Craniofacial Deformities: Apert Syndrome

So what exactly is Apert Syndrome? Babies born with Apert Syndrome (Also known as Alpert's Syndrome) have abnormal head shapes, webbed feet and toes, bulging eyes, and a sunken appearance in the middle of the face. An abnormal shape of the head occurs because some of the bones of the skull fuse prematurely. This premature fusion causes the skull to stop growing too soon and this affects the shape of the baby's head and face. The baby also suffers other symptoms that are not visibly present and these symptoms include hearing loss and frequent ear infections which result from a cleft palate (an opening in the roof of the mouth). Approximately thirty percent of babies born with Apert Syndrome are born with a cleft palate. Also, because of a smaller nose and air passages, the baby may have some difficulty breathing and the breathing may be somewhat noisy. Other symptoms associated with the disease are crowded teeth (resulting from an underdeveloped upper jaw), vision problems (because of shallow eye sockets), overactive sweat glands, and acne. As was previously mentioned, babies with Apert Syndrome also exhibit webbed feet and hands. The severity of the webbing of the feet and hands can vary. Some infants may have only three digits webbed together while others may have all of them fused. And as if that wasn't enough, individuals born with Apert Syndrome may also experience mild to moderate mental retardation. About fifty percent of children with Apert Syndrome are affected. However, there is a bright side and that is that as the child grows older it may catch up to the other children (The National Craniofacial Association). While none of these symptoms is particularly deadly, they all prevent the baby from living a normal life.

Apert Syndrome, a very rare disease, is an autosomal dominant disease. In other words, only one copy of the altered gene in each cell is needed to cause the disease. According to Genetics Home Reference, "almost all cases of Apert syndrome result from a sporadic new mutation, meaning neither parent has the disorder." According to an article in the Turkish Journal of Medical Sciences (Kilic et al., 2004) men who have children with Apert Syndrome have a higher incidence of mutations. At first it was thought that older men were more likely to have these mutations, but when a rather large number of young men were found to have an even greater mutation rate, people in the medical community realized that many other factors besides age were involved. While Apert Syndrome is not a particularly deadly disease, it has many negative effects on the health of the individual who is plagued with the disease. Also, it has many negative effects on the emotional state of the baby's parents who know very well that there loved one faces a very judgmental society in the future.

It's rather interesting to note that this disease is very rare. According to Genetics Home Reference, this disease affects somewhere around 1 in 100,000 individuals. However, an article from the Turkish Journal of Medical Sciences (Kilic et al., 2004) reports that the disease affects 1 in 50,000 to 80,000 births. Either statistic still puts this disease in the 'rare' category.

The cause of Apert Syndrome is rather complicated. There is a gene called FGFR2 (fibroblast growth factor receptor 2). This protein plays an important role in processes such as cell division, the regulation of cell growth and maturation, and embryonic development. The FGFR2 protein is very important because it participates in the growth of bone (especially during the development of an embryo). Because of this protein, immature cells in the growing embryo are 'ordered' to become full fledged bone cells in the hands, feet, and head. Well, when the FGFR2 gene goes under a mutation, things end up going haywire. There are two types of mutations. In one type the amino acid "serine is replaced by tryptophan at position 252 in the protein's chain of amino acids" (Genetics Home Reference). In the second type of mutation, arginine replaces proline at the 253^rd position. The alteration of the gene causes prolonged signaling. This is not good because it leads to the premature fusion of bones in the hands, feet, and head.

It's not all that difficult to diagnose Apert Syndrome. A skull x-ray which is given shows the premature closure of skull sutures. X-rays are also done on the hands and feet to determine the severity of the bone problems. Hearing tests are also given since hearing problems have been found in individuals with the disease. On occasion the characteristics of Apert Syndrome can be detected during an ultrasound examination. This is most effective if the ultrasound is done when the fetus is about four months old. If the doctor suspects that the fetus has Apert Syndrome then the doctor may offer the mother genetic testing. The mother can undergo a form of prenatal testing called amniocentesis. Essentially, fetal cells are analyzed for the mutations that cause Apert Syndrome. It typically takes about a month to get the results back (Encyclopedia of Genetic Disorders).

The treatment of Apert Syndrome is not all that easy. The individual with the disease may have to undergo a number of surgeries to make the skull and face more normal. This would be done at about three to four months of age. First, the infant would have to have its skull totally reshaped to correct the top of the skull. After that, the space inside the skull and the size of both eye sockets would be increased by having "frontal orbital advancement." Sometime later, perhaps just before starting school, the sunken in appearance of the face would be corrected. After this the jaw would be widened and the upper face would be narrowed by performing facial bi-partition. As the child progressed through its teen years it would have to receive an osteotomy. Essentially, the surgeon would have to cut through the bone of the upper and lower jaw to correct further problems, problems including crowding of teeth. Other surgeries would include rhinoplasty (surgery of the nose), genioplasty (surgery of the chin or cheek), eyelid surgery to give it less of a droopy look, and of course separation of the fingers and toes (The National Craniofacial Association). More than plastic surgery needs to be done in order to make the child's life as normal as possible. The individual should also go to a hearing specialist to determine what needs to be done to treat the hearing problems that are associated with Apert Syndrome. Also, we should not forget that hearing problems and an irregular jaw shape can lead to problems with speech and language. The child may have to see a speech therapist in order to be able to develop language skills. There is also a psychological component to this disease. As was previously mentioned, this disease can have a serious effect on the emotional state of the child and the family. As we know, today's society is very judgmental. It might be beneficial to the child if he/she went to a psychologist so that he/she can have a positive self-image. Let's not forget about the parents as many times they will feel guilty. They will feel it is their fault that their child has the disease. Also, it hurts the parents when they have to see their child go under the knife (Encyclopedia of Genetic Disorders).

There are many services provided to parents who have children with Apert Syndrome. There are dozens of Craniofacial Medical Centers throughout the United States. An entire list of these medical centers can be found at the National Craniofacial Association website.

Sources:

Encyclopedia of Genetic Disorders, http://health.enotes.com/genetic-disorders- encyclopedia/apert-syndrome

Genetics Home Reference,

http://ghr.nlm.nih.gov/gene=fgfr2;jsessionid=DD811D9FBBDFBEB8AF433F0708D19229

Genetics Home Reference http://ghr.nlm.nih.gov/condition=apertsyndrome

Kilic, l., Baykara, Y., Semerc&idot, C., Erg&idot, H., Tufan, L. (2004). Apert Syndrome.

Turkish Journal of Medical Medicines, 34(6), 405-408. Retrieved Tuesday November

7, 2006, from the Academic Search Premier Database.

National Craniofacial Association, http://www.faces-cranio.org/Disord/Apert.htm