Women’s Health Alliance,Department of Ultrasound,300 20th Avenue North, Nashville, TN 37203-2131.

This article was originally published in the Journal of Ultrasound in Medicine

Abstract: The prenatal diagnosis of wormian bones has not been made previously. We report four fetuses with wormian bones but with none of the associated anomalies. The diagnosis, differential diagnosis, associated anomalies and prognosis are discussed.

Introduction: Wormian bones are small irregular ossicles located within the cranial sutures (most often in the lambdoid sutures) and fontanelles. The first description of intrasutural bones is attributed to Paracelsus (1460 – 1541 CA ) ¹, however, the name “wormian bones” is derived from Olaus Worm, a Danish anatomist who described them in a letter to Thomas Bartholin in 1643. ^1,2,3

A large body of literature has described various associations between wormian bones and congenital anomalies. Although the mechanisms responsible for the formation of wormian bones are unknown, some studies have shown that their presence may serve as a marker for the identification of anomalies of the central nervous system. ³ When wormian bones occur as a normal variant, they tend to be smaller and less numerous than when they are associated with skeletal dysplasias. ⁴ Since, to the best of our knowledge, the prenatal diagnosis of wormian bones has not been made, we report the prenatal ultrasound diagnosis of wormian bones in four fetuses.

Case report:
Patient # 1:The patient is a 20-year-old G1,P0. The ultrasound examination at 21weeks demonstrated choroid plexus cysts and two wormian bones in the posterior fontanelle (fig. 1). An amniocentesis demonstrated a normal male karyotype. The rest of the pregnancy was unremarkable. An uneventful vaginal delivery resulted in a 3950g normal child with Apgar of 9/9. The child is now 7 years old and is developing normally.

Tangential view of the posterior fontanelle at 21 weeks. The fetal face is looking down to the left and behind the image, the occipital bone occupies the lower right quadrant:

Patient #2 : The patient is a 27-year old G1,P0 with unremarkable family and personal history. Her routine ultrasound examination was performed at 17 weeks, 3 days and was unremarkable, aside from the presence of 2 wormian bones in the posterior fontanelle (fig. 2) and a questionably elevated first toe in one of the feet. The male baby was spontaneously delivered at 38 weeks gestation and weighed 3435g. The neonatal course was unremarkable and no anomalies were detected in the child. At 4 years, the child's development is normal.

Tangential view of the posterior fontanelle at 17 weeks. The fetal face is looking straight back behind the image. Note the well-formed and symmetrical shape of both wormian bones.

Patient #3: The patient is a 22-year old G1,P0 with unremarkable family (aside from a cousin born with cataract) and personal history. Her routine ultrasound examination was performed at 19 weeks 6 days and was unremarkable, aside from the presence of 3 small wormian bones in the posterior fontanelle (fig. 3). A normal female baby was spontaneously delivered at term and weighed 3400g. The neonatal course was unremarkable and no anomalies were detected in the child. At 2 years, the child's development is normal.

Three small wormian bones in a 19-week fetus:

Patient #4: The patient is a 32-year old G2,P1 with unremarkable family and personal history. Her routine ultrasound examination was performed at 18 weeks 5 days and was unremarkable, aside from the presence of 2 wormian bones in the posterior fontanelle (fig. 4) and an unfilled bladder (normal on a subsequent scan). A normal male baby was spontaneously delivered at term and weighed 3287g. The neonatal course was unremarkable and no anomalies were detected in the child. At 1 month, the child's development is normal.

Two very large wormian bones in a 18 week fetus:

Discussion
Historical perspective: The terminology of "wormian bones†is derived from a 1643 description of the intersutural bones by Olaus Worm to Thomas Bartholin .¹ However, wormian bones had been described in the past with the first description attributed to Paracelsus (1460 to 1541 CA). ^2,3 Wormian bones have been recognized in an Australopithecine skull. In the 16th century, the anatomists Andernach and Vesale were the first to associate wormian bones with cerebral disorders. ^2,3 The fascination with the study of the skull during the past century has resulted in many studies and reports describing associated diseases and hypothetical etiologies.^3,5,6,7,8,9 

Nomenclature : In his monograph, Parker ² mentioned several synonyms that were used according to:
•The discoverer: ossicula Andernaci, ossa Goethiano.
•The shape: ossa triquetra, ossa triangularis, ossa quadratum.
•The localization: suturaux, fontanellaires, insules, intercalaria, raphogeminantia, apicis.
•The function: complementaria, ossa accessorii.
Nowadays, wormian bones are also called ossa Wormiana, Intersutural bones and Inca bones.

Incidence: As expected, the incidence of wormian bones has varied with the bias of the reporting authors. In 1963, Brothwell studied the incidence in different populations, and his data is reproduced in table I.¹⁰ El-Najjar suggested that the incidence is lower in fetuses (11.3%) than in adults (62.1% - 76.2%). ⁶ However, he compared skulls from a group of contemporary fetuses with skulls that came from a group of adult prehistoric Indians. In 1979, Pryles, studying groups of children in hospitals and schools, showed that the incidence of wormian bones in humans varies from 8% to 15% in a random population and reaches 54% in a mentally impaired population. ³  These series dealt with relatively small numbers, and the incidence of 14% found in a series of 1010 skulls by Parker ¹ seems more in accordance with the clinical experience of reviewing skull films in general radiology. All the studies concluded that there is no difference between sexes.

Embryology: Since wormian bones belong to the neurocranium, they share its embryology. They appear as isolate ectopic islands of intramembraneous ossifications. In the fetus, the diploë is not formed yet, and thus wormian bones are composed of a single layer of compact bone on the dural side. ⁴

Etio-pathogenesis: Wormian bones can be found as normal variants and seem to be determined genetically in certain populations. ⁴ However, as expected for a topic that has been studied for so many years, many etiologies have been proposed, but none is universally accepted. Some of the etiologies include:
1. Racial feature of Native American Indian populations.  
This alleged etiology illustrates the longevity of some erroneous medical theory, even when they have long been disproved. The original description of wormian bones as a characteristic of the Inca population comes from an 1851 book "Peruvian Antiquities†by Rivero, Edwards and von Tsudi. They wrote:  "…it may be proper to notice an osteologic anomaly, very interesting, which is observed in the crania of all three races (Chincas, Aymares, Huancas) and it is this; that those children of tender years…present an interparietal bone…It follows that this interparietal bone occupies precisely that part of the occiput which in the other crania is occupied by the upper portion of the occipital, and which is connected with the parietals by the lambdoid suture. At four or five months this bone is regularly united to the occipital. It is a circumstance worthy of learned anthropologists, that there is thus found in one section of the human race a perpetual anomalous phenomenon, which is wanting in all others, but which is characteristic of the ruminant and carnivorous animalsâ€. This association was disproved as early as 1865, but the name of  "Inca†bones still persists.

2. Consequence of skull deformation.  
In 1897, Dorsey suggested that wormian bones developed as a response to the stressful conditions of artificial cranial deformations, from the Native American practice of carrying newborns on cradleboards (a hard board onto which the newborn was bundled and carried on the mother's back). ^{13, 14} In 1965, Bennett suggested that wormian bones were a response to modification of the shape of the head (artificial deformation, short basi-occiput length, or pathological conditions such as hydrocephaly). ⁵ However, El-Najjar, in 1977 comparing the incidence of wormian bones in deformed and undeformed skulls of Southwestern Indians, concluded that there is no significant difference between these two groups.⁹ He proposed that artificial cranial deformation does not influence the incidence of wormian bones but affects the number of these bones when they are present. ⁹

3.An adaptation to cranial enlargement.
Parker suggested that: "the number of wormian bones increases with the capacity of the skull, regardless of the cause of enlargementâ€. His data is based on various skulls from normal populations, and from abnormal skulls (microcephalic having fewer, and hydrocephalic—at a time when shunting did not exist—having more) ². A similar relationship exists with the total length of sutures: "The greater the sutural length of a skull the greater the number of wormian bonesâ€. He suggests that sutural diastasis induces the formation of ectopic ossification centers.

4. Metabolic disorders. 
In 1946, Hess proposed that the formation of wormian bones could result from metabolic disorders of the mesoderm, and also correlated to asymmetry of the skull, bone malformations (occiput, sphenoid), metopism, and congenital anomalies of the central nervous system. ¹⁵

5.An autosomal dominant trait.
Torgerson proposed in three different studies (1951 /1952 / 1954), that wormian bones are inherited as a dominant trait with incomplete penetrance (50%) and variable expression. In 1977, El-Najjar suggested that the presence of wormian bones in fetuses is related to a genetic component on their formation but did not elaborate further.⁶

Location: About half of the wormian bones are located in the lambdoid suture and fontanelle (and the masto-occipital suture). The second most common occurrence (about 25%) is in the coronal suture. The rest occur in any remaining sutures and fontanelles ⁷.

Diagnosis: In the current four cases, obtaining a tangential section of the skull at the level of the posterior fontanelle made the diagnosis. Wormian bones appeared as well - delineated islands of tissue with bone echogenicity inside the fontanelle. The edge of the bone is still as smooth as other fetal cranial bones and does not present with the serpiginous appearance of the adult bones.

Differential diagnosis: Craniosynostosis presents as a narrowing of the sutures and fontanelles. Usually by the time they are recognized prenatally, they are associated with bulging of other parts of the skull with such deformities as cloverleaf - shaped skull. Craniosynostosis can also be distinguished by the fact that the suture is narrowed (or not visible at all), while in the four cases of wormian bones, the bones clearly presented as an island of tissue in the intersutural space. Another potential differential diagnosis is a partial wormian bone (a "peninsular†formation) in which the wormian is partially attached (or separated) from a normal cranial bone by an incomplete suture.

Associated anomalies: Many diseases have been associated with wormian bones. The most commonly described condition associated with this entity is disorders of the central nervous system. According to Pryles, the prevalence of central nervous system abnormalities in a population with wormian bones varies from 93% to100% in a random group, and reaches 100% in a mentally retarded population. ³ In the same study, other associated anomalies included low set auricles, congenital tracheomalacia, single umbilical artery and congenital heart disease. Other authors have not validated these high percentages. Other reported associations can be found in Table II.

Prognosis: The wormian bones, in themselves, do not carry a pejorative prognosis, and thus the prognosis will depend on the type and severity of the associated diseases.

Management: A careful search for other abnormalities should be made. When wormian bones are found isolated, standard obstetrical management is not altered.
 
Table 1.
Percentage of wormian bones in different populations according to Brothwell ¹⁷

Population	Incidence
Chinese	80.32%
German	75.00%
Australian	72.58%
Iron/Age Romano-British	71.03%
Melanesian	64.15%
Lachish	63.41%
Anglo-Saxon	55.56%

Normal variants Acrogeria Aminopterin fetopathy Aplasia cutis congenita Chondrodysplasia punctata disease Cleidocranial dysplasia Congenital cutis laxa19 Congenital heart disease3 Congenital tracheomalacia3 Copper deficiency Craniostenosis3 Dysgenesis of the corpus callosum Grant syndrome Hajdu-Cheney syndrome Hallerman-Streiff syndrome Hydrocephalus Hypophosphatasia Hypothyroidism Idiopathic familial osteoarthopathy Infantile multisystem inflammatory disease

Kinky hair syndrome20 Low set auricles3 Macrocephaly3 Mandibuloacral dysplasia Menkes syndrome Metaphyseal Chondrodysplasia (Jansen) Microcephaly3 Osteogenesis imperfecta Osteopterosis (infantile type) Oto-palato-digital syndrome Pachydermoperostosis Prader-Willi syndrome Progeria Pyknodysostosis20 Rickets20 Schinzel-Giedion syndrome Sclerosteosis Single umbilical artery3 Trisomy 21 Zellweger syndrome

Modified and adapted from Kaplan ⁴, Pryles ³, Kozlowski ¹⁸, Biver ¹⁹, Reeder ²⁰

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