measuring over 2 cm. Aside from the posterior
fontanelle (which appears to be included as part
of the posterior sagittal suture), the location of
the wormian bones in the Parker article correlated
well with those used in our 3D-CT scan assessment.
The data analysis for this paper was generated
using STATA software, StataCorp. 2005. Stata Stat-
istical Software: Release 9. College Station, TX:
StataCorp LP.
RESULTS
Skull Deformation
In the dry skull deformational study, we assessed
whether we could combine the data from the two
pre-Columbian tribes, by testing for a difference in
the CI using a Wilcoxon two sample test. Results
showed that the cephalic indices were not different
by tribe (Chi-squared ¼ 1.556 with 1 d.f. P ¼ 0.2123).
Regarding the absolute number of wormian bones,
there was a difference detected between the two
tribes (Chi-squared ¼ 4.166 with 1 d.f. P ¼ 0.0412).
When testing for differences between the combined
cases (pre-Columbian skulls) and controls (adult dry
skulls), these two groups were significantly different,
for both the CI (Chi-squared ¼ 26.554 with 1 d.f.
P ¼ 0.0001) and total wormian bones (chi-squared ¼
11.160 with 1 d.f. P ¼ 0.0008). When testing for a
correlation between the absolute number of wor-
mian bones and the raw CI we found no statistically
significant trend. When the CI was grouped into
three categories: (normal CI < 81, mild-moderate
brachycephaly 81 < CI < 93, and severe brachyce-
phaly CI > 94) there was a trend toward an increased
number of wormian as the severity of brachycephaly
increased (P ¼ 0.039) (Fig. 3).
Craniosynostosis
In assessing the role of craniosynostosis on the
formation of wormian bones, we compared the
location of large wormian bones (
1 cm) seen on

FIG. 2. Images from 3D-CT Scans. (A) Control lateral view, (B) Control top view, (C) Sagittal synostosis with a wormian bone (WB) in the anterior fontanel (AF) (top
view facing top of page). (D) Sagittal synostosis with a posterior fontanelle (PF) WB, (E) Left lambdoid synostosis with contralateral Lambdoid WB, (F) Metopic
synostosis with both an AF and PF WB, (G/H) (Two views of one case)—left coronal synostosis with multiple PF WBs, (I/J) (Two views of one case)—metopic
craniosynostosis with a PF WB.
 American Journal of Medical Genetics Part A: DOI 10.1002/ajmg.a

3248 SANCHEZ-LARA ET AL.

FIG. 3. Total number of wormian bones by cephalic index range.

3D-CT scans with data from anatomically normal
skulls. Out of the 207 scans with craniosynostosis,
43% (90/207) had at least one large wormian bone.
There was one scan with five large wormian bones,
three scans with four large wormian bones, 33 with
two, and 42 scans with one. Our analysis compared
the number of scans with one or more large wormian
bones with the number of large wormian bones
from the Parker article. We also grouped the location
of wormian bones into skull regions and compared
our results with that of Parker [1905]. The skull
regions were as follows: Central: Anterior Fonta-
nelle, Metopic Suture, Posterior Fontanelle, Sagittal
Suture; Back lateral: Lambdoid Suture; Middle side:
Squamosal Suture, Sphenoparietal Suture; Far Back-
Lateral: Asterion; and Front Lateral: Pterion. Here we
found a statistically significant difference in all areas
except in the front and back lateral sides (Pterion and
Lambdoid sutures) (Table II). Finally we tabulated
the wormian bones by region and stratified this data
by the region of craniosynostosis. Here, we found
that the type of craniosynostosis was associated
with an increased number of wormian bones in
certain skull locations. Midline synostosis, specifi-
cally metopic or sagittal synostosis had more
wormian bones in the midline, whereas unilateral
lambdoidal or coronal synostosis more often had
wormian bones on the contralateral side (Fig. 4).
DISCUSSION
Wormian bones are accessory cranial bones that
form from independent ossification centers within
sutures and fontanelles. Their growth is similar to that
of other cranial bones and initiates in the center of the
bone with radiation toward the periphery. They are
found in roughly 8–15% of the general population
and are more common in individuals of Chinese
descent. Males are more often affected than females,
and wormian bones are more often located on the
right side [Jeanty et al., 2000]. They appear most
frequently in lambdoid sutures, followed by coronal,
sagittal, and metopic sutures with 93% of all wormian
bones occurring in sutures bordering the parietal
bones. Their frequency within fontanelles is in the
following order of occurrence: asterion, posterior,
anterior, and orbital fontanelle.

TABLE II. Wormian Bones Found in Each Cranial Region: A Comparison of Craniosynostosis 3DCT Scans* With WB Totals in Non-Deformed
Skulls

3DCTs 3DCTs Parker skulls Parker skulls Odds ratio

with WBs without WB with WB without Wb (95% confidence Interval) P-value

Central (AF, MS, PF, SS) 55 152 6 479 OR 28.9 (12.07–83.29) <0.0001
Back lateral (LS) 25 182 80 405 OR 0.695 (0.41–1.14) 0.1380
Middle-Side (SqS Sph-Par) 16 191 5 480 OR 8.0 (2.76–28.37) <0.0001
Back Far-Lateral (Ast) 17 189 20 465 OR 2.1 (1.00–4.30) 0.0274
Front Lateral (Pter) 3 204 20 465 OR 0.34 (0.06–1.17) 0.1025
TOTAL WB 117 90 131 354 OR 3.51 (2.46–5.01) <0.0001
AF, anterior fontanelle; Ast, asterion; LS, lambdoid suture; MS, metopic suture; PF, posterior fontanelle; Pter, pterion; SS, sagittal suture; Sph-Par, sphenoparietal suture;
SqS, squamosal suture; WB, Wormian bones.
*With at least 1 Wormian bone (>1 cm).
 American Journal of Medical Genetics Part A: DOI 10.1002/ajmg.a
THE MORPHOGENESIS OF WORMIAN BONES
FIG. 4. Craniosynostosis patients with one or more wormian bones (WB). Count is separated by skull region and general area of craniosynostosis.
We were interested in determining what factors
influenced the frequency and location of wormian
bones. Through review of the early literature, Parker
[1905] tabulated a number of factors from anthro-
pological studies that influenced the number of
wormian bones. These included: cranial volume
[Chambellan, 1883], cranial deformation [Dorsey and
Holmes, 1897], and craniosynostosis [Parker, 1905].
In general, higher cranial volumes were associated
with increased numbers of wormian bones, with
more wormian bones noted in hydrocephalic skulls
(11.9 per skull with average cranial volume of 3,727
cc), versus normal skulls (5.9 per skull with average
cranial volume 1511 cc), versus microcephalic skulls
(3.7 per skull with average cranial volume 1100 cc),
versus anthropoid apes (1.0 per skull with average
cranial volume 433 cc). The size of wormian bones
ranged from 0.1 cm to greater than 2 cm, with smaller
wormian bones (<1 cm) being several fold more
frequent. In one large study of 1620 skulls from
Central and Southern Italy, there was no apparent
correlation between the size of lambdoid wormian
bones the CI or cranial capacity [Rubini, 1998].
In anthropologic studies on purposeful cranial
deformation, circumferentially deformed crania had
fewer wormian bones than undeformed skulls, and
skulls with anteroposterior deformation had the
most wormian bones [Anton et al., 1992]. In annular
deformation, the skull was tightly bound with cloth,
producing a conical shape, and this practice was
common in highland Peru [Dingwall, 1931]. Ante-
roposterior deformation between two boards (such
as was practiced by Northwest Pacific Coast Native
Americans) flattened areas in contact with the boards
and produced spreading and tension across the
adjacent sutures. Anton et al., [1992] hypothesized
that such circumferential deformation placed com-
pressional forces on the sutures resulting in fewer
3249
wormian bones, while anteroposterior deformation
increased tension across the sutures, thereby increas-
ing the number of wormian bones. In circumferential
deformation, growth is directed toward the vertex
and parallel to the sagittal suture, and the skull shape
mimics that of extreme vertex birth molding [Graham
and Kumar, 2006].
In our study, we examined brachycephalic skulls
from the Mayan and Ancon cultures. In Chichen Itza
Mexico, a classic Mayan culture that lived from A.D.
1200–1500, anteroposterior deformation was prac-
ticed. The cranial vault modification practiced by
pre-Columbian Ancon populations located along the
northern Peruvian coast during the Middle Horizon
(Huari Empire lasting from A.D. 600–1450) was
accomplished by wearing bandages around the
head to secure a headdress [Allison et al., 1981;
Cheverud et al., 1992]. It resulted in a cascade of
developmental effects on the growing cranial base
and face, resulting in a wider cranial base and a
foreshortened, wider face [Cheverud et al., 1992].
O’Loughlin [2004] noted that both annular and
parallelo-frontal occipital deformation placed com-
pression across the occipito-mastoid sutures, result-
ing in fewer asterionic wormian bones. In contrast,
occipital deformation does not directly compress the
lambdoid sutures and may actually spread them
apart, resulting in more lambdoid wormian bones.
In comparison to undeformed crania, both cultural
anterior–posterior cranial deformation and sagittal
craniosynostosis increased lambdoid wormian
bones, while fronto-vertico-occipital deformation
and sagittal craniosynostosis decreased anteriorly
placed wormian bones [O’Loughlin, 2004]. It was
also demonstrated that the frequency and location of
wormian bones varies depending on the type and
degree of cranial deformation. A positive correlation
between the frequency of lambdoid wormian bones
 American Journal of Medical Genetics Part A: DOI 10.1002/ajmg.a
3250 SANCHEZ-LARA ET AL.
and degree of deformation helped to confirm that
wormian bones form in relation to pressure across
the lambdoid sutures [O’Loughlin, 2004].
The varied locations of synostosis initiation sites
can influence cranial remodeling and growth forces.
In sagittal synostosis, posteriorly directed growth
results in greater forces across the apical (posterior)
fontanelle and lambdoid sutures. Similarly, with
unilateral lambdoid synostosis, the pressures differ
between the two asterionic fontanelles. When
sagittal synostosis is initiated in its usual location
between the parietal eminences in the posterior half
of the sagittal suture, more pressure is directed
posteriorly than when sagittal synostosis is initiated
in a more anterior location, possibly explaining why
wormian bones occur much more frequently in the
apical fontanelle than the anterior fontanel.
In our study, we noted increased numbers of
wormian bones in craniosynostosis, purposeful
cranial deformation, and in various disorders
which result in deformational brachycephaly due to
decreased mineralization or decreased movement.
Yet it is not clear exactly why wormian bones form
in these situations. It seems counter-intuitive to
develop wormian bones in situations with decreased
calvarial mineralization, as well as when there is
regionally increased bone formation in craniosynos-
tosis, yet in reviewing the spectrum of syndromes
with associated wormian bones (Table I), a unifying
feature for many of these conditions is early skull
deformation and often positional brachycephaly.
The underlying signals that trigger new ossification
centers and wormian bone formation in open sutures
are not clear because increased sutural width is
correlated with increased dural strain.
Unossified dura alone is not likely to be the signal,
since the anterior fontanelle is a rare site for wormian
bone formation in most syndromes, yet anterior
fontanelle wormian bones were seen in some cases
of sagittal synostosis. An interesting example of
nature is cleidocranial dysplasia caused by a com-
plete haploinsufficiency of RUNX2. [Cunningham
et al., 2006] These children are born with near
absence of ossified cranial bone. In the child
described by Cunningham in 2006, after external
cranial support was provided via a cranial orthotic
device, the entire skull ossified via wormian bone
formation, rather than through extension from
previously formed calvarial plates of bone. Orthotic
molding prevented deformational brachycephaly,
and a network of wormian bones formed throughout
the skull rather than from the normal bone ossifica-
tion centers with extension toward the sutures.
In this study, we found that regional wormian
bones typically form posteriorly with deformational
brachycephayly and are also related to the site
of initiation of non-syndromic craniosynostosis.
Because of the paucity of data available on our con-
trol populations, we were not able to match our
analysis by age or gender. It is possible that wormian
bones in adult skulls may have coalesced with
neighboring calvaria, and thus possibly underesti-
mating the number of wormian bones. Despite this
limitation, on a case only analysis of craniosynos-
tosis, we demonstrated a correlation of specific
suture synostosis with the location of wormian
bones. Specifically, we noted that the intracranial
pressure from the rapidly growing brain opens the
contralateral side. Sutural widening and dural strain
may be enough to trigger the formation of wormian
bones in these contralateral sutures with unilateral
lambdoid or coronal craniosynostosis. With sagittal
or metopic synostosis, these forces may be directed
anteriorly or posteriorly along the midline, increas-
ing wormian bone formation in midline fontanelles.
These factors suggest that mechanical forces play a
major role in the formation and localization of
wormian bones.
ACKNOWLEDGMENTS
We thank Dr. Dan Lieberman and Michele Morgan
of the Peabody Museum of Archaeology and
Ethnology at Harvard University for the opportunity
to examine their collection of purposefully deformed
skulls as well as Prof. G.E. Kennedy, Curator of the
Osteological Collection, Dept. of Anthropology,
UCLA, for her assistance in providing control skulls
for our review. We appreciate contribution sup-
ported by the NIH/NICHD Grant for Neurocognitive
Outcomes in Craniosynostosis (R01- DE 13813), and
we appreciate radiographic contributions from
colleagues at the Children’s Memorial Hospital
affiliated with Northwestern University, Children’s
at Scottish Rite-Atlanta, St. Louis Children’s Hospital,
Children’s Hospital of Los Angeles and the Children’s
Hospital of Philadelphia. This study was also
supported by NIH Skeletal Dysplasia Program
Project NICHD Grant (HD22657-11) and Medical
Genetics NIH/NIGMS Training Program Grant
(GM08243), as well as SHAREs Childhood Disability
Center (JMG).
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