What Are Craniosynostosis Syndromes?

Craniosynostosis syndromes, or syndromic craniosynostosis, are conditions in which premature fusion of one or more of the baby's cranial sutures occurs in the womb or shortly after birth. There are around 200 known craniosynostosis syndromes. These syndromes are differentiated by the suture type and the gene mutation causes.

Craniosynostosis syndromes either occur by chance, with no explanation, or are caused by genetic abnormalities. If left untreated, the abnormally shaped skull that results from craniosynostosis can cause neurologic, visual, and respiratory problems.

Keep reading to learn more about these syndromes, including the most common types, symptoms, causes, treatment, and more.

Types of Craniosynostosis Syndromes

Cranial sutures are joints made of strong, fibrous tissues that hold together the large, flat bones of the baby’s skull. These sutures meet at the fontanels, the soft areas of the baby’s head. Cranial sutures remain flexible during infancy so that the skull can expand as the brain grows.

If the cranial sutures fuse too early (craniosynostosis), the child’s brain cannot grow. This will eventually lead to brain damage. The most common craniosynostosis syndromes are Crouzon, Apert, and Pfeiffer syndromes.

Crouzon syndrome affects 16 births out of 1 million. It is caused by mutations of the fibroblast growth factor receptor (FGFR) genes, specifically the FGFR2 gene. The condition is inherited in an autosomal dominant manner.

Apert syndrome occurs in 6–15 births out of 1 million. Much like Crouzon syndrome, it is caused by mutations of the FGFR2 gene. It is also caused by an autosomal dominant inheritance pattern.

Pfeiffer syndrome affects one in 1 million live births. It is caused by mutations of the FGFR1 and FGFR2 and inherited in an autosomal dominant manner.

Syndromic Craniosynostosis Symptoms

The signs of syndromic craniosynostosis are usually present at birth and will become more apparent during the first few months of life. Signs and symptoms will depend on how many sutures are fused and during which part of brain development the fusion happened.

Commons features of many craniosynostosis syndromes are:

• Skull and midface deformities
• Wide-set or bulging eyes
• A depressed nasal deformity
• A cloverleaf skull anomaly (a tri-lobar skull shape that looks like a cloverleaf, accompanied by a high forehead, prominent and wide-spaced eyes, and low-set ears)

Additional symptoms are specific to the type of craniosynostosis syndrome.

Crouzon Syndrome

In addition to the general symptoms of craniosynostosis, babies with Crouzon syndrome might also experience these symptoms:

• Strabismus (crossed eyes)
• Short and wide head or a long and narrow one
• Enlarged forehead
• Vision loss
• Slanted eyelids
• Flattened cheeks
• Curved, beak-like nose
• Small and poorly formed upper jaw and a protruding lower jaw
• Hearing loss
• Cleft lip (opening in the lip) or a cleft palate (opening of the roof of the mouth)
• Crowded teeth and/or mismatched bite
• Hydrocephalus: A condition in which there is impaired blood flow or impaired absorption of the fluid circulating through the ventricles of the brain and spinal canal leading to increased fluid on the skull, affecting up to 30% of people with Crouzon syndrome
• Acanthosis nigricans: A skin condition causing dark, thick, velvety patches of skin to form in areas where the skin folds (such as at the armpits, the front of the neck, and behind the knees), experienced by a small percentage of children with Crouzon syndrome

Apert Syndrome

Apert syndrome is known to cause deformities of the skull, face, and limbs.

Symptoms might include:

• A tall skull and high forehead
• An underdeveloped jaw, including dental problems—missing and crowded teeth and irregular enamel
• Small nose
• Fused or webbed fingers or toes (syndactyly)
• Midfacial hypoplasia (decreased growth in the central part of the face leading to a sunken facial appearance)
• Slower mental development resulting from the abnormal skull growth
• Cleft palate
• Vision problems
• Recurrent ear infections
• Hearing loss
• Breathing problems from having a small nose and small airway passages
• Hyperactive sweat glands
• Severe acne, especially during puberty
• Missing hair in the eyebrows

Pfeiffer Syndrome

Pfeiffer syndrome appears in three types:

• Type 1 is the mildest and the most common. People with Type 1 have normal intelligence and a normal lifespan.
• Type 2 causes severe neurological problems and a cloverleaf deformity.
• Type 3 is similar to type 2 but without the cloverleaf deformity.

Babies born with Pfeiffer syndrome may have the following symptoms:

• Abnormal growth of the skull bones, leading to bulging and wide-set eyes, a high forehead, an underdeveloped jaw, and a beaked nose
• Broad thumbs and big toes that are offset from the other fingers and toes
• Hearing loss
• Syndactyly or fingers and toes that appear shorter than normal
• Sleep apnea (when breathing stops and starts during sleep) from nasal airway blockages

Causes

Each of the syndromes linked to craniosynostosis is caused by a mutated gene, specifically GFR2, FGFR3, FGFR1, TWIST1, and EFNB1 genes. These mutated genes can be inherited from one parent or can occur spontaneously.

Apert, Pfeiffer, and Crouzon syndromes are caused by FGFR genes and inherited through an autosomal dominant pattern. Most craniosynostosis syndromes are inherited in an autosomal dominant pattern, but some others are autosomal recessive and X-linked dominant inherited patterns.

While most X-linked disorders affect males more than females, craniofrontonasal syndrome (CFNS) affects females more severely. Males with the condition show as asymptomatic (no symptoms) or with milder forms of the condition.

CFNS is a rare type of craniosynostosis that causes premature closure of some of the bones of the skull during development that affect the shape and appearance of the head and face. The condition is named for the parts of the head and face affected: skull (cranio), face (fronto), and nose (nasal).

Researchers are yet to identify every gene that causes a type of craniosynostosis syndrome. But they are continuing to find new genes.

Diagnosis

Craniosynostosis syndromes are distinguishable early because of the symptoms in the skull, face, and in some cases, the hands, thumbs, and big toes.

Because skull deformities are similar among many of these syndromes, your child’s doctor will use other testing methods to get an accurate diagnosis. They will also involve other specialists in their evaluations, such as a pediatric neurosurgeon or plastic and reconstructive surgery specialists.

Testing methods for craniosynostosis include a physical exam, imaging studies, and genetic testing.

• Physical exam: During the physical exam, the healthcare professional will feel the baby’s head for abnormalities, including suture ridges and facial deformities.
• Imaging: Computerized tomography (CT) or magnetic resonance imaging (MRI) scans can show whether sutures have fused. Fused areas of the skull are identifiable by their absence—sutures are no longer present once they have fused, and there may be ridging at the suture lines.
• Genetic testing: Genetic testing may be done to determine the type of craniosynostosis syndrome.

Treatment

Craniosynostosis syndromes need to be diagnosed and treated as early as possible. Treatment will be determined by a child’s doctor and based on:

• The child’s age, overall health, and medical history
• The extent and severity of the syndrome
• Which sutures are involved—sagittal, coronal, metopic, or lambdoid
• Your child’s ability to take certain medicines or tolerate certain procedures and therapies
• Your preferences for your child

Surgery is typically recommended to treat craniosynostosis. It can reduce pressure on the skull and correct deformities of the skull and face. Surgical options might include endoscopic craniectomy or cranial vault remodeling, which are:

• Endoscopic craniectomy is a minimally invasive procedure in which the surgeon opens the affected sutures to help the baby’s brain grow normally.
• Cranial vault remodeling is an open procedure to reshape and replace bone to allow for improved head shape and increased room for the developing brain.

Surgery can also be done to correct webbing or any jaw problems, including crowded teeth.

It is also important to evaluate a child with craniosynostosis for other problems that can occur down the road and treat those as they occur.

Additional problems linked to craniosynostosis that need treatment might include:

• Breathing problems
• Eye symptoms, especially if the eyelids don’t properly protect the eyes
• Hearing loss
• Speech and language problems: Evaluations need to be done to determine if a child’s development is on track.

Timeline

Early consultation with specialists is crucial for a child who has syndromic craniosynostosis. It is best to operate before a child has reached their second birthday, when the bones of the skull are still very soft and easy to operate on.

If your child’s condition is severe, the pediatric surgeon might recommend the surgery as early as 1 month of age.

After surgery to repair skull abnormalities, your child’s doctor might recommend helmet therapy to help shape the baby's skull. The surgeon will determine how long the baby will need helmet therapy based on how quickly the head shape responds to treatment. Helmet therapy is more common after endoscopic cranial surgery.

In addition to surgical treatment for skull abnormalities, a midface advancement procedure might be done. This procedure involves bringing the cheekbones and upper jaw forward to better protect the eyes and improve the child’s airway.

Children with upper jaw abnormalities may also need orthodontic treatment to correct an underbite or severely crowded teeth. An underbite means the lower teeth extend farther than your upper teeth. Treatment of dental problems might include a combination of braces and surgical treatment.

Timing for midface surgery and orthodontic treatment might be early in the child's life or after growth has been completed—depending on the needs of the child, the severity of symptoms, and the overall health of the child.

Children with Apert Syndrome who have webbing of the hands and feet will need surgery early to improve their mobility and functioning. A surgeon can also correct additional deformities of the fingers, toes, and limbs.

Prognosis

It is very possible for a child who has had surgery to open up fused sutures to eventually have a normally shaped head and normal brain development. Many kids who have surgery early won’t experience any cognitive delays or complications related to their skull abnormalities.

The recovery process with a craniosynostosis condition is different for each child. Your child’s surgeon will give you instructions on how to care for your child at home and how to manage any other problems that might need urgent medical care.

Your child will also need frequent medical evaluations to make sure the skull, facial bones, jaw, and brain are developing normally. Your child’s medical team will also provide you with information on how to best help your child and what additional care they will need.

Summary

In craniosynostosis syndromes, one or more cranial sutures of the skull fuses prematurely in a fetus or infant. As a result, the brain does not have room to grow. This can cause many problems.

The three most common types are Crouzon, Apert, and Pfeiffer syndromes. These syndromes can be due to genetic abnormalities or may occur for unknown reasons. Surgical treatment and supportive therapy can allow better outcomes.

A Word From Verywell

Learning that your baby has a craniosynostosis syndrome might cause a range of emotions, including anger, fear, and worry. You may not know what to expect, and you may worry about your ability to care for your child. The best way to reduce fear and worry is through education and support.

Many medical centers with craniofacial specialty teams can be valuable resources for information about your child’s condition, care, and treatment options. Ask your child’s medical team about support groups in your community or how to reach out to other families who have dealt with syndromic craniosynostosis.

Your child’s future can be bright. Many children who have surgery to manage craniosynostosis have normal cognitive development and good cosmetic results from the surgery. Early diagnosis and treatment are vital, as are early interventions for children who experience developmental delays or intellectual disabilities.

Frequently Asked Questions

What is syndromic craniosynostosis?

Syndromic craniosynostosis refers to conditions in which the sutures in a baby’s skull close too early. This might occur in the womb or shortly after birth. There are more than 200 craniosynostosis syndromes that are a result of sporadic or inherited mutated genes.

Each syndrome has special characteristics, but many share common features, including skull and midface deformities, wide-set or bulging eyes, a depressed nasal bridge, and a cloverleaf skull deformity (high forehead, prominent wide-spaced eyes, and low set ears).

Who is at risk of craniosynostosis?

The causes of craniosynostosis in most babies are unknown. Many of the conditions related to craniosynostosis are the result of changes in the genes.

Sometimes, a single gene is abnormal. In other cases, these syndromes are thought to be caused by a combination of genes and other factors—such as things the pregnant person is exposed to during pregnancy, or what they eat or drink, or any medicines they take while pregnant.

How common is craniosynostosis?

Craniosynostosis is believed to occur in one out of every 2,100 to 2,500 live births. Different suture types are affected, with the sagittal suture most commonly affected—up to 55% of the time. This suture runs from the front of the head to the back of the head.

Syndromic craniosynostosis is hereditary and accounts for 15%–30% of craniosynostosis cases. Specific single-gene mutations or chromosomal abnormalities can be identified in about 20% of syndromic craniosynostosis.

What should you expect after craniosynostosis surgery?

Children who undergo minimally invasive surgery typically are sent home the next day and given pain medications. The child will need to wear a special helmet up to 23 hours a day for several months.

Children who have an open cranial vault remodeling surgery will need to be in the hospital for a few nights. Any plates or screws used to hold the skull together will dissolve within months. The bones should heal within a few weeks after the surgery. Your child will need to be seen annually by the surgeons until the child is done growing.