Introduction
Background
Craniosynostosis is the premature fusion of the cranial sutures. Craniosynostosis can occur as an isolated defect or as part of a syndrome and is recognized in 2 forms: simple and compound. In simple craniosynostosis, only 1 cranial suture is involved; compound craniosynostosis (seen in the image below) involves 2 or more sutures.1,2
Three-dimensional CT scan demonstrates combined coronal and sagittal synostosis. Vertex view shows a normal lambdoid suture with complete fusion of the sagittal and coronal sutures.
Recent studies
Danelson et al investigated the possible benefits of employing 3-dimensional (3D) models in preoperative planning for craniosynostosis surgery, specifically, spring-mediated cranioplasty and cranial vault reconstruction.3 Models were created using image analysis software to isolate cranial vault bones from preoperative computed tomography (CT) scans of the study's patients; this information was ultimately fed into a 3D printer, which built a reproduction of each patient's cranial vault. The models were particularly useful as templates for prebending the springs used in spring cranioplasty and permitted better quantification of the springs' force characteristics.
In a retrospective study, Florisson et al investigated the rate of papilledema in patients with isolated craniosynostosis.4 Among the study's 205 children, each with an isolated, single-suture craniosynostosis, 14 developed papilledema before or after surgery. The papilledema group was made up of 9.7% of patients with dolichocephaly (also called scaphocephaly) and 5.6% of children with trigonocephaly. (See Clinical Details for a discussion of these conditions.) Based on these results, the authors recommended that patients with trigonocephaly or dolichocephaly (particularly those with the latter condition) receive routine preoperative screening for papilledema. They also recommended postoperative screening for patients if papilledema is at all a possibility.
Pathophysiology
In the literature, mutations have been reported in gene coding for fibroblast growth factor receptors (FGFRs) in affected families with craniosynostosis. The receptors mediate the effects of the fibroblast growth factors that modulate cellular processes, such as growth, differentiation, migration, and survival. Mutations of the FGFR2 gene, located on chromosome 7, have been recognized in Crouzon disease and in Apert, Jackson-Weiss, and Pfeiffer syndromes. Some cases of Pfeiffer syndrome and Crouzon disease involve mutations of both the FGFR1 and FGFR3 genes. These mutations account for a small fraction of cases of craniosynostosis; most cases have an unclear etiology.5
With the use of immunocytochemistry techniques, abnormal osteoblastic activity has been observed within the synostotic bone, along with decreased growth rate and alkaline phosphatase production. Histopathologic examinations of resected sutures have demonstrated new bone formation at various stages. These stages range from trabecular interdigitation across the fibrous tissue to complete bony fusion.
Frequency
United States
The estimated incidence of simple or compound craniosynostosis is approximately 1 case per 2000 live births. Approximately 80-90% of cases involve isolated defects, while the remaining cases are part of a recognized syndrome. In the isolated cases, the sagittal suture is affected most often, followed by the coronal, lambdoid, and metopic sutures.
Mortality/Morbidity
In most patients with craniosynostosis involving a single suture, the primary concern is cosmetic. Early diagnosis and surgical therapy are essential to prevent lifelong craniofacial deformity. Patients with diffuse craniosynostosis are at risk of developing increased intracranial pressure (ICP). Patients can have airway problems because of a hypoplastic maxilla, or ophthalmologic problems related to shallow orbits. Patients with Apert, Pfeiffer, or Carpenter syndromes also have significant surgical issues related to fusion anomalies of the digits, such as that in the image below.
Abnormal soft-tissue and bony fusion of the toes in a patient with Apert syndrome.
Race
No racial predilection exists.
Sex
Several forms of craniosynostosis have sex predilections. A slight male predominance is observed in cases of sagittal synostosis, and a female predominance is noted in cases of coronal synostosis.
Age
Most cases are evident during the neonatal period.
Anatomy
The bones of the cranium (frontal, parietal, temporal, and occipital) are well developed by the fifth month of gestation. The membranous skull bones are joined by connective tissue at the sagittal, coronal, metopic, lambdoid, and squamous sutures. The anterior fontanelle is at the junction of the frontal and parietal bones, and it represents the intersection of the metopic, coronal, and sagittal sutures. It normally closes in children by the age of 20 months. The posterior fontanelle, located at the junction of the lambdoid and sagittal sutures, closes by the age of 3 months. Mature suture closure occurs by the age of 12 years, but completion of fusion continues into the third decade of life and beyond.
Presentation
Skull growth is restricted in the plane perpendicular to the prematurely fused suture and enhanced in the plane parallel to it. Synostosis of the sagittal suture (seen in the images below) produces a long and narrow skull, called scaphocephaly or dolichocephaly. The anteroposterior diameter of the skull is increased, whereas the transverse diameter is decreased. Sagittal synostosis is most commonly seen in men. Although the biparietal diameter is low, the actual head volume is normal; therefore, no increase in ICP, no hydrocephalus, and no neurologic deficits are usually present.6,7,8,9
Sagittal synostosis. The anteroposterior (AP) diameter of the head is markedly increased (dolichocephaly), with flattening of the superior contour noted. The sagittal suture is fused, with widening of both the coronal suture and lambdoid suture.
Three-dimensional computed tomography (CT) scan viewed from the top shows complete fusion of the sagittal suture, with a patent coronal suture and an elongated cranial contour. Apparent holes in the posterior parietal regions are due to normal thinning.
Synostosis of the coronal suture can occur bilaterally (brachycephaly) or unilaterally (plagiocephaly). Brachycephaly results in the short, wide skull demonstrated in the images below, with a shortened anteroposterior diameter and a flattened occiput and forehead. Brachycephaly is seen more commonly in females and is associated with a higher incidence of neurologic complications, including increased ICP, optic atrophy, and mental retardation, than sagittal synostosis, which is usually associated with normal intellectual function.
Coronal synostosis. The AP diameter of the head is shortened (brachycephaly), with partially fused coronal sutures and a widened sagittal suture. Note the bilateral harlequin configuration of the orbits (see also the slitlike appearance of the coronal suture in the image below).
Coronal synostosis. The AP diameter of the head is shortened (brachycephaly), with partially fused coronal sutures and a widened sagittal suture (same patient as in the above image). Note the bilateral harlequin configuration of the orbits and the slitlike appearance of the coronal suture (arrow). The margins of the coronal suture are densely sclerotic as well.
Three-dimensional CT scan shows brachycephaly. The AP diameter is shortened, with completely fused coronal sutures and open lambdoid sutures.
A higher incidence of anomalies is also associated with coronal craniosynostosis: in plagiocephaly (shown below), the incidence rate is 33%; in brachycephaly, the incidence can be as high as 59%.
Combined synostosis also demonstrating plagiocephaly. AP view in a newborn with combined fusion of the sagittal and coronal sutures. Note the sclerotic margins and heaped-up bone of the fusing sagittal suture, the flattening of the right side of the calvaria (plagiocephaly), and the right harlequin orbit.
Combined synostosis also demonstrating plagiocephaly (same patient as in the above image). Lateral view in a newborn with combined fusion of the sagittal and coronal sutures. The right coronal suture is abnormally straight (large arrow) and narrow in appearance, whereas the left suture is normal (small arrow).
Synostosis of the lambdoid sutures is less common than sagittal and coronal synostosis. A marked flattening and underdevelopment of the posterior fossa are present with lambdoid synostosis, and overgrowth of the bregma may occur, resulting in a tall cranial shape called oxycephalic or turricephalic skull.
Synostosis of the metopic suture, which occurs in utero, is rare. Called trigonocephaly, it results in a pointed forehead (shown in the image below) and hypotelorism, with an increased risk for associated anomalies of the forebrain. Other anomalies often encountered with metopic synostosis include cleft palate, coloboma, and a wide array of urinary tract abnormalities.
Trigonocephaly. Oblique view of the skull shows a ridge or keel in the midline of the frontal bone due to early fusion of the metopic suture (arrow).
A combined synostosis of the coronal and sagittal sutures results in a severe form of craniosynostosis termed oxycephaly, which can lead to microcephaly. In addition, increased ICP is associated with significant neurologic complications.
The most severe form of craniosynostosis is called the kleeblattschãdel deformity, or cloverleaf skull, in which the coronal, sagittal, and lambdoid sutures are all affected. The skull resembles a cloverleaf shape, and patients typically have a bulging forehead, proptotic eyes, and severe neurologic impairment.
The most common syndrome-associated synostoses are Crouzon disease and Chotzen and Apert syndromes, which account for more than two thirds of syndrome-related craniosynostosis.
- Asymmetric craniosynostosis and plagiocephaly characterize Chotzen syndrome, which is inherited as an autosomal dominant trait and is associated with facial asymmetry, ptosis of the eyelids, shortened fingers, a low frontal hairline, a long pointed nose, and soft-tissue syndactyly. Cervical fusion is often seen at the level of the C2-3 vertebrae.
- Crouzon disease is inherited as an autosomal dominant trait in 75% of patients. The remaining 25% of cases are sporadic. The skull shape (seen below) varies depending on the order of fusion, but brachycephaly is the most common result due to closure of the coronal and basal skull sutures. Associated findings include ocular proptosis, maxillary hypoplasia, parrot-beak nose, and ocular hypertelorism with normal limbs. Hydrocephalus is more common in Crouzon disease than in the other syndromes, and chronic tonsillar herniation is a common MRI finding in patients with Crouzon disease.
Crouzon disease. Note the abnormal shape of the head, with premature fusion of the sagittal suture and hypoplastic maxilla, which is severely disproportionate to the normal mandible.
Crouzon disease. Patient had an abnormal shape of the head with premature fusion of the sagittal suture and hypoplastic maxilla (same patient as in the above image). Clinically, the patient had severe proptosis due to underdeveloped orbits.
- Apert syndrome (acrocephalosyndactyly), seen in the image below, is an autosomal dominant disorder characterized by coronal synostosis in conjunction with a malformed and short cranial base.8 It is associated with extensive syndactyly of the second, third, and fourth fingers (mitten hands); broad thumbs with radial deviation; toe syndactyly (sock toes); and visual impairment. Patients with Apert syndrome have an increased risk of mental retardation; 50% of patients have an intelligence quotient lower than 70. Cervical vertebrae fusion, primarily at the C5-6 vertebrae, occurs in 68% of patients.
Apert syndrome. Markedly deformed tower-shaped head resulting from the premature fusion of all cranial sutures. Patient also had syndactyly, mitten hands, and sock feet.
- Carpenter syndrome is inherited as a rare autosomal recessive trait and usually results in the kleeblattschãdel deformity.9 Soft-tissue syndactyly is always present in the hands and feet. Mental retardation is common.
- Pfeiffer syndrome is autosomal dominant and differs from Apert syndrome by the presence of polydactyly. Pfeiffer syndrome is categorized into 3 types, with varying deformities.
- Type I is the most common form and often results in moderate-to-severe hearing loss. Abnormalities found on CT scans include auditory canal stenosis or atresia and either hypoplasia or enlargement of the middle ear cavity. Type I is associated with broad thumbs and toes with variable syndactyly. The eyes often are spaced widely apart and prominent.
- Type II is characterized by a cloverleaf skull, severe proptosis, and ankylosis of the elbows.
- In addition to manifesting bilateral craniosynostosis and ocular proptosis, patients with type III Pfeiffer syndrome may present with developmental delays, hydrocephalus, hearing defects, and short stature. Fusion of the cervical spine, a cone-shaped epiphysis, and hypoplastic bones about the elbow are additional features.
- Jackson-Weiss syndrome has been mapped to the same gene as Crouzon disease. Both coronal and basal skull synostoses are present. Associated findings include enlarged great toes and craniofacial abnormalities similar to those found in Pfeiffer syndrome but without thumb abnormalities.
- Each syndrome has an increased risk of elevated ICP, hydrocephalus, optic atrophy, respiratory problems due to a deviated septum, and disorders of speech and hearing. Surgical intervention results in an improved cosmetic appearance along with a substantially decreased risk of neurologic complications.
Increased ICP is frequently caused by abnormalities of cerebral venous drainage as a result of maldevelopment of the foramina at the skull base.
Preferred Examination
Patients in whom craniosynostosis is suggested should undergo a careful clinical examination, with the clinician looking for abnormalities of the skull and extremities.
Plain radiography is the first radiologic step. Plain radiography quickly and simply identifies skull-shape abnormalities, which are seen in most patients with craniosynostosis. With this simple and inexpensive examination, usually all cranial sutures can be surveyed for patency. Conventional cranial CT scans with bone windows or 3D CT scans are frequently obtained to confirm bony abnormalities and to delineate any associated intracranial anomalies. Three-dimensional CT is the criterion standard for the evaluation of craniosynostosis.
Limitations of Techniques
The entire length of each suture is not always visible on plain radiographs, and some patients have only a small bony bar limiting growth at a particular suture. If the skull shape is entirely normal, craniosynostosis is unlikely.
CT is considered expensive and may require that the patient be sedated.
Differential Diagnoses
Other Problems to Be Considered
The conditions listed below are associated with secondary synostosis:
Metabolic conditions leading to premature fusion
Hyperthyroidism
Hypophosphatasia
Hypercalcemia
Vitamin D deficiency
Hurler syndrome
Positional molding
Retarded brain growth as a primary abnormality
Severe constraint in utero
More on Craniosynostosis |
 Overview: Craniosynostosis |
| Imaging: Craniosynostosis |
| Follow-up: Craniosynostosis |
| Multimedia: Craniosynostosis |
| References |
| Further Reading |
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References
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Danelson KA, Gordon ES, David LR, Stitzel JD. Using a three dimensional model of the pediatric skull for pre-operative planning in the treatment of craniosynostosis - biomed 2009. Biomed Sci Instrum. 2009;45:358-63. [Medline].
Florisson JM, van Veelen ML, Bannink N, et al. Papilledema in isolated single-suture craniosynostosis: prevalence and predictive factors. J Craniofac Surg. Jan 12 2010;[Medline].
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Mitsukawa N, Satoh K, Hayashi T, Furukawa Y, Suse T, Uemura T, et al. Sinus pericranii associated with craniosynostosis. J Craniofac Surg. Jan 2007;18(1):78-84. [Medline].
Martelli H Jr, Paranaíba LM, de Miranda RT, Orsi J Jr, Coletta RD. Apert syndrome: report of a case with emphasis on craniofacial and genetic features. Pediatr Dent. Nov-Dec 2008;30(6):464-8. [Medline].
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Ploplys EA, Hopper RA, Muzaffar AR, Starr JR, Avellino AM, Cunningham ML, et al. Comparison of computed tomographic imaging measurements with clinical findings in children with unilateral lambdoid synostosis. Plast Reconstr Surg. Jan 2009;123(1):300-9. [Medline].
Krakow D, Santulli T, Platt LD. Use of three-dimensional ultrasonography in differentiating craniosynostosis from severe fetal molding. J Ultrasound Med. Apr 2001;20(4):427-31. [Medline].
Behrman RE, Kuelman R, Jenson H. Craniosynostosis. In: Kliegman R. Nelson Textbook of Pediatrics. 16th. Philadelphia, Pa: WB Saunders Co; 2000:1831-2.
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Further Reading
Related eMedicine topics
Craniosynostosis (from Neurology)
Craniosynostosis (from Neurosurgery)
Craniosynostosis Management
Crouzon Syndrome
Apert Syndrome
Clinical studies
Amicar Pharmacokinetics of Children Having Craniofacial Surgery
Clinical Study of Muenke Syndrome (FGFR3-Related Craniosynostosis)
Osteogenic Profiling of Tissue From Children With Craniosynostosis
Tranexamic Acid for Craniofacial Surgery
Keywords
craniosynostosis, craniosynostosis surgery, plagiocephaly, synostosis, Apert syndrome, sagittal synostosis, dolichocephalic, dolichocephaly, scaphocephaly, trigonocephaly, Crouzon syndrome, brachycephaly, Chotzen syndrome, cranial sutures, cranial synostosis, metopic synostosis, oxycephaly
