Acrocephalosyndactyly type 1 (ACS1)

Related Terms

Acrocephalosyndactyly, Acrocephalosyndactyly type 1, acrocephaly, ASC 1, autosomal dominant trait, craniosurgery, craniosynostosis, FGFR2 gene, fibroblast growth factor receptor 2, fibroblast growth factor receptor 2 gene, intellectual disabilities, midface hypoplasia, syndactyly, syndactylic oxycephaly.

Background

Apert syndrome, also known as acrocephalosyndactyly type 1 (ACS1), is a rare genetic disorder that occurs when the bones in the skull fuse together sooner than normal. This prevents the head from growing normally and affects the shape of the face. Some of the child's fingers and toes may also be webbed or fused together. In addition, some people may have intellectual disabilities that range from mild to severe.
Researchers estimate that Apert syndrome affects about one out of 65,000-100,000 individuals at birth.
Early diagnosis and treatment is important to ensure that the child is able to meet his/her maximum potential for growth and development. Children with Apert syndrome need to undergo surgical procedures at an early age (usually when they are three months old) in order to relieve pressure on the brain and allow the head to grow. Several surgeries are generally needed to separate the abnormally fused skull bones. The prognosis varies from child to child. Additional surgeries may be performed to improve the patient's facial appearance and to separate fused fingers and toes.

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.

Diagnosis

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.

Complications

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.

Treatment

General: Early diagnosis and treatment is important to ensure that the child is able to meet his/her maximum potential for growth and development. The condition is treated with surgical procedures that separate the abnormally fused skull bones and allow the head to grow. Additional surgeries may be performed to improve the patient's facial appearance and to separate fused fingers and toes.
Physical therapy: Physical therapy may help people with syndactyly (webbing or complete joining of fingers and/or toes) improve the function of their hands and feet. A variety of techniques, including exercises, stretches, traction, electrical stimulation, and massage, are used during physical therapy sessions.
Occupational therapy: Occupational therapy may help people with syndactyly learn how to perform everyday tasks, such as feeding and dressing, despite their disabilities.
Hearing aids: Individuals who experience hearing loss may benefit from hearing aids. These battery-operated devices are available in three basic styles: behind-the-ear aids, in-the-ear aids, and canal hearing aids. Patients should talk to their doctor to determine the type of hearing aid that is best for them. A behind-the-ear device is used for mild to profound hearing loss. The device has a hard plastic case that is worn behind the ear and connected to a plastic ear mold that fits inside of the outer ear. In-the-ear hearing aids fit completely inside the outer ear, and they are used for mild to severe hearing loss. Canal hearing aids are smaller hearing aids that fit inside the patient's hearing canal. They are used for mild to moderately severe hearing loss.
Craniosurgery: Surgery is typically performed during infancy to separate the abnormally fused skull bones and allow the head to grow. It may also help improve the child's facial appearance. A team of healthcare professionals, including a craniofacial surgeon and brain surgeon (called a neurosurgeon), are involved in the procedure. During the surgery, an incision is made in the infant's scalp and the affected part of the skull is reshaped. Plate and screws, which may be made of material that absorbs over time, are sometimes used to hold the bones in place.
The child usually stays in the hospital for at least three days after surgery. Complications are rare. Some children may require a second surgery in the future. Patients with facial deformities may require additional surgeries to reshape their faces.
Ilizarov procedure: A surgical procedure, called the Ilizarov procedure, may be performed to improve the appearance of a sunken face (called midface hypoplasia). During surgery, the bones in the face are opened up and stimulated to re-grow. This procedure is typically done when the child is six to 11 years old.
Surgical separation of fingers and toes: If possible, fingers and toes that are webbed or fused together may be surgically separated. Although this procedure may improve a person's physical appearance, it does not improve the function of the hands or feet.
Other surgeries: Other surgeries may be necessary to correct bulging eyes, downward slant of the eyes, and upper facial deformities.

Integrative therapies

Physical therapy: The goal of physical therapy is to improve mobility, restore function, reduce pain, and prevent further injury. A variety of techniques, including exercises, stretches, traction, electrical stimulation, and massage, are used during physical therapy sessions. Although physical therapy has not been studied as a possible treatment for people with Apert syndrome, it has been suggested that it may help people with syndactyly (webbing or complete joining of fingers and or toes) improve the function of their hands and feet.
Not all physical therapy programs are suited for everyone, and patients should discuss their medical histories with their qualified healthcare professionals before beginning any treatments. Based on the available literature, physical therapy appears generally safe when practiced by a qualified physical therapist. However, physical therapy may aggravate some pre-existing conditions. Persistent pain and fractures of unknown origin have been reported. Physical therapy may increase the duration of pain or cause limitation of motion. Pain and anxiety may occur during the rehabilitation of patients with burns. Both morning stiffness and bone erosion have been reported in the literature, although causality is unclear. Erectile dysfunction has also been reported. All therapies during pregnancy and breastfeeding should be discussed with a licensed obstetrician/gynecologist before initiation.

Prevention

There is currently no known method of prevention against Apert syndrome.
Individuals who have Apert syndrome may meet with genetic counselors to learn more about the risks of having children with the disorder. If one parent has Apert syndrome, there is a 50% chance with each birth that a child will inherit the condition. However, nearly all cases of Apert syndrome occur randomly and are not inherited.
Prenatal screening and diagnostic tests may also be performed to determine if a mother's fetus has Apert syndrome. However, there are serious risks associated with prenatal testing, including miscarriage. Therefore, patients should discuss the potential health risks and benefits before making any health-related decisions.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS). .
American Academy of Pediatrics. .
Freiman A, Tessler O, Barankin B. Apert syndrome. Int J Dermatol. 2006 Nov;45(11):1341-3.
Holten IW, Smith AW, Bourne AJ, et al. The Apert syndrome hand: pathologic anatomy and clinical manifestations. Plast Reconstr Surg. 1997 May;99(6):1681-7.
Kim H, Uppal V, Wallach R. Apert syndrome and fetal hydrocephaly. Hum Genet. 1986 May;73(1):93-5.
National Human Genome Research Institute (NHGRI). .
National Institute of Neurological Disorders and Stroke (NINDS). .
National Institutes of Health (NIH). .
Natural Standard: The Authority on Integrative Medicine. .
Paravatty RP, Ahsan A, Sebastian BT, et al. Apert syndrome: a case report with discussion of craniofacial features. Quintessence Int. 1999 Jun;30(6):423-6.
Phillips SG, Miyamoto RT. Congenital conductive hearing loss in Apert syndrome. Otolaryngol Head Neck Surg. 1986 Nov;95(4):429-33.
Rajenderkumar D, Bamiou D, Sirimanna T. Management of hearing loss in Apert syndrome. J Laryngol Otol. 2005 May;119(5):385-90.

Causes

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.