eMedicine Specialties > Radiology > Pediatrics
Craniosynostosis
Updated: Jun 1, 2007
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 involves 2 or more sutures.
Pathophysiology
In the recent 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.1
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.
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 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.
Synostosis of the coronal suture can occur bilaterally (brachycephaly) or unilaterally (plagiocephaly). Brachycephaly results in a short, wide skull, 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. A higher incidence of anomalies is also associated with coronal craniosynostosis: in plagiocephaly, the incidence rate is 33%; in brachycephaly, the incidence can be as high as 59%.
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 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.
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 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.
- Apert syndrome (acrocephalosyndactyly) is an autosomal dominant disorder characterized by coronal synostosis in conjunction with a malformed and short cranial base. 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.
- Carpenter syndrome is inherited as a rare autosomal recessive trait and usually results in the kleeblattschãdel deformity. 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 3-dimensional (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
Radiography
Findings
Plain radiographs are obtained easily and demonstrate osseous anatomy well. At a minimum, views should include anteroposterior (AP), Townes, and bilateral lateral films. Plain radiographs are useful for identifying the abnormalities of head shape (dolichocephaly, brachycephaly, and plagiocephaly) that are characteristic of the various forms of craniosynostosis.
Plain radiographs can be used for the following:
- Identifying prematurely fused sutures (Normal sutures are seen on plain images as serrated, nonlinear, lucent lines. Sutures in patients with craniosynostosis are usually straight with sclerotic heaped-up margins or are completely absent. The sclerotic margins may outline the sutures well and lead to the false impression that they are patent. Particular attention should be paid to the presence of this sclerotic margin and to focal sites of heaped-up margins, which are indicative of premature synostosis.)
- Demonstrating overall morphology of the cranium
- Identifying the presence of localized problems (constricting bony bands restricting growth)
- Identifying the presence of generalized problems (copper-beaten appearance, indicating elevated ICP)
- Identifying other skeletal anomalies
Degree of Confidence
Visualizing the length of all sutures is not always possible, and suture closure may be difficult to detect unless it is accompanied by an abnormal head shape.
False Positives/Negatives
Normal variations in the shape of the pediatric skull exist. For example, many formerly premature infants have long, narrow skulls resembling dolichocephaly but without sagittal synostosis. Many children also have asymmetric flattening of the occiput caused by habitually lying on 1 side of the head, without underlying suture abnormalities; this is called positional molding. These 2 types of skull deformities are more common than craniosynostosis.
Computed Tomography
Findings
CT scans provide a more detailed method for visualizing intracranial pathology and detailed anatomy of the calvaria and brain parenchyma. In contrast to plain radiographs, the skull base is visualized well, and hard and soft tissues of the craniofacial skeleton can be studied in detail.
- Neuroimaging is performed in children with isolated suture synostosis primarily to look for underlying brain damage or associated cerebral anomalies.
- Infants with trigonocephaly may have midline anomalies (eg, holoprosencephaly).
- Anomalies of the venous drainage and stenosis of the venous foramina at the skull base can occur with multisuture synostosis with both syndrome- and nonsyndrome-related causes.
- After abnormal or suggestive plain radiographic findings are noted, CT scans with bone windows with or without 3D reconstruction are frequently requested prior to surgical therapy.
- Features such as shallow anterior fossa, deformed dystopic orbits, abnormal calvarial contour, and asymmetric cranial base can be realistically depicted.
Degree of Confidence
The sensitivity of CT scans, when combined with physical examination and plain radiography, approaches 100%.
False Positives/Negatives
Even on CT scans, the entire length of every suture may not be clearly visible. Once again, normal variations in skull shape may pose a problem.
Magnetic Resonance Imaging
Findings
MRI shows better definition of intracranial soft-tissue structures than CT. In addition, MRI is useful in the detection of hydrocephalus and cerebral developmental defects, such as myelination defects and deformities of the maxilla resulting in airway compromise.
If children with craniosynostosis have abnormalities of tone or have diminished movements, MRI should be performed because it is the most sensitive method for detecting both cortical and white matter abnormalities.
False Positives/Negatives
MRI is not a strong modality for evaluating bony abnormalities and thus cannot be used as the primary method of evaluating craniosynostosis. MRI is used primarily for assessing associated brainstem and soft tissue abnormalities.
Ultrasonography
Findings
The recent literature has shown some advancement in the prenatal detection of craniosynostosis by using 3D versus 2D ultrasonography. A case was reported by Krakow et al in which prenatal 2D ultrasonographic findings were consistent with craniosynostosis.2 After 3D ultrasonography, positional molding was suspected instead. Neonatal radiographs confirmed that the case was that of positional molding.
With 3D ultrasonography, the full length of the suture is visible, which is not possible with conventional ultrasonography. Ultrasonography can also be useful in detecting bony abnormalities associated with the syndrome-related causes of craniosynostosis.
Degree of Confidence
Research is ongoing to determine the usefulness of ultrasonography as a tool in diagnosing craniosynostosis.
False Positives/Negatives
Ultrasonography is user dependent, and therefore, inexperienced personnel can miss the diagnosis of craniosynostosis.
Intervention
Medicolegal Pitfalls
- Results are best when surgery is performed in young infants.
- A delayed diagnosis can lead to medical/legal liability.
Multimedia
Media file 1: 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.
Media file 2: 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.
Media file 3: 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 Image 4).
Media file 4: 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 Image 3). 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.
Media file 5: Three-dimensional CT scan shows brachycephaly. The AP diameter is shortened, with completely fused coronal sutures and open lambdoid sutures.
Media file 6: 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).
Media file 7: 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 (see also Image 8).
Media file 8: Combined synostosis also demonstrating plagiocephaly (same patient as in Image 7). 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).
Media file 9: 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.
Media file 10: Apert syndrome. Markedly deformed tower-shaped head resulting from the premature fusion of all cranial sutures (same patient as in Image 11). Patient also had syndactyly, mitten hands, and sock feet.
Media file 11: Apert syndrome. Markedly deformed tower-shaped head resulting from the premature fusion of all cranial sutures (same patient as in Image 10). Patient also had syndactyly, mitten hands, and sock feet. Note the abnormal soft-tissue and bony fusion of toes.
Media file 12: 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 (same patient as in Image 13).
Media file 13: Crouzon disease. Patient had an abnormal shape of the head with premature fusion of the sagittal suture and hypoplastic maxilla (same patient as in Image 12). Clinically, the patient had severe proptosis due to underdeveloped orbits.
References
Jabs EW. Toward understanding the pathogenesis of craniosynostosis through clinical and molecular correlates. Clin Genet. Feb 1998;53(2):79-86. [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.
Cohen MM Jr. Craniosynostosis update 1987. Am J Med Genet Suppl. 1988;4:99-148. [Medline].
Goetz C, Pappert E. Textbook of Clinical Neurology. Philadelphia, Pa: Harcourt Brace & Co; 1999:533-4.
Kapp-Simon KA, Speltz ML, Cunningham ML, Patel PK, Tomita T. Neurodevelopment of children with single suture craniosynostosis: a review. Childs Nerv Syst. Mar 2007;23(3):269-81. [Medline].
Lin H, Ruiz-Correa S, Shapiro LG, Hing A, Cunningham ML, Speltz M. Symbolic shape descriptors for classifying craniosynostosis deformations from skull imaging. Conf Proc IEEE Eng Med Biol Soc. 2005;6:6325-31. [Medline].
Merkes J, Sarnat H. Child Neurology. 6th. Philadelphia, Pa: Lippincott Williams & Wilkins; 2000:351-4.
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].
Rudolph A, Hoffman J, Rudolph C. Rudolph's Pediatrics. 20th. Stamford, Conn: Appleton & Lange; 1996:412-4.
Silverman FN, Caffey J, Kuhn JP. Mosby-Year Book. In: Essentials of Caffey's Pediatric X-Ray Diagnosis. Chicago, Ill: 1990:11-19.
Swaiman K, Ashwal S. Mosby-Year Book. In: Pediatric Neurology: Principles & Practice. 3rd. Philadelphia, Pa: 1999:276-84.
Keywords
premature fusion of cranial sutures, cranial sutures, simple craniosynostosis, compound craniosynostosis, cranial synostosis, synostosis, suture synostosis, sagittal synostosis, coronal synostosis, metopic synostosis, lambdoid synostosis, combined synostosis, scaphocephaly, dolichocephaly, brachycephaly, plagiocephaly, oxycephaly, trigonocephaly, kleeblattschädel deformity, Cloverleaf deformity, Crouzon disease, Chotzen syndrome, Apert syndrome
Contributor Information and Disclosures
Author
Majid A Khan, MD, Consulting Neuroradiologist, Department of Diagnostic Radiology, GV(Sonny) Montgomery VA Medical Center
Majid A Khan, MD is a member of the following medical societies: American College of Radiology and American Society of Neuroradiology
Disclosure: Nothing to disclose.
Coauthor(s)
David I Weltman, MD, Consulting Staff, S & D Medical, LLP; Director, Department of Radiology, Southside Hospital
David I Weltman, MD is a member of the following medical societies: American College of Radiology, American Roentgen Ray Society, Association of Program Directors in Radiology, New York County Medical Society, and Radiological Society of North America
Disclosure: Nothing to disclose.
Brian J Webber, DO, Staff Physician, Department of Radiology, Nassau University Medical Center
Brian J Webber, DO is a member of the following medical societies: American Medical Student Association/Foundation and American Osteopathic Association
Disclosure: Nothing to disclose.
Dvorah Balsam, MD, Chief, Division of Pediatric Radiology, Nassau University Medical Center; Professor, Department of Clinical Radiology, State University of New York at Stony Brook
Disclosure: Nothing to disclose.
Medical Editor
Charles M Glasier, MD, Professor, Departments of Radiology and Pediatrics, University of Arkansas for Medical Sciences; Chief, Magnetic Resonance Imaging, Vice-Chief, Pediatric Radiology, Arkansas Children's Hospital
Charles M Glasier, MD is a member of the following medical societies: American College of Radiology and American Institute of Ultrasound in Medicine
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Pharmacy Editor
Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
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Managing Editor
Marta Hernanz-Schulman, MD, FAAP, Professor, Radiology, Radiological Sciences, and Pediatrics, Director, Department of Pediatric Radiology, Radiologist-in-Chief, Director, Department of Diagnostic Imaging, Vanderbilt University Medical Center, Vanderbilt Children's Hospital
Marta Hernanz-Schulman, MD, FAAP is a member of the following medical societies: American Institute of Ultrasound in Medicine and American Roentgen Ray Society
Disclosure: Nothing to disclose.
CME Editor
Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute
Robert M Krasny, MD is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America
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Chief Editor
Eugene C Lin, MD, Consulting Staff, Department of Radiology, Virginia Mason Medical Center
Eugene C Lin, MD is a member of the following medical societies: American College of Nuclear Medicine, American College of Radiology, Radiological Society of North America, and Society of Nuclear Medicine
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