Physician: Education: Descriptions of Disorders

Craniosynostosis occurs approximately 1 in 3000 births. This calculation includes patients with both isolated (not associated with a genetic syndrome) and syndromic (in which craniosynostosis occurs along with other specific physical features) forms. The majority of cases are isolated, with syndromic forms being much less frequent (incidence in the range of 1 in 25,000 to 1 in 100,000 births).

The most obvious manifestations of craniosynostosis is an alteration of head shape. The actual shape, however, will differ depending on which skull bones have closed. If this is known, the head shape can be predicted based on what we know about normal growth patterns. In infants and children, the skull is made up of several distinct bones. Areas where two bones line up next to each other are called sutures. It is important that these bones have some independent movement to allow for compression of the skull as it passes through the birth canal, and also to allow for head growth as the developing brain expands. Skull growth occurs as more and more bone is laid down at the suture line, essentially moving one bone further away from the bone on the other side of the suture. This produces growth in a direction perpendicular to the direction of the suture line. When the suture has fused, however, this growth is no longer possible. As the brain continues to grow, the skull can expand in a direction parallel to the closed suture (assuming the other sutures are open). Closure of the sagittal suture will prevent the skull from increasing in width. Continued brain growth will force the skull to grow in a lengthwise direction producing a long, narrow head shape called dolichocephaly. Closure of the coronal sutures will prevent the skull from increasing in length from front to back. When the coronal sutures have fused, the only option is for the skull to increase in width. This produces a shortened, broad head shape called brachycephaly. Closure of the lamboid sutures is fairly uncommon. When one lamboid suture is truly fused, however, it causes the back of the skull to become flattened on that side. Because growth is encouraged perpendicular to these sutures (which lie at the back of the skull), the opposite side of the forehead may become somewhat prominent. When both of the lamboid sutures have closed, the skull appears short and broad (brachycephalic). Closure of the metopic suture (which runs down the middle of the forehead) may lead to a ridge which has been likened to the keel of a boat. It forms a triangular shape to the forehead (when viewing the patient by looking down at the top of his head). This condition is called trigonocephaly. More complex head shapes are formed when only one of a pair of sutures (i.e., one coronal or one lamboid suture) is fused. In this case, growth is only restricted on one side of the head and leads to an uneven or asymmetric head shape, a condition called plagiocephaly. Other head shapes can result if multiple sutures are involved. The most severe head deformity, a cloverleaf or trilobular skull is caused by very early closure of the metopic, coronal, and lamboid sutures. In this case, the only direction available for brain growth is upward, to and often through an open sagittal suture. Aside from cosmetic concerns, craniosynostosis can have some very serious medical sequelae. The prime concern is for an increase in the pressure inside the skull if not enough room is available for the brain's continued growth. This increase in intracranial pressure can be devastating, initially causing headaches and vomiting, and leading to blindness, hearing loss, respiratory depression, and death. The discovery of increased intracranial pressure is an urgent indication for surgery to open the fused suture(s) and relieve the pressure of the brain. Genetics

Craniosynostosis may occur for many reasons. Some cases are inherited, and some are due to external (non-genetic) factors. The majority of inherited forms are dominant, meaning that an affected individual has a 50% chance of passing the condition on to his or her children. Not all patients with a dominant form of craniosynostosis have inherited this from a parent. A patient may be the first one in the family who is affected, due to a new or spontaneous change in his genetic information (mutation). However, once this change has occurred, the patient carries the 50% risk for passing on the disorder to each of his or her offspring. When a child is first recognized to have craniosynostosis, the parents and other family members may be examined at that time. This is because these dominant conditions are typically quite variable. A parent who is very mildly affected may never have been recognized as having an abnormal head shape. Once a more significantly affected child is diagnosed, however, a careful examination may reveal subtle differences in head shape in one of the parents. While this is unlikely to cause any health concern for the parent, it is relevant in that they may have an increased risk for other affected children in the future. Other forms of craniosynostosis are inherited in a recessive manner. This means that each parent of an affected child is a healthy and unaffected carrier for the disorder. This couple has a 25% risk of recurrence for each future pregnancy. The patient, however, is less likely to pass on the disorder, as his/her mate must also "carry" the same hidden condition in order to produce an affected child. Non-genetic factors that can cause craniosynostosis include compression of the fetal head during development. This can be due to crowding in the uterus from multiple gestations (twins or triplets), large uterine fibroids, or an abnormally narrow shape to the uterus. Certain medical conditions in the infant (such as a hyperactive thyroid, thalassemia or sickle cell anemia, among others) are also known to be associated with an increased risk for craniosynostosis.

Although the exact reasons for premature closure of the cranial sutures are unknown, there is a growing interest in what has been termed "sutural biology". Earlier works suggested that it was the continued growth of the brain which pushed against the skull and was the impetus for expansion. When the growth stopped at maturity, there was no longer a need for the sutures to remain open, and the sutures would then close naturally. The physiology of the sutures themselves depended on the surrounding mechanical forces; sutures located in the midline (such as the sagittal suture) would be expected to receive equal forces from either side, and formed what is called an end-to-end suture. However, sutures located on one or the other side of the skull (such as a lamboid or coronal suture) received unequal mechanical forces. In this case, the suture ends would not meet evenly, but rather formed a beveled suture, with one side overriding the other. There was felt to be a functional difference in these two types of sutures, as only the end-to-end sutures would show the excessive bone growth leading to a ridge of bone which is sometimes seen on physical exam in craniosynostosis. Newer investigations have focused on the particular genes involved in craniosynostosis. These include the fibroblast growth factor receptor (FGFR) gene family (implicated in Crouzon, Apert, Jackson-Weiss and Pfeiffer syndromes), TWIST (causative gene for Saethre-Chotzen syndrome) and MSX2 (Boston-type craniosynostosis). For example, the product of the FGFR2 gene is produced at the sutures when they are open and the cells are "undifferentiated" - meaning that they still have an unlimited growth potential. However, when a mutation causes the gene to produce too much of the FGFR2 product, the bone cells then respond by ceasing their proliferation and producing osteopontin. This is a substance produced by mature bone cells and indicates the loss of continued cell division. Thus, no additional expansion would occur at that suture, causing a functional closure. The precise role of other genes in craniosynostosis remain to be seen, and will likely become evident in the near future.

Usually, craniosynostosis is suspected on the basis of an unusual head shape. Plain X-rays may show that a suture(s) has closed, but is not very accurate in making the diagnosis. The preferred imaging is with a 3-dimensional CT (computerized tomography) scan. This test uses X-rays to produce multiple pictures at various levels of the skull. A computer is used to compile the pictures and produce a 3-dimensional image of the skull and sutures. This method is very accurate in assessing whether fusion between bones has occurred.

The treatment of craniosynostosis is surgical. Surgery is generally recommended if the closed sutures have lead to an increase in pressure on the brain or to marked skull deformity. The fused suture(s) can be removed and the shape of the skull remodeled to form a more natural shape. Such surgery is often performed by a neurosurgeon and a craniofacial plastic surgeon working together. In more severe cases, the surgery may be done in stages to achieve the best result.

In cases where the head shape is abnormal but the sutures have not closed, a nonsurgical approach to reshaping the head is available. A cranial molding helmet can be fitted to the child. This method uses the child's own head growth to help reshape the skull, by allowing growth in areas which appear flattened, and restricting growth in areas which appear prominent. The helmet is generally worn almost constantly for a period of weeks to months and is most successful in younger infants. Once the child approaches one year of age, the rate of head growth slows and the helmet therapy is less successful.

Craniofacial Disorders On-Line Discussion Groups

Pediatric Neurosurgery - Craniofacial Anomalies
Craniosynostosis
Ask the Craniofacial Doc
Classification of previously unclassified cases of craniosynostosis
Craniofacial & Maxiofacial Surgery in Children & Young Adults
Craniofacial diseases
Parents of Children with Craniosynostosis
Personal Side of Craniofacial Differences
OMIM 218500
CRS1 gene
OMIM 123100
Craniosynostosis Syndromes (FGFR-Related)

Fernbach SK, McAlister WH.
Craniosynostosis 1998: concepts and controversies. Invited commentary: posterior deformational plagiocephaly.
Pediatr Radiol 28(9):722-8, Sept 1998. abstract

Huang MH, Mouradian WE, Cohen SR, Gruss JS.
The differential diagnosis of abnormal head shape: separating craniosynostosis from positional deformities and normal variants.
Cleft Palate Craniofac J 35(3):204-11, May 1998 . abstract

Jabs EW.
Toward understanding the pathogenesis of craniosynostosis through clinical and molecular correlate.
Clin Genet 53(2):79-86, Feb 1998 . abstract

Kapp-Simon KA.
Mental development and learning disorders in children with single suture craniosynostosis.
Cleft Palate Craniofac J 35(3):197-203 May 1998 . abstract

Liptak GS, Serletti JM.
Pediatric approach to craniosynostosis.
Pediatr Rev 19(10):352-9, Oct 1998. abstract

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