Craniosynostosis
Craniosynostosis
Definition
Craniosynostosis is one of a diverse group of deformities in the head and facial bones called craniofacial anomalies. An infant or child with craniosynostosis has improperly fused or joined bones (sutures) in the skull. ("Cranio" means skull; "synostosis" means fused bones.) When children with craniosynostosis also show other body deformities, their condition is called syndromic craniosynostosis. Primary craniosynostosis occurs when one or more of an infant's sutures (where skull bones meet) fuse prematurely. Secondary craniosynostosis results when one or more of an infant's sutures fuse prematurely as a result of lack of proper brain growth.
Description
A baby's skull is often thought of as a single piece of bone. However, it is actually made up of several bones that fit together like a jigsaw puzzle. These areas meet at what are called sutures. Sutures allow a growing baby's brain to expand. The four sutures come together at the fontanel, or "soft spot" in a baby's head. Eventually the sutures stop growing, and the cranial bones fuse.
Sometimes a suture is fused too early, however, preventing a growing child's brain from expanding. This condition can cause the brain to grow more rapidly in another area of the skull. The result is an abnormally shaped skull. Sometimes this happens before birth (congenital), or sometimes it occurs as the baby develops after birth.
There are four sutures of the skull that may be affected by craniosynostosis:
- Metopic: This suture extends from the top of the head down the middle of the forehead to the nose.
- Coronal: This suture extends from each ear to the fontanelle.
- Sagittal: This suture extends from the front of the head to the back, down the middle of the top to the head.
- Lambdoidal: This suture extends across the back of the head.
Types
The form of craniosynostosis depends on the suture or sutures that are affected.
Plagiocephaly (unicoronal synostosis)
Plagiocephaly is the most common form of craniosynostosis. It occurs in approximately one out of every 2,500 births. Plagiocephaly involves early fusion of either the right or left side of the coronal suture, the suture that extends from each ear over the top of the head to the fontanelle. The forehead and brow of a child with plagiocephaly look as if they have been pushed back or flattened because the forehead and brow have stopped their normal growth.
Brachycephaly (bicoronal synostosis)
Brachycephaly, which means "short headed," occurs when the right and left coronal sutures close prematurely. Brachycephaly results in an abnormally broad head with a high forehead. It is often associated with other craniofacial abnormalities, including Crouzon syndrome, Apert syndrome, Pfeiffer syndrome, and Saethre-Chotzen syndrome. It also is associated with Down syndrome (trisomy 21).
Trigonocephaly
This type of craniosynostosis involves fusion of the metopic suture that runs from the top of the head toward the nose, which can create a ridge running down the forehead and gives the front of the head a wedge-shaped effect. The eyes also may be close together.
Scaphocephaly (sagittal craniosynostosis)
This early fusion involves the sagittal suture that runs from front to back on the top of the skull. The result can be a long, narrow skull.
Positional nonsyndromic plagiocephaly (positional molding)
Positional nonsyndromic plagiocephaly is a form of craniosynostosis. In 1992, the American Academy of Pediatrics recommended that infants sleep on their backs to reduce the risk of sudden infant death syndrome (SIDS). This successfully reduced the number of infants with SIDS, but also increased the number of infants suffering from positional plagiocephaly due to back sleeping. An infant with positional nonsyndromic plagiocephaly has a flattened skull at the back of the head. This condition is also commonly called positional molding or deformational plagiocephaly.
Demographics
Craniosynostosis occurs in one out of 2,000 live births in the United States. It affects males twice as often as females. Of those affected, 2–8 percent have primary craniosynostosis and the remaining cases are secondary craniosynostosis. Plagiocephaly is the most common form of craniosynostosis. It occurs in approximately one out of every 2,500 live births. Sagittal craniosynostosis is the most common type of single suture craniosynostosis. It is estimated to occur in one in 4,000 to 8,500 live births. Although sagittal craniosynostosis mostly occurs by chance, about 2–6 percent of cases are considered to be inherited.
Frequencies of the types of craniosynostosis based on suture classification include: sagittal (50–58%); coronal (20–29%); metopic (4–10%); and lambdoid (2–4%).
Causes and symptoms
As of 2004 the exact cause of craniosynostosis is not understood. Many scientists believe it is the result of a defect in the ossification (bone formation) in the bones of the skull. Craniosynostosis usually occurs by chance (sporadic). In some families, however, it is inherited.
Genetic abnormalities such as craniosynostosis are described by the type of chromosome that carries the abnormal gene and whether the gene is recessive or dominant. The autosomal chromosomes are the nonsex chromosomes.
Autosomal recessive
In order for a child to inherit an autosomal recessive abnormality, both parents have to be carriers of the abnormal gene. When both parents are carriers, there is a 25 percent chance that each child born will inherit the abnormal gene and develop craniosynostosis. The child also has a 50 percent chance of inheriting the abnormal gene and becoming a carrier. Males and females are affected equally.
Autosomal dominant
When one parent has the abnormal gene and the other parent has normal genes, craniosynostosis can still result. That is because the abnormal gene dominates the normal gene. For an autosomal dominant disorder when one parent is a carrier of the abnormal gene, there is a 50 percent chance each child born will inherit the abnormal gene. Males and females are affected equally.
Other genetic syndromes, such as Crouzon syndrome, Apert syndrome, and Pfeiffer syndrome, are associated with craniosynostosis. All have different patterns of inheritance and chances of recurrence.
The physical symptoms of craniosynostosis depend on the sutures affected. Since other syndromes are associated with craniosynostosis, other symptoms may also be present, including the following:
- Endocrine disorders: Hyperthyroidism (overactivity of the thyroid gland), vitamin D deficiency , renal osteodystrophy (defective bone development), hypercalcemia (high levels of calcium in the blood), and rickets (weakened bones resulting from vitamin D deficiency).
- Hematologic disorders: Bone marrow diseases including sickle cell disease, and thalassemia.
- Inadequate growth of brain: Microcephaly (abnormal smallness of head), and hydrocephalus (abnormal buildup of cerebrospinal fluid in the head).
When to call the doctor
Craniosynostosis is a progressive condition that must be treated. The skull and facial asymmetry associated with craniosynostosis are frequently observed by an infant's pediatrician or family physician. Parents may also observe the condition.
Diagnosis
Craniosynostosis may be present at birth or may be observed later when a child has delays in neurological development. It often may be diagnosed by physical examination alone. Craniosynostosis may be suspected when an infant has an abnormally shaped head or a small bony ridge along the skull in various locations. The condition may also be suspected if a baby's fontanel (soft spot) closes off earlier than expected. The physician will do a complete physical exam and take a complete prenatal and birth history of the child, including position in the uterus. Family history of craniosynostosis or other craniofacial abnormalities also will be discussed.
Since craniosynostosis may be associated with other neurological and muscular disorders, such as Crouzon syndrome, Apert syndrome, or Pfeiffer syndrome, the physician will also discuss whether there have been any delays in the child's developmental progression.
If craniosynostosis is suspected, an x ray or a CT scan of the child's skull will be taken. In addition, DNA testing can help identify the gene mutations that can cause the condition. Mutations in what are called fibroblast growth factor receptors (FGR1, 2, and 3) and the transcription factor TWIST are responsible for several types of craniosynostosis.
KEY TERMS
Anomaly —Something that is different from what is normal or expected. Also an unusual or irregular structure.
Apert syndrome —A craniofacial abnormality characterized by abnormal head shape, small upper jaw, and fusion of fingers and toes.
Asymmetrical —Unbalanced, disproportionate, or unequal.
Brachycephaly —An abnormal thickening and widening of the skull.
Chromosome —A microscopic thread-like structure found within each cell of the human body and consisting of a complex of proteins and DNA. Humans have 46 chromosomes arranged into 23 pairs. Chromosomes contain the genetic information necessary to direct the development and functioning of all cells and systems in the body. They pass on hereditary traits from parents to child (like eye color) and determine whether the child will be male or female.
Computed tomography (CT) —An imaging technique in which cross-sectional x rays of the body are compiled to create a three-dimensional image of the body's internal structures; also called computed axial tomography.
Coronal suture —Skull suture that lies behind the forehead area, across the head from left side to the right side.
Craniosynostosis —A premature closure of one or more of the joints (fissures) between the bones of the skull, which causes an abnormally shaped skull.
Crouzon syndrome —A disorder characterized by malformations of the skull and face.
Deformational plagiocephaly (positional molding) —A form of craniosynostosis in which the head is misshapen, the result of constant pressure to the same area of the head.
Fontanelle —One of several "soft spots" on the skull where the developing bones of the skull have yet to fuse.
Lambdoidal suture —The suture between the two parietal bones and the occipital bone in the skull.
Metopic suture —Suture extending from the top of the head down the middle of the forehead to the nose.
Pfeiffer syndrome —This condition includes craniosynostosis, shallow eye sockets, underdevelopment of the midface, short thumbs and big toes, and possible webbing of hands and feet.
Plagiocephaly —A form of craniosynostosis that involves fusion of the right or left side of coronal suture.
Sagittal suture —The suture between the two parietal bones in the top of the skull.
Scaphocephaly —An abnormally long and narrow skull.
Suture —A "seam" that joins two surfaces together, such as is found between the bones of the skull. Also refers to stitching together the torn or cut edges of tissue.
Trigonocephaly —An abnormal development of the skull characterized by a triangular shaped forehead.
Treatment
For most children with craniosynostosis, facial and skull deformity will be obvious and may be expected to worsen as the child grows. Surgical management by experienced neurosurgeons (brain surgeons) and orthopedic (bone) surgeons will be necessary in most cases. It usually is performed between the ages of six and ten months.
Surgery involves releasing the fused sutures and reshaping the bone of the skull and eye orbit. The fused sutures are excised (removed), and the skull reshaped and replaced with a variety of materials. Surgery usually lasts for three to seven hours, and several days of hospitalization are necessary to monitor and treat any complications of the surgery. When more severe deformities are present, repeat surgery of the skull and eye sockets may be necessary. This will help release and advance the child's mid-face.
In the early 2000s, newer, less invasive techniques are being developed using endoscopes. Endoscopes are narrow tubes that are inserted into the brain through narrow incisions (cuts). They allow surgeons to visualize the brain and pass tiny surgical instruments through the tube to perform surgery to re-open the sutures and allow the brain to grow normally.
Children born with co-existing craniofacial conditions, such as Apert syndrome, which affects the growth of the jaw, may benefit from a technique called mandibular bone lengthening or distraction osteogenesis. This technique was first used in Russia to treat bone problems in the leg and has now been used successfully to correct deformities of the jaw.
Positional plagiocephaly (positional molding, deformational plagiocephaly)
Positional plagiocephaly, the result of an infant's back sleeping position, can be treated by varying the infant's sleeping position from back to side sleeping, and providing tummy play time. A wedge-shaped foam pillow sold at many baby stores may help position the infant for side sleeping. The child may also be repositioned in the crib or the crib's location changed. When positional molding is identified at less than three months of age, repositioning is usually successful in stopping the plagiocephaly and reversing the flattening. If the flattening is severe or the condition is not caught until an infant is older, a helmet may be necessary. The helmet is specifically made for the infant by an orthotic specialist, a person who creates devices that provide more normal functioning for impaired people. The infant may wear the helmet for up to 23 hours daily, removing it only during baths. Average length of treatment is three to six months. The helmet gently redirects the skull's growth and is most successful when the skull is most pliable, from about three months to about six months. The plagiocephaly will be monitored throughout this time, and the helmet adjusted as the child grows.
Prognosis
It is important to detect and treat craniosynostosis early. Untreated craniosynostosis will remain the same or worsen as a child grows and can affect a child's mental and physical development. Associated neuromuscular conditions also may affect the child's development. A child with craniosynostosis will require ongoing medical evaluations to ensure that the brain, skull, and facial bones are developing properly.
Prevention
As of 2004 there was no known prevention for craniosynostosis. Nothing that parents did or did not do causes the condition. The exception is positional plagiocephaly, which results from an infant being put to sleep on the back. This can be prevented by varying the infant's sleeping position from back to side sleeping, and providing tummy play time. A wedge-shaped foam pillow sold at many baby stores may help position the infant for side sleeping.
Parents who have an increased likelihood of carrying the genes that result in craniosynostosis may seek genetic counseling to better understand inheritance patterns and chances for reoccurrence.
Parental concerns
The physical symptoms of an asymmetrical face and head seen when a child has craniosynostosis are readily apparent and may cause the child embarrassment. The pressure a growing brain exerts on a fused suture also can cause a delay in development or, rarely, permanent brain damage. In addition, several conditions exist along with craniosynostosis and need to be evaluated.
A child needs to be carefully evaluated when craniosynostosis is present to distinguish between positional plagiocephaly, caused by back sleeping, and other forms of craniosynostosis. Positional plagiocephaly can be treated by repositioning the infant and perhaps by having the infant wear a helmet. Craniosynostosis must be treated by surgery. The differential diagnosis and treatment of posterior plagiocephaly is a challenging aspect of craniofacial surgery.
Resources
PERIODICALS
Coumoul, Xavier, and Deng Chu-Xia. "Roles of FGF receptors in mammalian development and congenital diseases." Birth Defects Research Part C: Embryo Today: Reviews 69 (2003): 286–304.
Jimenez, David, et al. "Endoscopy-assisted wide-vertex craniectomy, barrel stave osteotomies, and postoperative helmet molding therapy in the management of sagittal suture craniosynostosis." Journal of Neurosurgery (Pediatrics 5) 100 (2002): 407–17.
Kabbani, H., and T. S. Raghuveer. "Craniosynostosis." American Family Physician 69 (June 15, 2004): 2863–70.
Panchal, Jayesh, and Venus Uttchin. "Management of Craniosynostosis." Plastic & Reconstructive Surgery 111 (May 2003): 2032–49.
ORGANIZATIONS
Crouzon Support Network. PO Box 1272, Edmonds, WA 98020. Web site: <www.crouzon.org/>.
FACES: The National Craniofacial Association. PO Box 11082, Chattanooga, TN 37401. Web site: <www.facescranio.org/>.
National Association for Rare Disorders. 55 Kenosia Avenue, PO Box 1968, Danbury, CT 06813–1968. Web site: <www.rarediseases.org/info/contact.html>.
WEB SITES
"Autosomal dominant." MedlinePlus, June 15, 2003. Available online at <www.nlm.nih.gov/medlineplus/ency/article/002049.htm> (accessed December 9, 2004).
"Autosomal recessive." MedlinePlus, June 15, 2003. Available online at <www.nlm.nih.gov/medlineplus/ency/article/002052.htm> (accessed December 9, 2004).
"Craniofacial Anomalies." The Children's Hospital of Philadelphia, 2002. Available online at <www.chop.edu/consumer/your_child/condition_section_index.jsp?id=-9703> (accessed December 9, 2004).
"Craniosynostosis: A new less, invasion treatment." Craniosynostosis Net, July 15, 2003. Available online at <www.craniosynostosis.net/about.html> (accessed December 9, 2004).
"NINDS Craniosynostosis Information Page." National Institute of Neurological Disorders and Stroke, 2004. Available online at <www.ninds.nih.gov/health_and_medical/disorders/craniosytosis_doc.htm> (accessed December 9, 2004)
Christine Kuehn Kelly
Craniosynostosis
Craniosynostosis
Definition
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.
Resources
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. [email protected]. <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/>.
WEBSITES
Craniosupport.<http://www.craniosupport.com/>.
Pediatric Database (PEDBASE) Homepage.<http://www.icondata.com/health/pedbase/files/CRANIOSY.HTM>.
Robin, N. "Craniosynostosis Syndromes (FGFR-Related)." GeneClinics.<http://www.geneclinics.org/profiles/craniosynostosis/details.html>.
Paul A. Johnson
Craniosynostosis
Craniosynostosis
Definition
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 over-all 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.
At least 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 foreheads. This causes a lower than normal sized eye-socket that 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), which 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 lining 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. 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 often recommended and eye surgery may also 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 coronal sutures will continue to have vision problems throughout life. These problems vary in severity and many are now amenable to fully corrective treatments.
Resources
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. [email protected]. <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/>.
WEBSITES
Craniosupport. <http://www.craniosupport.com/>.
Pediatric Database (PEDBASE) Homepage. <http://www.icondata.com/health/pedbase/files/CRANIOSY.HTM>.
Robin, N. "Craniosynostosis Syndromes (FGFR-Related)." GeneClinics. <http://www.geneclinics.org/profiles/craniosynostosis/details.html>.
Paul A. Johnson
Craniosynostosis
Craniosynostosis
Definition
Craniosynostosis is a defect in which one or more of the flexible and fibrous joints (cranial sutures) between the skull bones closes too soon; it occurs before birth or within a few months after birth. The skull cannot expand normally with growth of the brain, and so assumes an abnormal shape. Craniosynostosis can occur alone or as part of a syndrome of craniofacial defects.
Description
The skull of a newborn is composed of five bones that are held together by the fibrous sutures positioned at the front, top, sides, and back of the skull. By remaining open, the sutures allow the skull to normally expand in all directions as the brain is growing.
The premature closing of one or more of these cranial sutures stops the normal capacity of the skull to expand in early childhood. As not all of the cranial sutures will close, the skull expands in the areas that are still flexible. This results in an abnormally shaped skull or face. The forehead may be very pronounced and inclined forward. Viewed from above, the skull may be more rectangular in shape rather than oval.
Other forms of craniosynostosis include coronal craniosynostosis (affecting the coronal suture that crosses the top of the skull from temple to temple), metopic craniosynostosis (affecting the metopic suture of the forehead), sagittal craniosynostosis (affecting the sagittal suture that unites the two parietal bones), and lambdoidal craniosynostosis (affecting the lambdoid suture between the occipital and parietal bones of the skull).
Demographics
Craniosynostosis is a rare occurrence. The sagittal form of the disorder, in which the sagittal suture closes prematurely, is the most common form of craniosynostosis, occurring in three to five of every 1,000 babies, typically males. The frequencies of the various types of craniosynostosis are 50–60% sagittal, 20–30% coronal, 4–10% metopic, and 2–4% lambdoid.
Causes and symptoms
Craniosynostosis is usually caused by a genetic mutation. Mutations in several genes (designated TWIST, FGFR-1, FGFR-2, and FGFR-3) have been linked with craniosynostosis. In particular, the protein encoded for by TWIST is critical in the initiation and maintenance of the cranial suture process. As of 2004, the favored hypothesis is that the protein that normally functions to ensure that the formation of the cranial sutures occurs at the right time in development somehow goes awry and causes premature fusion of the bones of the brain.
Research published in 2003 in the Annals of the Royal College of Surgeons of England identified Saethre-Chotzen syndrome (a rare disorder characterized by an exaggerated forehead and drooping eyelids) as a genetic disorder that produces craniosynostosis.
Craniosynostosis can also be caused by maladies that affect the metabolism (rickets, vitamin D deficiency, overactive thyroid) and by bone marrow disorders. Furthermore, some cases have been associated with an abnormally small head (microcephaly ) and the accumulation of cerebrospinal fluid in the brain (hydrocephalus ).
Involvement of the different sutures produces different effects. Closure of the sagittal suture (located at the top of the skull and to the rear) produces an elongated head, prominent and protruding forehead, and narrow temples. Closure of the coronal suture (located on the side of the skull) produces a flattened forehead, higher-than-normal eye socket, abnormal nose, and a skull that slants from side to side. Closure of the metopic suture (which runs down the front-middle portion of the skull) results in a pointed-shaped forehead, triangular-shaped skull, closer-than-normal eyes, and a protruding rear portion of the skull. Finally, closure of the lambdoidal suture (located at the back of the skull) produces a mild flattening of the back of the head, forward-shifted ears, and the coronal symptoms.
Diagnosis
Diagnosis is made on the basis of a physical examination.
Treatment team
Treatment involves medical specialists (pediatric neurosurgeons, pediatric plastic surgeons, craniofacial surgeons) and specialized nurses.
Treatment
Surgery is the common treatment for craniosynostosis. The traditional surgeries involve the exposure of the skull, physical breakage of the fused suture region, and the restoration of the scalp. These surgeries all carry the risks associated with surgery in the brain region. Also, the surgeries produce much bleeding (sometimes a blood transfusion is necessary) and leave a large scar, and transient swelling and bruising can occur.
A new surgical technique called endoscopic strip craniectomy has been pioneered by two pediatric surgeons from the University of Missouri Health Care Center. This surgery is much less invasive, produces only a relatively small scar, and leaves little physical after effects
such as swelling and bruising. In the procedure, an endo-scope is used to remove the closed suture through incisions that are only several inches in length. In the more than 100 surgeries performed as of January 2001, most of the infants were in a condition satisfactory enough to leave the hospital the following day. Endoscopic strip craniectomy can only be done on infants under six months of age. After the surgery, the baby wears a protective helmet for several months, which molds the growing head into the correct shape.
Recovery and rehabilitation
Regardless of the type of surgery performed to correct the defects associated with craniosynostosis, the child will be restricted from vigorous activity or rough play while healing. The protective helmet is required for children after endoscopic strip craniectomy, while permanent plates inserted during other corrective surgeries eliminate the need for the helmet. Children who have had surgery to repair craniosynostosis will continue to need periodic examination by the surgeon until approximately age 18, when the skull has grown to its adult size and shape.
Clinical trials
The National Institute for Neurological Diseases and Stroke directly undertakes and funds a range of studies examining the mechanisms of early neurological development. However, there are no clinical trials scheduled to study craniosynostosis as of January 2004.
Prognosis
The outlook for a complete recovery for a child with craniosynostosis depends on whether just one suture is involved or whether multiple sutures have closed. Also, the presence of other abnormalities can lessen the confidence of a satisfactory outcome. Without surgical intervention, craniosynostosis can lead to increased brain pressure, delayed mental development, mental retardation , seizures , or blindness. After surgery is accomplished, the prognosis is excellent.
Resources
PERIODICALS
Johnson, D. "A Comprehensive Screen of Genes Implicated in Craniosynostosis." Annals of the Royal College of Surgeons of England (November 2003): 371–377.
OTHER
Sheth, R.D. "Craniosynostosis." eMedicine. January 22, 2004 (March 30, 2004). <http://www.emedicine.com/neuro/topic80.htm>.
National Institute of Neurological Disorders and Stroke. Craniosynostosis Information Page. January 22, 2004 (March 30, 2004). <http://www.ninds.nih.gov/health_and_medical/disorders/craniosytosis_doc.htm>.
University of Missouri Health Care. "Craniosynostosis: A New and Better Treatment." MU Health. January 19, 2004 (March 30, 2004). <http://www.muhealth.org/~neuromedicine/craniosynostosis.shtml>.
ORGANIZATIONS
March of Dimes Birth Defects Foundation. 1275 Mamaroneck Avenue, White Plains, NY 10605. (914) 428-7100 or (888) 663-4637; Fax: (914) 428-8203. askus@ marchofdimes.com. <http://www.marchofdimes.com>.
National Organization for Rare Disorders. 55 Kenosia Avenue, Danbury, CT 06813-1968. (203) 744-0100 or (800) 999-6673; Fax: (203) 798-2291. [email protected]. <http://www.rarediseases.org>.
World Craniofacial Foundation. 7777 Forest Lane, Suite C-621, Dallas, TX 75251-5838. (972) 566-6669 or (800) 533-3315; Fax: (972) 566-3850. [email protected]. <http://www.worldcf.org/cran_3c5.html>.
Brian Douglas Hoyle, PhD
craniosynostosis
oxycephaly
—oxycephalic (oksi-si-fal-ik) adj.