In 1906, a French neurologist first described the features of this syndrome that now bears his name. Apert syndrome results from a mutation (or change) in a single gene located on chromosome 10q. There are actually two different mutations on this same chromosome that can produce Apert syndrome, called: Ser252Trp (or S252W) and Pro253Arg (or P253R). Studies have shown that there may be slight differences in how a child is affected depending upon which one of these two mutations a child develops, and that it is not always possible to tell which mutation a child has from just an examination. Currently, no one knows exactly what causes this mutation to occur. Almost in all instances both the mother and father of a child born with Apert syndrome have normal genes, and the mother does “everything right” during her pregnancy. The process of combining a mother and father’s genes together to create a child is quite complicated. In bringing together of both parents’ genes many changes normally occur in different places on these genes. If a mutation occurs in just the right spot, Apert syndrome results. One study showed that for all the families tested the mutation seemed to have started with the father even though the father did not have Apert syndrome himself. The chances of two parents who do not have Apert syndrome of having a child with Apert syndrome has been estimated to be somewhere between 1:60,000 - 120,000. Could you have Apert syndrome and not know it? The answer is: no. If a young adult with Apert syndrome decides to have a family, this condition would be inherited in what is called an “autosomal dominant pattern,” meaning that there would be a 50:50 chance of passing on the Apert trait for each birth. If both parents have Apert syndrome, there would be only a 25% chance of them not passing on this condition for each birth. Today, it is possible for someone with Apert syndrome to ensure that this syndrome does not get passed down to his or her children by using in-vitro fertilization, testing, and then selecting an embryo that does not have the Apert gene for implantation.
Apert syndrome affects multiple places around the body; some children will have certain traits, while others may not. The list below is not complete but does include most of the more common findings. Certain physical findings are more likely to show up depending upon which of the two Apert genes a child has; for example, children with the S252W mutation are more likely to have a cleft palate whereas children with the P253R mutation are more likely to have a “rosebud” hand (where the thumb is fused together with the rest of the fingers). It is likely that there are other genes that we cannot test for today, which are influencing whether or not certain traits are present.
Many parents may note that their child sweats more than other children. This condition is called “hyperhidrosis” and is caused by overly active sweat and oil glands in the skin. When children with Apert syndrome enter adolescence they often develop severe acne, likely the result of these hyperactive glands. Fortunately, there are particular medications (such as Accutane®) that are very helpful in controlling severe acne when it occurs.
The skull is made up of separate bones and the spaces between these bones are called sutures (if you want go to see a picture of these sutures click on the Craniosynostoses section). In Apert syndrome all these skull sutures eventually fuse together, but usually the first sutures to fuse shut are called the coronal sutures. These two sutures run from ear to ear across the top of the head; the right and left coronal sutures meet at the top of the skull at the soft spot, or “anterior fontanel.” With these sutures fused shut, the skull is not able to grow in a normal way to accommodate the growing brain. Specifically, the skull cannot get larger from front to back so instead the brain grows upward making the head taller. In most children with Apert syndrome the soft spot will split open down the middle of the forehead, like a seam tearing open in a tight pair of pants, leaving a large open area of the skull from front to back that feels soft. Eventually, over time this open area will completely close up with bone. However, some children with Apert syndrome may have a different skull shape, with a ridge of bone running vertically up and down the center of the forehead that can cause the skull to grow even taller. We have noticed that children with Apert syndrome seem to have 3 different types of skull growth patterns, which we call: Type I, II or III. The most common is Type I, with a wide-open soft spot and a skull that is not particularly tall. Type II skull shapes are taller and may or may not have a ridge running up and down the center of the forehead. Type III skulls, which are the least common, are very tall and the forehead is quite recessed. We believe that the type of skull shape should determine the timing for skull surgery, and this is further discussed in the Treatment section.
Inside the brain are fluid-filled areas called ventricles, which contain cerebral spinal fluid (or CSF). One could think of these ventricles as little lakes inside the head that are connected to each other by small streams. Occasionally, these ventricles become filled with too much fluid, causing problems. Most all children with Apert syndrome have ventricles that are larger than normal but, unless a neurosurgeon determines that the enlargement is associated with an increase in pressure, no treatment is required for these enlarged ventricles. However, in some children these enlarged ventricles continue to expand and can begin to “squish” the brain from the inside, which is called “hydrocephalous.” In this case, a pediatric neurosurgeon may recommend placing a shunt. This is basically a tube with one end placed inside the ventricle of the brain and the rest of the tube tunneled under the skin down to the abdominal cavity, in order to drain off fluid. In Dallas, we have noted that only about 18% of all children with Apert syndrome have required a shunt. This percentage may be higher than actually needed because many children treated elsewhere before coming to Dallas may have shunts placed by neurosurgeons who might not realize that Apert children normally have enlarged ventricles and that these do not always require a shunt. Another option for treating hydrocephalous, which is still being studied, is an operation called a third ventriculostomy (or ETV). Instead of using a shunt to drain off fluid, a connection is made between two ventricles, like creating a new stream between two lakes. Although this operation has a number of advantages, it probably only works well in selected cases. In general, as long as a child’s head circumference measurements stay more or less on the same point on the growth curve, it is unlikely that any hydrocephalous treatment will be necessary.
Another condition that may occur inside the skull is called “cerebellar tonsillar herniation,” or a “Chiari malformation.” The floor of the skull has a hole called the foramen magnum, through which the spinal cord exits. Sometimes, part of the brain (the cerebellar tonsils) can get pushed down into this hole like a cork in a wine bottle. When this happens this Chiari can reduce the flow of cerebral spinal fluid around the brain stem and might cause a particular type of sleep apnea called central apnea. With central apnea, a child every now and then “forgets” to breathe while asleep, lowering oxygen levels to the brain. There is no way to tell if this is happening by watching your child sleep, it is necessary to test for this by doing an overnight sleep study. A Chiari can also lead to a condition in the spinal cord called a syrinx (or syringomyelia) where the center of the spinal cord gets enlarged with fluid, causing a small bulge in the cord. Although Chiari malformations were once believed to be very rare in Apert syndrome, we have found that it is actually much more common than originally thought, occurring in almost 30% of all our patients in Dallas (Publication #46). We believe that it is important to check for a Chiari early in life and to continue to monitor for the development of one because we have also noted that they usually are not present at birth but can develop over time. In addition, we have learned that the development of this condition may reflect an increase in intracranial pressure signaling the need to enlarge the skull to create more room (Publication #18). Unfortunately, there are no signs that might be obvious to a parent if their child has a Chiari. So, what is the best way to evaluate your child’s brain to look for some of these conditions? At the current time most craniofacial surgeons routinely order CT scans on children with Apert syndrome. However, in Dallas, we have pretty much stopped getting CT scans altogether for a number of reasons. To begin with, it is very hard to tell if a child might have a Chiari from looking at a routine CT scan; MRI scans are much better for evaluating the brain, especially in the region of the brainstem. We have also learned that by doing a careful physical examination it is possible to tell which sutures of the skull are fused without any x-rays (Publication #26). Finally, there have been a number of good studies that suggest that the radiation associated with CT scans might slightly increase the risk for brain and blood cancers over a child’s lifetime (http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60815-0/fulltext) and there is no radiation with an MRI. In addition to looking at the ventricles and seeing if a child has a Chiari, we also look for other potential changes in different parts of the brain. Children with Apert syndrome may have a poorly formed region called the septum pellucidum, or another area that may not form normally called the corpus callosum. Interestingly, a review of our Apert patients suggests that the absence of these structures does not seem to correlate with a child’s mental development (Publication #46).
One final concern for children born with Apert syndrome is the possibility for raised intracranial pressure. We know that children with Apert syndrome have larger brains. As the brain grows, the abnormal closure of the skull sutures (craniosynostosis) limits the ability for the skull to enlarge in certain directions, which can lead to slightly higher pressures inside the skull, which in turn can reduce blood flow to the brain. Raised intracranial pressure is most often treated by surgically enlarging the skull (see Treatment below), and this operation usually has to be done somewhere between 2 and 4 times during a child’s lifetime. We are not sure exactly what the ideal age is for a child’s first skull enlargement operation. Our research has shown that most other centers first perform this skull enlargement on average around 6-months of age. We believe that doing surgery at this early age is not only unnecessary in almost all cases, but that it will also impair the future growth of the skull, possibly increasing the total number of operations that a child will require over a lifetime. In Dallas, we believe it is safe to delay the first skull surgery beyond 6-months of age to somewhere between 9 and 15-months of age, depending upon the skull type a child was born with. Not only are we convinced that this delay is safe, we believe that by waiting until a child is a little bit older, this can reduce the total number of operations the child must endure. Sometimes parents are told that their child has raised pressure and must have surgery right away. It is very important for parents to find out what makes their doctor convinced of this. Surgeons without a lot of experience treating this condition may wish to operate sooner than is necessary. We have not seen any problems with raised pressure, among children treated in Dallas, before 9-months of age. However, it is important that growing children be closely monitored by experienced physicians to make sure that the intracranial pressure is not getting too high. This monitoring is done a number of ways: having a pediatric neuro-ophthalmologist evaluate the optic nerves (raised pressure can cause bulging of the nerve in the back of the eye), following head circumference measurements with growth, monitoring changes in the MRI scans, performing visual evoked potentials (a measurement of the speed that light travels from the eye nerve to the brain), monitoring overall intellectual development, and looking for signs in older children such as headaches or vomiting. Lastly, it is even possible to put a tiny catheter under the skull to directly measure pressure.
In terms of mental development, most children with Apert syndrome have some degree of a developmental delay. I believe that the multiple hospitalizations and surgical procedures these children endure, may contribute to these developmental delays although certainly there are other factors at work (sleep apnea, central wiring problems, raised intracranial pressure, etc.). An earlier review of around 80 children with Apert syndrome at our center revealed that the average I.Q. score was 78; however today, children with Apert syndrome may have higher scores. A follow-up study done in Dallas suggested that development was not influenced by how old children were when they had their first skull surgery (Publication #46), and that children treated at our center from birth seemed to have higher developmental levels than those treated at other centers (although, there may have been other factors could have influenced this seeming advantage). Some children with Apert syndrome can have I.Q. levels in the low normal range and go on to college. Obviously, an I.Q. test can only test for one form of intelligence. There are so many kinds of intelligence that we cannot test for, such as: musical, creative, social, and artistic, just to name a few. We recommend that parents challenge their children to develop to their fullest potential.
The Eyes and Mid Face
Children with Apert syndrome seem to have big eyes; however, the eyeballs are actually of normal size. The problem is that the bones surrounding the eyes (the “orbits”) cannot grow forward in a normal way. In addition, the eyelid openings usually slant downwards. Some children’s eyes can bulge so far forward (this condition is called “proptosis,” or “exophthalmos”) that the cornea, or lining of the eye, can become dried out developing scars that partially block vision. Occasionally, when children with severe proptosis cry, their eyelids can get temporarily caught behind the eyeball. This condition obviously requires immediate treatment either with a tarsorrhaphy (sewing the outside part of the upper and lower eyelids together) in infants, or by surgically moving the bones of the orbits and midface forward (this is best done at an older age). Some children with Apert syndrome may also develop optic nerve atrophy (weakening, or wasting), which can diminish a child’s ability to see. It is not clear what causes this optic nerve atrophy, but it may be related to chronically high intracranial pressure.
The most commonly seen eye problem, noted in all children with Apert syndrome, is an imbalance of the muscles that move the eyes, called “strabismus”. Often, one of the six muscles (the “superior oblique”) that normally move the eye may be completely absent. Many children with Apert syndrome require eye muscle balancing surgery to prevent a type of visual loss called “amblyopia.”
The midface describes the part of the face between the eyes and the upper teeth. With Apert syndrome this region is smaller than usual and does not grow in a normal way. The deepest part of the face in Apert syndrome is the top of a shorten nose. Because the midface cannot grow forward in a normal way, most children require surgery to move the midface forward more than once over their lifetime. Based on measurements taken from our center’s anthropologist in Dallas, it appears that the face in children with Apert syndrome grows forward only about 1/3 normal speed, and another study suggested that all forward growth stops about age 9 (Publications #24). This smaller midface causes a child’s eyes to look bigger and also contributes to breathing problems caused by the tiny nasal passages.
The ears are usually normally shaped, but may be positioned slightly lower than average. As a result of the midfacial hypoplasia (poor growth), the Eustachian tube of the inner ear does not drain well and children frequently develop fluid behind their eardrums (“serous otitis media”) or can develop multiple ear infections. Most infants require placement of small tubes in the ear to prevent frequent infections and chronic internal scarring. In addition to this ear drainage problem, which does get better as children grow, the bones of the inner ear may be partially fused together contributing to a “conductive” hearing loss. Many adults with Apert syndrome may have some degree of hearing loss, so careful attention to the ears is important in infancy and childhood.
The Mouth, Palate, and Airway
Another issues associated with the midface being too small is that the palate, or roof of the mouth, has a very high arch. This high arch pushes up the floor of the nose making it very difficult for children to breathe through their noses. Another problem with the raised floor of the nose is that parents will notice that their toddler’s noses seem to “run” all the time. This problem will improve with time, but is ultimately fixed in teenage years when the midface is lengthened while normalizing how the teeth fit together.
The palate, or roof of the mouth, in Apert syndrome may have a cleft. Typically, this cleft only affects the back of the palate (secondary palate), and rarely extends all the way to the front. We have noted that about 25% of children with Apert syndrome have an obvious cleft and another 25% have what is called a submucous cleft. A submucous cleft is suspected when the uvula is split. With this condition there is no obvious cleft of the palate, but underneath the mucosa of the palate, the deep muscles are not in the correct location. The remaining 50% of children have no type of cleft. Recently, we have significantly changed the timing for treating clefts in children with Apert syndrome (see Treatment) delaying this repair for many years.
The airway in children with Apert syndrome is almost always compromised. Parents will notice that their children are “noisy breathers;” especially at night, which may be the result of a number of things. The most common cause of this is the poor growth of the midface, which causes the nasal passages to be squished smaller. When babies cannot move air through their noses, they will struggle to breathe at night and their brains will get less oxygen. The roof of the mouth is lower in the back of the throat, almost touching the tongue, making the oral airway smaller. Sometimes the tongue will be slightly floppier in babies, which allows it to fall back and occlude the airway. For this reason it is important for babies to be positioned to sleep on their sides, or stomach. Finally, the windpipe (trachea) maybe slightly narrowed; further contributing to a breathing difficulty. The trachea is normally kept open by C-shaped rings of cartilage (somewhat similar to the wire surrounding the duct that exits the back of a clothes dryer) and these rings can expand when we cough or breath deeply. In Apert syndrome, these rings can be O-shaped, which does not allow the trachea to expand. In addition, children may have something called “reactive airways,” which is similar to having asthma. When this is the case, children may benefit from seeing a pediatric pulmonologist (lung specialist) who may suggest certain types of asthma-type medications. We believe that the very first test that needs to be done on a child born with Apert syndrome is an overnight sleep study in order to measure the child’s ability to breathe normally and get enough oxygen at night.
Fortunately, Apert syndrome is usually not associated with any major heart problems. However, affected children do have a much higher incidence of small holes in their hearts called ASD’s (atrial septal defects) and VSD’s (ventricular septal defects). Rarely a child may have problems with a high heart rate. It is important that all children be screened for these problems by a pediatric cardiologist.
The Stomach and Intestines
Most children with Apert syndrome have reflux (gastro-esophageal reflux, or GER). We believe that this is because of the increased work of breathing that raises pressure in the stomach. This causes the contents of the stomach (including the stomach acids) to travel back up the esophagus and sometimes go into the lungs. When severe, it can cause a baby to turn suddenly stop breathing and turn blue. There are a number of tests that can be done to look for this condition, such as a pH probe during an overnight sleep study, a barium swallow test, or even an upper endoscopy. We recommend that all babies be started on reflux medication to help treat this problem, and stay on this medication for the first 2 years of life. Finally, a few of our patients with Apert syndrome have been found to have a condition called malrotation of the intestines. This condition is best diagnosed by a test called a barium swallow and when found, needs to be treated by a pediatric surgeon.
The Hands and Feet
Perhaps the single most identifying feature of Apert syndrome are the associated syndactylies, or fusions, of all the fingers and toes. During normal development, when a baby is being formed inside of a mother all the fingers and toes start off by being completely fused together. Then a signal is sent to the hands and feet, which results in all the fingers and toes separating. This normal separation process does not occur in Apert syndrome causing most of the fingers and toes to be fused together. Apert syndactylies are classified according to how many fingers are fused together. In the mildest cases, or a Type I hand, only the index, long and ring fingers are fused. If the thumb is fused to the index finger by a thin bridge of skin, this is called a Type II hand. In the more severe cases, all the fingers are fused together (often referred to as a “rosebud hand”) and the thumb has a more complicated fusion to the index finger. Rarely, the thumb may appear to be completely buried underneath the skin of the palm. When the fingernails appear fused together as a single plate, this usually indicates that the bones of the fingers are fused underneath. In addition to these fusions, the index, long, ring and small fingers are all missing the middle joint (called the PIP, or proximal interphalangeal joint). As the fingers grow, they can develop curvatures that can cause the fingers to cross over each other a little. The thumb usually grows in a curved way, away from the other fingers of the hand.
The toes most often have completely separate nails and bony fusions between the toes are rare. When bony fusions do occur, it is usually only between a couple of the toes. The big toes are often shorter than normal, and frequently grow like the thumbs, curving away from the rest of the foot. Although the Apert foot appears very wide, in fact our measurements have shown that they are normal in width, but instead it is the length that is too short. This mismatch in growth makes it difficult to fit shoes properly, and families usually end up buying shoes a size that is too long in order to find a shoe that is wide enough. Over time three “bumps” may grow on the Apert foot: the first is along the inside edge of the foot, next to the big toe. The second is along the outside of the foot, just behind the small toe. The third is on the bottom of the foot, in line with the second toe. The treatment of these bumps, and the syndactylies is discussed in the Treatment section.
Below are examples of the three types of syndactylies, based on the degree of attachment of the thumb. It is possible to get five-fingered hands in almost every child with just two operations.
Type I Type II Type III
Parents may also notice that as children get older, they may not be able to completely raise their arms over their heads (due to restrictions in the shoulder joint), or completely straighten their elbows. The ankle joint is usually located more on the inside of the foot, than in the middle. Finally, fusions of the cervical vertebrae, or bones of the neck, are common with Apert syndrome. For the most part, there are currently no helpful procedures for these joints, although we are looking into an operation that may help the ankle joint over the long-term.
The treatment of a child born with Apert syndrome is complex and is best provided by comprehensive craniofacial teams at major centers. The following is a brief overview of treatment possibilities, with a focus on what we recommend for our patients coming to Dallas for treatment. As the result of our seeing a high number of children with this condition our treatment approach has been radically changed. Today our treatment focus has shifted to first, and foremost, maximizing intellectual development. Our second goal it to siginificantly reduce the high number of operations that children typically undergo. The recommendations that your child may receive could be very different from what we recommend as doctors can vary considerably with what they believe is the best way to treat the various issues associated with this condition.
The first operation most children with Apert syndrome undergo is an operation on their skull, which is performed to relieve pressure on the brain. This operation is done in many different ways. Some surgeons will recommend simply remove a strip of bone – a strip craniectomy - very early in life. Others recommend placing what are called distraction plates (metallic plates that are slowly rotated to lengthen them and enlarge the skull) or metal springs used to expand the skull. The use of metal plates or springs does require two operations, instead of one, with the first operation used to place the distraction devices or springs and the second scheduled months later to take them out. Most surgeons today still recommend a single operation to expand the skull, sometimes interchangeably called a CVR (cranial vault expansion) or FOA (frontal orbital advancement). In Dallas we have abandoned the two-stage operation using distraction plates and will not use spring expansion; in part, based on a study we have published. In this study we compared children with Apert syndrome undergoing distraction of the skull to those treated with a traditional single stage CVR and found that it was not only better to do a traditional CVR (Publication #52), but that is was also easier on the child.
It has been our observation that most other centers tend to recommend a first skull operation sometime around 6-months of age. However, we believe that when these operations are done too early in life, it may cause issues later on. Instead, we recommend determining the best timing for an operation based on the type of skull a child is born with, for example: if a child is born with a Type I skull (a large soft spot) we will recommend delaying surgery until as late as 15-months of age because delaying surgery may eliminate a future skull expansion operation. Most parents worry: is it safe to wait? We examined a large series of children with Apert syndrome and compared those undergoing their first skull operation before a year of age to those having their first operation after a year of age and found there were no differences in overall development (Publications #46). In addition, as an infant gets bigger the operation may become safer because the body is larger and has a greater blood volume. The most common cause for children not surviving skull surgery is from excess blood loss. There have also been some recent studies that suggest, but do not prove, that anesthesia in young babies may not be good for the developing brain. Currently, it is only for the Type III skulls, which are extremely tall, that we will recommend surgery as early as nine months of age.
How is surgery done in Dallas? At our center, we routinely give children erythropoietin before surgery to raise the child’s blood levels before surgery, not only because this can help to prevent the need for blood transfusions (Publications #19), but also because we believe that it may make the operation safer. We also use what is called a “cell-saver” to recycle some of the blood that is lost at surgery, so that it can be given back to the child. Using this combination of techniques, most children do not require any outside blood transfusions. Although the standard of care is to reduce a child’s blood pressure during surgery with the hopes of reducing blood loss, we have noted when blood pressures were lowered the measured amounts of oxygen going to the brain were also reduced. Therefore, after completing a study that showed that lowering the blood pressure during surgery actually did not impact the need for a blood transfusion, we are now doing all our skull operations under normal blood pressures with the goal of protecting the child’s brain (Publications #50). Operations on the skull are always performed as a team, with a pediatric neurosurgeon and craniofacial surgeon working together (which improves the speed and safety of the procedure) along with a specialized pediatric anesthesiologist. Typically, skull surgery takes about two hours but children are under anesthesia for about 4 to 4.5 hours. We do not shave any hair for surgery in Dallas and skull is reached through an incision that extends from ear to ear across the top of the head. Many years ago, I changed the typical straight-line incision to a wavy, “zigzag” incision because I noted that when children get their hair wet, it parts on a straight-line scar (Publications #10). Making the incision in a wavy pattern helps to better hide the scar. The purpose of the surgery is to remove the areas of skull that were affected by the fused suture and reposition the skull to improve blood flow to the brain, while also providing some additional space for growth. One common misconception is that surgery releases a growth constriction. This is not true, and in fact if anything it is the opposite that occurs. When a surgeon removes a strip of bone from the skull, or performs a CVR too early in life, there may be a slight expansion, but then all future growth may be diminished causing a greater degree of increased pressure later. Ultimately, the success of any skull operation will depend upon how well the surgeon was able to create more room inside the skull and if it was done at the right time. In Dallas we never recommend that children be treated with constricting headbands because we are convinced that this has a negative effect on blood flow to the brain (and may possibly impair development). These bands and helmets work by preventing growth in certain directions in order to force the brain to push the skull out in other directions. We have also previously reported our findings concerning the use of metal plates and screws to hold the skull bones together at the end of the operation. We found that when we re-operated on children that had skulls put together by other surgeons using metal plates and screws, with subsequent growth of the skull these plates will end up on the inside of the skull with the screws poking into the brain (Publications #12). This same problem also happens with dissolving plates and screws that are in wide use today. Sometimes, depending on the type of plates, and the age of the child, these dissolving plates can end up in the middle of the skull bone causing an area of relative weakness. Therefore, in Dallas we use only dissolving stitches to put the bones together (Publications #20). At the end of the operation, the scalp is closed with dissolving stitches (never metal staples, as these can hurt when they are removed), the hair is shampooed and then combed. No bandages are necessary, nor are any drainage tubes placed (these are completely unnecessary, and also hurt when pulled out).
After surgery, children usually will spend one night in the pediatric intensive care unit and then are transferred to the floor the following day. Children are usually sent home two days after the operation. The risks of the surgery are very small at experienced centers (Publications #36). The most common complication may be that a child does not get a very good result following skull surgery, so it needs to be done again. Aside from a suboptimal result that needs redoing sooner than it should need to be done, the next most common complication is probably an infection. We have published a 2-Center review of all children undergoing skull surgery (Publications #15) that showed that there were no infections noted in infants undergoing operations for the first time (although this still could happen), but the risk for children undergoing repeat operations was about 5% (we believe this incidence has come down since this was published). What about soreness after surgery? When these operations are performed on older children they tell us that they feel very little discomfort afterwards. Nevertheless, we play soft music in the child’s room after surgery, which has been shown to decrease the amount of pain medicine that a child requires after an operation, and are now using a number of non-narcotic medications that have greatly eased the overall experience for children.
The average child with Apert syndrome usually needs two to four operations on their skull over a lifetime. It is very important that children be followed closely to monitor for raised intracranial pressure until at least early teenage years. In addition, it is also important to monitor for the development of a Chiari malformation, which can progress over time.
Breathing and Sleep Apnea
I believe that the single most important factor influencing mental development in Apert syndrome is not raised intracranial pressure but instead is the amount of oxygen that the brain is receiving while the child is asleep. The inability to breathe normally while sleeping is called sleep apnea. There are two types of sleep apnea: central and obstructive. Central apnea is when the brain “forgets” to breathe. This is often caused by cerebellar tonsillar herniation (aka “Chiari”), or less frequently from raised intracranial pressure. Obstructive apnea, which is the most common cause of apnea in Apert syndrome, results from a narrowed or blocked airway (most often, compressed nasal passages). If a child is found to have significant sleep apnea, there are different treatments that may be prescribed, beginning with medications. There are a number of medicines that can open up a partially blocked airway in order to make breathing easier. If medications are not completely successful, the next step might be to consider a tonsillectomy. If a tonsillectomy is not successful, the last option short of major surgery is to try CPAP, which is a facemask that is worn at night that will deliver a rush of air each time the child breathes in. CPAP is usually very effective when worn all night; however, most parents find that their child will pull them off at some point during night, making this treatment only partially successful. If none of the above treatments are able to bring a child enough oxygen at night, then surgery is recommended. Depending on a child’s age, either a tracheostomy or a midfacial advancement might be recommended. In Dallas, for a number of reasons we recommend tracheostomies for children under the age of 6 years, after which we will consider advancing the midface.
Surgery of the Midface
There are three basic operations used to bring the midface forward in Apert syndrome: the LeFort I, the LeFort III and the monobloc. The LeFort I brings the lower midface forward from the level of the upper teeth to the nostrils, but this is usually not done until children have completed their growth. The LeFort III brings the entire midface forward in one piece from the upper teeth to just above the cheekbones and the monobloc brings both the midface and the forehead forward together at the same operation. Some surgeons believe the monobloc is a very good operation for Apert syndrome. In my opinion the only advantage to this procedure is that it brings the forehead and midface forward at the same time, potentially saving a child an operation. However, there are many reasons that this operation is not offered to our patients in Dallas. To begin with the ideal time to bring the forehead forward is not the same as the ideal time to bring the midface forward. More importantly, studies have shown that the monobloc operation has a high risk for very serious infections (Publications #8, 24, 36). This may be why the LeFort III is currently the most commonly performed operation for treating the midface in Apert syndrome. Although the LeFort III is a major operation, of all the different procedures done for Apert syndrome it has the greatest impact on normalizing a child’s appearance and improving breathing at night. Once again, in my opinion, most surgeons perform this operation too early; our data suggests that other surgeons operate on average at age 5. We have recently completed a study that showed that following this operation midfacial growth ceases, so when performed at an early age it will most likely need to be repeated when the child gets older. Based on the results of our study we have found that if surgery can be delayed until after age 7 (and appropriately over-corrected), it is very unlikely that a child will ever need to undergo this operation a second time. The LeFort III is performed through the same incision, on the top of the child’s head that is used for operating on the skull. The bones of the midface are cut across the top of the nose, along the floor of the orbit (under the eye), and down the sides of the cheekbones. No scars are put on the child’s face. After the bones are cut, the midface is moved forward and with the traditional LeFort III, these bones are held in position with bone grafts (taken from the skull) and plates and screws. In young children, the teeth used to be wired together for 4-6 weeks. In older children who have completed facial growth, a LeFort I may be done at the same time as a LeFort III.
In 1998 I developed what is called a halo-distraction technique for the LeFort III. This is a technique utilizes a device called the RED (Publications #17, 24), which is actually not red, but purple in color. It gets its name for being a Rigid External Distraction device. The RED is used primarily in children because it is usually not necessary for teenagers who have finished their growth, unless the midface is too recessed to be treatable with a traditional LeFort III. With the RED procedure the bones of the mid face are cut loose then instead of pulling the midface forward and filling in the gaps with skull bone, the skin is closed and a halo is attached to the outside of the skull with 8-10 screws. A splint (U-shaped piece of plastic) is attached to the upper teeth and two wires extend forward from this splint to attach to the halo. The forward pull of the midface comes from the dental splint. Many surgeons choose to attach the halo to the bones of the face using wires that poke through the skin of the face. I believe that it is better to not use any wires going through the facial skin because they leave permanent scars that I would not want my own child’s face. The parents, or the child, turn two screws on the device 2 to 3-times day in order to slowly (and painlessly!) bring the midface forward. The children are allowed to eat soft foods, may go to school, and can even go swimming while wearing the RED. For some children wearing this device after surgery is easier than for others. Seven to eight weeks later (some doctors make children wear this for much longer), the device is removed with a 20-30 minute anesthetic. One advantage of using the RED device is that it is a smaller operation than a traditional LeFort III, but the greatest advantage of the RED device is that it enables surgeons to move the midface much further forward than is possible the traditional technique (based on a study done at our center). We have treated over 125 children with this technique, and continue to make fine improvements in this procedure.
Two different children, picture above, with Apert syndrome undergoing a halo-distraction LeFort III. Other pictures are available in our published studies.
Treating the Hands and Feet
Usually, the first thing a new parent notices about their child with Apert syndrome is that they are unable to count individual fingers and toes because they are all fused together. The operation to separate these fusions is more complicated in Apert syndrome than it is when digits are fused in children without this syndrome. In Dallas we separate all 10 fingers and toes in just two operations. I believe that no fingers should ever be “thrown out,” but unfortunately this is still done by many surgeons today. Based on my experience, it is almost always possible to get 10 fingers, and I have learned that having a five-fingered hand becomes increasingly more important to children as they grow older (Publications # 21). If a surgeon tells you that it is not possible to get a five-fingered hand, I would recommend getting another opinion. It has also been our observation that most doctors are either unable, or are unwilling, to separate the toes. It is true that separating the toes does not improve a child’s ability to walk or run, and it could be argued that the only functional benefit to separating the toes is that it allows some child to wear “flip flops.” However, we have heard from many parents whose children did not undergo toe separations that when they are older they do not want to do things like go to a swimming pool, go to the beach, or take their shoes off to run in the grass, because of the embarrassment they feel about how their toes look, all fused together. In fact, separating the toes does offer a very significant “functional” improvement because it helps the child to live a more normal life. It is a common misconception that separating the toes widens the foot. In fact, the skin bridges between the toes in no way helps to keep the toes closer together. The width of the toes is determined by the way the bones of the toes grow, some grow straight and some grow curved. In addition, the toes do not grow forward in a normal way, although the width of the foot remains normal. This limited forward growth changes the length to width ratio of the foot, which makes the foot seem excessive wide.
In Dallas, separating the fingers and toes is done by a highly experienced team, which enables us to accomplish a release of all 10 fingers and toes in just two operations. Most other centers recommend three or more operations just to separate the hands; not only does this force the child to undergo more operations than necessary, it doesn’t take into account the potential negative effects of multiple anesthetics on the growing brain. Therefore, we limit the releases to just two operations. Usually, children just spend one night in the hospital, and then go home the next day. We send the children home in casts that can be unwound at home 3 - 4 weeks later. While it is not necessary to do dressing changes after this surgery, in some instances it can improve the final results. Three months after the first stage release, the second stage is done to complete the separation of all the fingers and toes. For most children the skull surgery comes 3 months after the 2nd stage release of the syndactylies. However, this sequence may be different depending on the type of skull growth.
Once children are older than 10-years of age, another different operation can be done to improve both function and appearance. At this time, bends are put in the middle of all the fingers, and the thumbs are straightened. This operation improves fine motor skills and also makes the hand look more normal. This later procedure is especially useful for helping a child button shirts, pull up zippers and tie shoes. At the same time, any sore “bumps” on the foot can be reduced and any bent toes can be straightened.
Examples (below) of released hands (top and middle row, Type I hands; bottom row, a released Type III hand with bends put in the left hand already).
Examples (below) of a patient with un-released toes, and one in whom the toes that have been separated:
Another reasons to release the toes (below).
The Big Picture
Most children with Apert syndrome undergo far too many operations, more than they need to, and too much time is spent in the hospital. Furthermore, in light of recent studies raising questions about the effects of multiple anesthetics on development in growing children, it is all the more important to limit the number of operations done to a child with Apert syndrome. Too often, children with Apert syndrome are put to sleep for a single small operation done by one specialist who does not coordinate the care with other specialists, so multiple operations are done every year. It is important that every time a child with Apert syndrome needs to go to sleep in the operating room, all the specialists coordinate their care so that as much gets done as possible with each anesthetic. For other patients, important tests may not be performed at the right time and as a result, irreversible problems can develop. Ideally, families need a single “quarterback” to oversee and coordinate the care among all the different subspecialists that are needed to treat Apert syndrome. As our experience in treating this condition has grown, we have come to realize that the primary goal in caring for a child with Apert syndrome must be the prevention of avoidable developmental delays, in order to provide a child the best chances for living a normal life. It is also critical that the correct operation be done the first time, and that all efforts are made to reduce complications. Operating too soon can seem like a good idea, but most often causes further problems with growth that require even more operations to correct. It is not uncommon to see children who have begun treatment at other centers but do not seem to have made any progress, in essence they have undergone the discomfort of surgery and time in the hospital, but the same operation needs to be redone again because it was done too early or not well enough. I believe that it is very important that children be given substantial blocks of time away from the hospital so that they can grow and develop to be their best. Parents need to bring their child to the most experienced craniofacial centers they are able to travel to. Treatment recommendations are constantly changing over time, and will also vary from center to center. It is important to take the time to discuss an overall treatment plan with your doctor, and make sure that all your questions get fully answered (see Choosing a Doctor). Take the time to learn as much as you can, get more than one opinion, and search until you find that physician that you feel comfortable with coordinating all the care your child will need.
Jeffrey A. Fearon, MD, FACS, FAAP
Director, The Craniofacial Center, Dallas Texas