Craniosynostosis is a congenital abnormality of the central nervous system that involves the premature closing of one or more of the fibrous joints between the bones of the skull (cranial sutures).
Description
Craniosynostosis is a birth defect that affects the shape of the skull. Individuals born with craniosynostosis have abnormally shaped heads and a prominent bony ridge over the affected suture or sutures. All affected individuals also are likely to experience water on the brain (hydrocephalus) that can cause enlargement of the head and increased pressure inside the skull. Developmental delay is commonly experienced by those individuals affected by craniosynostosis.
There are two major classifications of craniosynostosis: primary and secondary. There are multiple causes
of primary craniosynostosis, which involves abnormal cranial suture development. The premature closure of one or more of the sutures causes the skull bones to grow parallel to the affected suture but not perpendicular to it. At other sutures there may be too much growth. The disrupted growth patterns cause a misshapen skull. The cause of secondary craniosynostosis is failure of the brain to grow and expand. This results in uniform premature suture closure, so that the head is symmetric and abnormally small (microcephalic).
The human skull consists of several bony plates separated by a narrow gap that contains stem cells. These fibrous joints are referred to as cranial sutures. There are six cranial sutures: the sagittal, which runs from front to back across the top of the head; the two coronal sutures, which run across the skull parallel to and just above the hairline; the metopic, which runs from front to back in front of the sagittal suture; and the two lambdoid sutures, which run side to side across the back of the head. There are seven types of primary craniosynostosis divided by the cranial suture or sutures that are affected: sagittal, bicoronal (both coronal sutures), unicoronal (one coronal suture), coronal and sagittal, metopic, lambdoid and sagittal, and total, in which all the cranial sutures are affected. Approximately 40% of all cases of craniosynostosis are sagittal, 20% are bicoronal, 15% are unicoronal, 10% are coronal and sagittal, 4% are metopic, 1% are lambdoid and sagittal, and 10% are total.
Genetic profile
Craniosynostosis does not have a single genetic cause, but it has been demonstrated to have a genetic component in that it is sometimes passed from one generation to another. It has been associated with over 150 different genetic syndromes. Genetic inheritance of craniosynostosis is not sex-linked (it is autosomal), and has been tied to both dominant and recessive traits. The overall occurrence rates are equivalent between males and females, but sagittal craniosynostosis is seen four times as often in males as in females, while coronal craniosynostosis is observed twice as often in females as in males.
As of 1997, 64 distinct mutations in six different genes have been linked to craniosynostosis. Three of these genes, at chromosome locations 8p11, 10q26, and 4p16, are related to fibroblast growth factor receptors (FGFRs), which are molecules that control cell growth. Other implicated genes are the TWIST gene (7p21), the MSX2 gene (5q34-35), and the FBN1 gene (15q21.1).
Not all instances of craniosynostosis appear to have a genetic origin. The most common cause of non-genetic craniosynostosis is constraint of the fetal head during pregnancy. This is believed to account for between 50 and 60% of all cases of craniosynostosis.
Known genetic syndromes account for another 10 to 20% of the cases of craniosynostosis. These syndromes include Muenke syndrome,Apert syndrome, Pfeiffer syndrome, Carpenter syndrome, and Crouzon syndrome, among others.
Demographics
Craniosynostosis has an incidence of approximately one in every 2,000 live births. Genetic-based craniosynostosis is most commonly a dominant trait, but in some cases has also been shown to be recessive. Therefore, while it is more likely to occur in children with a family history of craniosynostosis, it may not occur in the children of such families and it may also occur in children with no family history of the disorder. Non-genetic craniosynostosis has a higher occurrence among the children of malnourished or drug-abusing mothers. It is also more likely to occur in the children of teenage mothers because of the lack of development of an appropriately sized uterus for fetal growth in many of these cases.
Signs and symptoms
The most obvious symptom of craniosynostosis is an abnormally shaped head that is not the result of the birth process. Craniosynostosis may be confirmed by the presence of a bony ridge over the affected cranial suture. Associated symptoms include unusual facial features such as wide-set, down-slanting, or protruding eyes and a prominent jaw; visual impairment; hearing loss; breathing problems; water on the brain (hydrocephalus); and developmental delay.
Each type of craniosynostosis has different physically observable symptoms and results in a different head shape. Sagittal craniosynostosis is characterized by a long and narrow skull (scaphocephaly). This is referred to as an increase in the A-P, or anterior-to-posterior, diameter. Thus, looking down on the top of the skull, the diameter of the head is greater than normal in the front-to-back direction. Individuals born with sagittal craniosynostosis have broad foreheads and a larger than normal back of the head. The so-called soft spot found just beyond the hairline in a normal baby (the anterior fontanelle) is missing or very small in a baby affected with sagittal craniosynostosis. The result of neurological testing is generally normal for individuals with sagittal craniosynostosis.
Bicoronal craniosynostosis is characterized by a wide and short skull (brachycephaly) or by a cloverleafshaped skull. This is referred to as a decrease in the A-P
diameter. Individuals affected with bicoronal craniosynostosis have poorly formed eye sockets and fore-heads. This causes a lower than normal sized eye-socket which can cause complications of vision. These complications include damage to the optical nerve which can cause a loss of visual clarity; bulging eyeballs (a condition called proptosis) that usually results in damage to the cornea; widely spaced eyes; and, a narrowing of the sinuses and tear ducts that can cause inflammation of the mucous membranes that line the exposed portion of the eyeball (conjunctivitis). Bicoronal craniosynostosis can be further complicated by water on the brain (hydrocephalus) and increased intracranial pressure. Most individuals affected with bicoronal craniosynostosis also have an abnormally high and arched palate that can cause dental problems and protrusion of the lower jaw. Bicoronal craniosynostosis is associated with the Acrocephalosyndactyly syndromes (genetic syndromes that involve abnormalities of the head and webbed fingers or toes), which include Apert syndrome, Apert-Crouzon syndrome, Chotzen syndrome, and Pfeiffer syndrome.
Unicoronal craniosynostosis is characterized by a skull that is more developed in the front on one side than it is on the other side (frontal plagiocephaly). This leads to a distinct asymmetry between the sides of the face, a flattening of the forehead on the side affected by the premature suture closure, and a misalignment of the eyes such that the eye on the affected side is higher than the eye on the unaffected side.
Coronal and sagittal craniosynostosis is characterized by a cone-shaped head (acrocephaly). The front soft-spot (the anterior fontanelle) is generally much larger than normal and it may never close without surgical intervention. Individuals affected with coronal and sagittal craniosynostosis may have higher than normal intracranial pressure. Pfeiffer syndrome is closely associated with coronal and sagittal craniosynostosis.
Total craniosynostosis is characterized by a normally shaped but small skull (microcephaly). Individuals affected with total craniosynostosis have higher than normal intracranial pressures and they are the most likely of all craniosynostosis affected individuals to suffer from developmental delay.
Metopic craniosynostosis is characterized by a triangular shaped forehead (trigonocephaly) and thickened bones in the forehead and narrowly spaced eyes. Individuals affected with metopic craniosynostosis tend to have developmental abnormalities associated with processes that are known to be controlled by the front of the brain (the forebrain). Lambdoid and sagittal craniosynostosis is the most rare type of craniosynostosis. It is characterized by a flattening of the back of the skull (the occipital bone) and a bulging of the front of the skull (the frontal bone). This condition may occur symmetrically or asymmetrically.
Diagnosis
Prenatal, transabdominal, or traditional ultrasound is generally used to assess fetal skull development in the second and third trimesters of pregnancy. As of 2000, the
resolution of such images is not always clear enough for a confident diagnosis of craniosynostosis. A transvaginal ultrasonic test to detect skull abnormalities in fetuses has been conducted in Japan and it offers much higher image clarity, allowing for the direct observation of cranial suture development as early as the second trimester, particularly of the sagittal and coronal sutures. Bicoronal and unicoronal craniosynostosis associated with one of the acrocephalosyndactyly syndromes may be detected via two different genetic tests now available that are able to identify the underlying mutations in the FGFR or TWIST genes. The sensitivity of this test is very high for certain genetic syndromes associated with coronal craniosynostosis: 100% for Muenke syndrome and 98% for Apert syndrome.
Almost all cases of craniosynostosis are evident at birth; however, the cranial sutures are not fully closed at this time so instances of craniosynostosis have been diagnosed later in infancy as well. Skull x rays and/or a CT scan may also be used after birth to diagnose craniosynostosis.
Treatment and management
Since craniosynostosis is associated with other conditions and may require multiple treatments of the skull, face, eyes, and ears, a multidisciplinary team of doctors and specialists is often required. The skull abnormalities of craniosynostosis should be surgically corrected within the first year of life. In the first year of life, changing the elevation and contours of the skull bones is much easier and new bone growth and reshaping occur rapidly. Also, at this point, the facial features are still highly undeveloped, so significant improvement in appearance can be achieved. Multiple surgeries may be required over the patient's lifetime, depending on the circumstances of the case. Follow-up support by pediatric, psychological, neurological, surgical and genetic specialists may be necessary.
In the types of craniosynostosis that involve the eyes, consultation with an ophthalmologist is recommended and eye surgery may be necessary. Speech and hearing therapy may also be needed when the ears and the frontal lobe have been affected. In the case of bicoronal craniosynostosis where the palate is severely malformed, dental consultation may also be required. In the most severe cases of coronal craniosynostosis, it will be necessary to address feeding and respiratory problems that are associated with the abnormally formed palate and sinuses.
Families with a history of craniosynostosis can participate in genetic counseling in order to learn whether genetic testing can identify the likelihood that their children might be affected.
Prognosis
In all but the most severe and inoperable cases of craniosynostosis, it is possible that considerable improvement in physical appearance can be achieved via surgery. Depending on the neurological damage resulting from certain types of craniosynostosis versus the rapidity of treatment, certain affected individuals may suffer developmental disabilities ranging from the extremely mild to very severe. Most individuals with craniosynostosis that involves the coronal sutures will continue to have vision problems throughout life. These problems vary in severity and many are now amenable to fully corrective treatments.
PERIODICALS
Pooh, R., et al. "Transvaginal sonography of the fetal brain: Detection of abnormal morphology and circulation." Croatian Journal of Medicine (1998): 147-57.
Wilkie, A. "Craniosynostosis: genes and mechanisms." Human Molecular Genetics (1979): 1647-56.
ORGANIZATIONS
Children's Craniofacial Association. PO Box 280297, Dallas, TX 75243-4522. (972) 994-9902 or (800) 535-3643. contactcca@ccakids.com. <http://www.ccakids.com>.
Craniosynostosis and Parents Support. 2965-A Quarters, Quantico, VA 22134. (877) 686-CAPS or (703) 445-1078. <http://www.caps2000.org/>.
