Apert Syndrome

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Apert syndrome


Premature closure of the skull bones leading to facial distortion with an unusually tall skull and fusion of the fingers and toes, known as syndactyly, are the major features of Apert syndrome (AS). Another name for this disorder is acrocephalysyndactyly.


A French physician E. Apert first reported in 1906 the syndrome that bears his name. He detailed the skull malformation, midface hypoplasia (underdevelopment) and the hand abnormalities. The hand appears mitten-shaped because of the finger fusion. Intelligence varies from normal to severe mental retardation.

Genetic profile

Apert syndrome (AS) is an autosomal dominant disorder, meaning that a person only has to inherit one nonworking copy of the gene to manifest the condition. In most cases, AS is sporadic meaning that the parents are usually unaffected, but a fresh mutation or gene change occurring in the egg or sperm was passed onto the affected child. For these families the chance to have another affected child is very low. An affected parent has a 50% chance of passing on the abnormal gene to their child, who will then also have Apert syndrome.

Two unique mutations in the fibroblast growth factor receptor 2 (FGFR2) gene located on chromosome 10 were discovered in 1995. This gene directs the development of bone formation. When parental studies were performed, genetic researchers determined that the father passed on the gene causing AS and was usually older than 30 years. No explanation has been found for this unusual finding.

After comparing the physical findings with gene mutations causing AS, researchers noted that one mutation resulted in a much more improved facial appearance after corrective surgery. The other mutation produced a more severe form of syndactyly.


Apert syndrome has been estimated to occur in one of every 60,000-160,000 births. All races and both sexes are equally affected.

Signs and symptoms

At birth the craniofacial (pertaining to the skull and face) appearance is striking. Early or premature closure of the skull sutures (layer of fibrous tissue connecting the skull bones) makes the skull grow taller than normal with a short distance from the front to the back of the head. Always it is the coronal suture connecting the frontal and parietal bones that fuses early. The buildup of pressure on the brain is minimal because the fontanelles, or soft spots, and midline of the skull remain open. Due to the small space within the eye sockets, the eyeballs bulge outward and to the side. Also, the eyelids have a downward slant and cannot completely close.

From the middle of the eye sockets to the upper jaw, the face is sunken in or concave when viewed from the profile. This midfacial hypoplasia causes the upper jaw to slope backward pushing the lower teeth in front of the back teeth.

The mouth area has a prominent mandible (lower jaw), down-turned corners, high arched palate, cleft palate

(an opening in the roof of the mouth), crowded upper teeth, poor contact between the upper and lower teeth, delayed tooth eruption.

Syndactyly of the fingers and toes involves not only soft tissues but also the bones, nerves, and tendons. Flexing of the fingers and toes after the first digit is not usually possible. The thumb can be unattached or fused to the other fingers. Also, the other fingers may or may not be fused to each other in varying degrees. Fusion of the toes is less worrisome. Correction only becomes necessary when walking is difficult.

Most children with AS are noisy breathers. The nose and airways leading to the lungs are smaller than usual. These narrow passageways probably make breathing more difficult. At night if breathing is more troublesome, sleep apnea can occur. This stoppage of breathing while sleeping deprives the brain and body of oxygen. Mental impairment can occur as a result of oxygen deprivation.

Excessive sweating is often seen. Researchers do not know why the sweat glands are overactive. As the children reach puberty, they develop excessive acne. A skin specialist or dermatologist can help to control it.

The height and weight of children with AS is usually normal. However, their learning ability can be affected. A small number of children with Apert syndrome will have a normal level of intelligence while the majority will have some degree of mental retardation.


During the newborn period most babies will be diagnosed after a geneticist examines them. This doctor specializes in diagnosing and explaining hereditary conditions. The unusual facial features and hand syndactyly are unique to AS. Testing for the mutations known to cause AS should be arranged. If a mutation is found then the diagnosis can be made. When a mutation is not found, the physical findings alone can support the diagnosis.

Occasionally during an ultrasound examination, a fetus shows characteristics suggesting AS. This examination is best done after 16 weeks of pregnancy. Ultrasound is the use of sound waves to create a real time image of the fetus. Unlike x rays, ultrasound is not dangerous and the fetus can be examined for size, viability, and birth defects.

An experienced physician or ultrasound technician performing the examination may detect the caved in profile and syndactyly. More than one examination may be necessary to confirm the findings. If AS is suspected then genetic testing can be offered during the pregnancy. The pregnant woman can undergo an amniocentesis to obtain fetal cells that can be analyzed for the mutations causing AS. Amniocentesis is the removal of the amniotic fluid surrounding the fetus by inserting a needle through the uterus. Results may take as long as four weeks.

Treatment and management

The best treatment for AS begins at birth with the correct diagnosis. To provide better care, a craniofacial team should be involved. With the team approach all the specialists are in one center to minimize the number of appointments and corrective surgeries. More important, this team consists of specialists who understand the complex problems of AS and the family's concerns. Included on this team are a craniofacial surgeon, neurosurgeon, otolaryngologist (specialist of the ears, nose, and throat), ophthalmologist (eye specialist), orthodontist, speech therapist, and psychologist. A pediatric nurse, geneticist or genetic counselor, and social worker may also be part of the team during the first few years of the child's life. Many major medical centers will have a craniofacial team or the family can be referred to one.

Working together the craniofacial surgeon and neurosurgeon perform the multiple surgeries to reshape the tower skull. They reopen the prematurely closed sutures between the skull bones and then pull the front of the skull forward to create space within it and enlarge the eye orbits. Average age for these operations is about 4-8 months.

From ages five to nine the child will undergo a surgical procedure called a midface advancement. This technique will correct the concave profile that becomes

pronounced because the upper and lower face grow normally while the middle of the face grows slowly. Corrective facial surgeries continue until the early adult years when growth is finally completed.

The neurosurgeon may perform the operations to unfuse and straighten the fingers. However, a completely normal hand cannot be created.

Frequent ear infections can decrease a child's hearing level. The otolaryngologist can monitor the hearing. Sometimes tiny plastic tubes are placed in the ears to prevent hearing loss from repeated infections.

The abnormal placement of the eyes and its muscles can sometimes prevent a child from looking straight ahead with both eyes. An ophthalmologist should examine the eyes regularly and correct a muscle imbalance of the eyes with surgery.

An orthodontist (dentist who specializes in correcting misaligned teeth) monitors the teeth because the abnormal jaw structure causes poor development and placement. An oral surgeon may correct the misalignment of the teeth. Proper positioning of the teeth improves speech and facial appearance.

Speech and language delay can result from decreased hearing and an unusual jaw shape. A speech therapist works with the child to develop language skills through simple exercises.

The facial appearance of Apert syndrome can have a devastating emotional effect on the child and family. Support from a psychologist (a specialist in science of the mind) can help the child develop a positive self-image and help parents cope with feelings of guilt. Often parents will blame themselves for a child's condition even they in no way caused it or could have prevented it. The multiple doctors' visits and surgeries can create undue stress as well.

During the many hospitalizations, a pediatric nurse will care for the child. This nurse has received specialized training in the treatment of children with craniofacial disorders. Also, the nurse may introduce the child to the hospital.

Diagnosis of Apert syndrome will usually be made by the geneticist. The family will discuss with the genetic counselor how AS is inherited and the chance for future children to be affected.

Having a child with AS can place a tremendous financial strain on the family. A social worker gives the family important information about medical coverage. This person can also help coordinate medical care and special education services.


Many factors affect the prognosis of a child with AS. The age at which the first surgery takes place to create spaces between the skull bones is important. Mental retardation can result from the buildup of pressure on the brain. Having a supportive, loving family environment increases the chances for normal development. Children with complex medical problems who lack a supportive setting often have delayed mental, social, and emotional development.

Although the hands will never be completely normal, surgeries to separate and straighten the fingers can be done. Tasks such as writing and manipulating buttons will be difficult. Adaptive devices in school and home will allow for more independence. Separation of the toes usually does not improve walking but may improve the child's self image.

Persons with AS who have a normal intelligence level can have full, productive lives. Vocational training will help those with borderline intelligence.



Dufresne, Craig, Benjamin Carson, and James Zinreich. Complex Craniofacial Problems: A Guide to Analysis and Treatment. New York, NY: Churchill Livingston, 1992.

Keene Nancy, Rachel Prentice, and Linda Lamb. Your Child in the Hospital: A Practical Guide for Parents. Cambridge, MA: O'Reilly and Associates, 1996.

Wilson, Golder N., and Carl W. Cooley. Preventive Management of Children With Congenital Anomalies and Syndromes New York, NY: Cambridge University Press, 2000.


Chang, C. C., et al. "Prenatal diagnosis of Apert syndrome." Prenatal Diagnosis 18 (1998): 621-625.

Ferreira, J. C., et al. "Second-trimester molecular prenatal diagnosis of sporadic Apert syndrome following suspicious ultrasound findings." Ultrasound in Obstetrics and Gynecology 14, no. 6 (December 1999): 426-30.

von Gernet, S., et al. "Genotype-phenotype analysis in Apert syndrome suggests opposite effects of the two recurrent mutations on syndactyly and outcome of craniofacial surgery." Clinical Genetics 57 (2000): 137-139.

Wilkie, A. O. M., et al. "Apert syndrome results from localized mutations of FGFR2 and is allelic with Crouzon syndrome." Nature Genetics 9 (1995): 165-172.


Apert Syndrome Support Group. 8708 Kathy, St. Louis, MO 63126. (314) 965-3356.

Children's Craniofacial Association. PO Box 280297, Dallas, TX 75243-4522. (972) 994-9902 or (800) 535-3643. [email protected]. <http://www.ccakids.com>.

National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. <http://www.rarediseases.org>.


FriendshipCenter.com. <http://www.friendshipcenter.com>.

Suzanne M. Carter, MS, CGC