Apert syndrome

What is Apert syndrome?

Apert syndrome is a rare genetic disorder that is identified by craniosynostosis. This is when the joints in a baby’s skull close before they should. Symptoms of Apert syndrome include head and facial deformities, as well as webbed fingers and toes. It occurs in only 1 in 65,000 births.

Causes of Apert syndrome

Apert syndrome, also known as acrocephalosyndactyly, is caused by a gene mutation. The gene affected is the fibroblast growth factor receptor-2, or FGFR2. This gene is responsible for bone growth.

The mutation interrupts proper development of the bones of the skull while the baby is in the womb. The joints, or sutures, of the skull bones close before the brain finishes growing. This results in an abnormal shape of the head as well as irregular bone formations in other parts of the body.

This gene mutation is an autosomal dominant inherited disorder. “Autosomal” means the condition is just as common in men and women. “Dominant” means an abnormal gene only needs to be passed down from one parent to be inherited. There is a 50% chance a child will have Apert syndrome if one parent has the FGFR2 mutation.

Symptoms

Because of craniosynostosis, there are many physical symptoms and characteristics of Apert syndrome. The severity of symptoms depends on which sutures close too soon.

Physical abnormalities may include:

• Acrocephaly – tall, pointed skull

• Prominent forehead

• Hydrocephalus – fluid buildup in the brain

• Soft spot on baby’s head that closes late

• Back of skull that is flat

• Hypertelorism – wide-set eyes

• Exophthalmos – bulging eyes

• Eyes that slant downward

• Flattened nose

• Underdeveloped upper jaw

• Crowding of teeth

• Cleft palate

• Syndactyly – webbed, or fused, fingers or toes

These deformities can affect other parts of the body and cause further issues. These issues may include the following:

• Mild to moderate cognitive and intellectual development. This is due to pressure on the brain from the abnormal shape of the skull.

• Vision problems. These may occur due to an imbalance of the muscles of the eye, as the eyes may be bulging or widely spaced.

• Exposure keratopathy – drying out of the cornea caused by the inability to properly close the eyelids.

• Corneal scarring caused by exposure keratopathy.

• Breathing problems from a flattened nose.

• Ear infections and hearing loss from the malformation of the ears.

Other bones in the body, as well as the skin and organs, can also be affected. Symptoms in these areas of the body can include:

• Slow bone growth in the body leading to a short stature

• Abnormalities of the cervical spine

• Fusion of the arm bones, wrist bones or the vertebrae of the neck

• Hyperactive sweat glands

• Oily skin and acne

• Areas of skin with no hair

• Abnormalities of the heart

• Respiratory issues

Diagnosis

An Apert syndrome diagnosis can sometimes be made before a baby is born. The doctor can perform a 2D or 3D ultrasound or an MRI during pregnancy. These scans check for abnormalities of the skull and syndactyly. The doctor can also perform genetic testing to confirm an FGFR2 gene mutation.

A diagnosis is typically made at birth or in infancy. CT scans or MRIs can find symptoms of craniosynostosis, or other bone deformities. These scans can also identify heart defects.

Differential diagnosis

There are many rare, genetic disorders that present similar symptoms to Apert syndrome.

These syndromes, which also involve craniosynostosis, include:

• Crouzon syndrome – A disorder much like Apert syndrome. What sets it apart is that there is no syndactyly present.

• Carpenter syndrome – A disorder caused by a mutation in the RAB23 or MEGF8 genes. It has the same symptoms as Apert syndrome but is autosomal recessive. This means both parents have to pass the mutation to the child, rather than one parent.

• Pfeiffer syndrome – A syndrome that causes abnormalities in the skull and middle of the face. It also causes wider thumbs and wider big toes. It occurs from a mutation in the FGFR1 and FGFR2 genes.

• Saethre-Chotzen syndrome – A syndrome where the joints in the head fuse unevenly from a mutation in the TWIST 1 gene. Symptoms include wide-set eyes, strabismus (misaligned or crossed eyes), a beak-shaped nose, asymmetrical facial features and syndactyly. 

• Jackson-Weiss syndrome – A disorder that can cause abnormal features of the cranium and also the feet. It typically results from a mutation of the FGFR2 gene. However, this syndrome can also appear from a spontaneous mutation that is not inherited.

• Antley-Bixler syndrome – A disorder caused by mutations in the POR and FGFR2 genes. Symptoms include abnormalities of the bones of the skull and face, fusion of the arm bones, very long, thin fingers and bulging eyes.

• Beare-Stevenson cutis gyrata syndrome – A syndrome that involves abnormalities of the skin and skull from mutations in the FGFR2 gene.

Treatment options

A variety of doctors, surgeons and other medical specialists are often needed to provide a range of treatments for Apert syndrome. Treatment options depend on type and severity of symptoms.

Surgeries are scheduled during particular times of development in order to provide the best outcome. 

Possible procedures include, but are not limited to:

• Cranial surgeries to correct craniosynostosis, drain fluid in the brain and protect brain development

• Reconstructive surgeries to correct abnormalities of the skull, jaw, chin, nose or eyes

• Surgery to separate webbed fingers or toes

• Tarsorrhaphy to protect the corneas

• Surgery to treat heart defects

A team of medical professionals can provide other treatments that may be necessary. That team can include:

• Dentists to care for crowding of teeth and general teeth health

• Otolaryngologists for loss of hearing or breathing issues

• Ophthalmologists to address vision and other eye problems

• Cardiologists for heart problems

• Speech therapists, occupational therapists and physical therapists to provide other helpful modalities

Further visits to the doctor may be needed over time to address symptoms such as sleep apnea and strabismus, which can cause amblyopia (lazy eye).

Prognosis

While there is not a cure, those with Apert syndrome have a full life expectancy. Surgery is important to protect the brain. Ongoing treatment helps with symptoms and possible complications as the patient grows older. Emotional support services from healthcare providers can be of assistance to the family of a loved one with Apert syndrome. And reconstructive surgeries can help those with Apert syndrome live a normal life.

Page published on Wednesday, June 28, 2023

Page updated on Wednesday, July 5, 2023

Medically reviewed on Wednesday, June 7, 2023