Apert syndrome is caused by a mutation in the fibroblast growth factor receptor 2 (FGFR2) gene. This gene is located on chromosome 10. Normally, the FGFR2 gene is needed to produce the FGFR2 protein, which signals immature cells in a developing embryo and fetus to become bone cells. When the FGFR2 gene is mutated, it changes the protein and results in premature fusion of the bones in the skull, hands, and feet.
In almost all cases, this genetic mutation occurs randomly and is not passed down among family members.
If a person has Apert syndrome, he/she may pass the condition to his/her children. In such cases, the disorder is passed down as an autosomal dominant trait. This means a child only has to inherit one copy of the mutated gene in order to develop Apert syndrome. Each parent provides one copy (or variation of a single gene) to each child. Therefore, if one parent has Apert syndrome, there is a 50% chance that each of his/her children will have the disorder.
General: Apert syndrome may be diagnosed based on the patient's physical signs and symptoms. Apert syndrome is indicated if an X-ray of the skull shows that the bones have fused early and the fingers and toes are webbed or fused together. X-rays of the hands and feet may be performed. Genetic testing may also be performed to confirm a diagnosis or to diagnose the condition in a fetus.
DNA test: A DNA test may be performed to confirm a diagnosis. A sample of the patient's blood is taken and analyzed in a laboratory for the presence of a mutation in the fibroblast growth factor receptor 2 (FGFR2) gene. If a mutation is present, a positive diagnosis is made.
If a parent has Apert syndrome, prenatal testing may be performed to determine if the fetus has the disorder. Amniocentesis and chorionic villus sampling (CVS) can diagnose Apert syndrome with 98-99% accuracy. However, there are serious risks associated with these tests. Patients should discuss the potential health benefits and risks associated with these procedures before making any medical decisions.
During amniocentesis, a long, thin needle is inserted through the abdominal wall into the uterus and a small amount of amniotic fluid is removed from the sac surrounding the fetus. The fluid is then analyzed for a mutated FGFR2 gene. This test is performed after 15 weeks of gestation. Some experts estimate that the risk of miscarriage ranges from one out of 200-400 patients; it is highest when the procedure is done early in pregnancy, before the two layers of fetal membranes have sealed. A woman's particular risk depends in large part on the skill and experience of the doctor performing the procedure. Some patients may experience minor complications, such as cramping, leaking fluid, or irritation where the needle was inserted.
During chorionic villus sampling (CVS), a small piece of tissue (called chorionic villi) is removed from the placenta during early pregnancy. Depending on where the placenta is located, CVS may be performed through the cervix or the abdomen. The tissue sample is then analyzed for a mutated FGFR2 gene. This procedure may be performed between the ninth and 14th week of gestation. The risks of infection or fetal damage are slightly higher than the risks of amniocentesis. Miscarriage occurs in about two percent of women who undergo this procedure. There appears to be an even higher risk of miscarriage with the transcervical CVS technique compared to the transabominal technique. Other factors that further increase the risk of CVS include having the procedure performed three or more times and having a fetus that is smaller than normal for their age. The physician's skill and experience also play an important role.
Audiogram: If hearing loss is suspected, a doctor may recommend an audiologist, who is a doctor that specializes in hearing. During an examination, the audiologist will ask questions about the patient's medical history and perform a hearing test, called an audiogram, to determine the severity of hearing loss. During an audiogram, the patient wears headphones and is exposed to various sounds that have different pitches and frequencies. The patient is asked to identify each time a sound is heard. The audiologist may also say various words to evaluate the patient's hearing ability.
signs and symptoms
General: The severity of symptoms varies among Apert syndrome patients.
Craniosynostosis: Normally, the seven bones in the skull do not fuse until a person is around two years old. This allows the head and brain to grow. Until the bones fuse, joints (called cranial sutures) made up of strong, fibrous tissue, hold the bones together and remain flexible so the head can grow. In patients with Apert syndrome, the skull bones fuse too early. This leads to the development of many distinct facial features.
Physical characteristics: People with Apert syndrome often have heads that appear abnormally pointed at the top, a condition called acrocephaly. Because the head is unable to grow normally, the middle of the face may have a sunken appearance, the eyes may be prominent or bulging (called exorbitism), the nose may look beak-like, the eyes may be spaced far apart, the roof of the mouth may be narrower than normal, and a cleft palate may be present. In about 68% of cases, some of the bones in the neck are also fused together. Another common symptom is severe acne on the arms and legs.
Syndactyly: People with Apert syndrome typically have webbed or fused fingers and toes. The number of digits that are partially or completely fused varies among patients. In general, at least three fingers on each hand and three toes on each foot are fused together. The second, third, and fourth fingers are most likely to be fused together. In the most severe cases, all of the fingers and toes may be fused together.
Hearing loss: Some patients may experience varying degrees of hearing loss. This is because children with Apert syndrome may have low-set ears with occasional conductive hearing loss and congenital fixation of the stapedial footplate.
Intellectual disabilities: Some patients may also experience intellectual disabilities that range from mild to severe. However, others are able to develop normal intellectual abilities.
Frequent ear infections: People with Apert syndrome have an increased risk of experiencing frequent ear infections. It is believed that ear infections may be associated with a cleft palate in the roof of the mouth. This is because the muscles of the palate also control the opening and closing of the Eustachian tubes; people who have cleft palates may have a dysfunctional Eustachian tube that does not open and close properly. As a result, fluid may buildup in the middle ear, making it vulnerable to infections.
Sleep apnea: Sleep apnea is common among people with Apert syndrome. Sleep apnea is a serious condition that occurs when a person stops breathing for short periods of time during sleep. Because sleep apnea causes individuals to wake up frequently throughout the night, patients are often drowsy during the day.
Vision problems: People with Apert syndrome typically have shallow eye sockets, which often makes the eyes look like they are bulging. Having shallow eye sockets increases the risk of developing vision problems, such as blurred vision. It also causes the eyes to have a laterally down-sloping slant.