Is Craniosynostosis Genetic?

Craniosynostosis is a relatively common congenital disorder, affecting about one in every 2,500 live births. It occurs when the flexible joints in an infant’s skull known as sutures fuse prematurely. This leads to a misshapen head and may cause increased pressure on the brain. The condition is believed to be caused by a combination of environmental and genetic factors.

Different Types of Craniosynostosis

Craniosynostosis is usually considered syndromic (part of a syndrome) or nonsyndromic (not part of a syndrome). Syndromic craniosynostosis is typically caused by a known genetic disorder that likely causes other symptoms as well, while nonsyndromic craniosynostosis is not caused by a known disorder and is often considered a random defect.

The exact cause of craniosynostosis is often unknown, but it's thought to be due to a combination of genetic and environmental factors. Most cases of craniosynostosis are classified as nonsyndromic craniosynostosis. 

Craniosynostosis can also be classified based on which suture is affected. In most cases, a single suture fuses prematurely. In syndromic craniosynostosis, several suture lines may fuse. The four types of craniosynostosis include:

• Sagittal craniosynostosis is the most common type of craniosynostosis, and affects the sagittal suture that runs from the front to the back of the head. It causes a long, narrow head.
• Coronal craniosynostosis affects one or both of the coronal sutures that run from the ear to the top of the head. This type of craniosynostosis causes the forehead to appear flattened and bulging on the affected side.
• Metopic craniosynostosis affects the metopic suture, which runs from the bridge of the nose up to the top of the head. This type of craniosynostosis causes the forehead to look triangular and widens the back of the head.
• Lambdoid craniosynostosis is a rare type of craniosynostosis and affects the lambdoid suture. This suture runs along the back of the head, and premature fusing causes one side of the head to appear flat and one ear to be higher than the other.

Craniosynostosis and Its Genetic Factors

Researchers and physicians have long believed that cases of nonsyndromic craniosynostosis have possible genetic causes. It’s estimated that about 8% of babies with craniosynostosis inherited the condition as part of a genetic disorder.

Researchers believe that a genetic cause of craniosynostosis is passed on to a baby as an autosomal dominant trait. This abnormality in the gene leads to a disruption of the cells responsible for building bones called fibroblasts.

A 2013 study found that a mutation on the fibroblast growth factor receptor (FGFR) genes may contribute to the development of craniosynostosis. The chance of an FGFR gene mutation goes up with paternal age, therefore, the older the father is, the higher the risk of gene mutation in the child. 

When your child has a genetic disorder, it means that the child inherited genes for a particular trait on a chromosome from one or both parents. The risk of passing on an autosomal dominant genetic condition is 50% for each pregnancy. 

Mutations in the following genes may be associated with craniosynostosis:

• TCF-12
• ERF
• CDC45
• SMO
• SMAD6

Some genetic conditions that can cause or include syndromic craniosynostosis are:

• Antley-Bixler is a rare condition that affects the skull and bones in the face.
• Apert syndrome causes premature fusing of the bones in the skull (craniosynostosis), as well as in the fingers and toes.
• Carpenter syndrome causes changes in the formation of the skull, fingers, and toes. 
• Crouzon syndrome affects the bones, muscles, joints, and cartilage. It often leads to the premature fusing of several sutures in the skull.
• Frontonasal dysplasia is a rare disorder that leads to abnormal development of the head and face, including wide-set eyes, a flat nose, and a groove down the middle of the face. 
• Muenke syndrome causes the premature fusing of the coronal suture, as well as other areas of the skull.
• Saethre-Chotzen syndrome causes premature fusing of the bones in the skull and face.
• Pfeiffer syndrome is a rare disorder that causes a baby’s skull bones to fuse together.

Diagnosis of Craniosynostosis

Craniosynostosis is usually diagnosed with a physical exam. Your pediatrician will examine your child’s head, noting any abnormal growth patterns. On your child's scalp, the doctor will look for any prominent veins, which could indicate craniosynostosis. The doctor will also feel along the suture lines, noting any hard ridges. 

Your doctor will feel the soft spots known as fontanelles on your baby’s head. These are usually soft to the touch, but they will feel hard and rigid if a suture has fused. 

Because craniosynostosis can lead to increased pressure around your baby’s brain, your doctor will examine your child for increased intracranial pressure and may recommend a comprehensive eye exam. 

In addition to a physical exam of the child, your doctor will take a thorough history as well. You will be asked questions about your pregnancy, birth experience, and family history. While a diagnosis can be made with a physical exam, your doctor may recommend confirming the diagnosis with computed tomography (CT) scan.

Genetic Testing

If your doctor suspects that your child’s craniosynostosis is part of an underlying genetic disorder, the doctor may order additional lab tests to learn more. Genetic testing may be recommended to evaluate certain genes, including FGFR3, FGFR2, TWIST, and MSX2.

Imaging

The most accurate way to diagnose craniosynostosis is with a CT scan with three-dimensional (3D) reconstruction. This test allows your child’s medical team to see every suture to tell whether they are open or have already fused. A CT scan also shows any abnormalities in the brain. 

Craniosynostosis Treatment

Treatment for craniosynostosis usually involves surgery. Once your child’s skull has begun growing in an abnormal shape, the only way to correct it is with surgery. The goal of surgery is to correct your child’s head shape while ensuring that the brain has enough room to grow. 

The best time to perform craniosynostosis surgery is usually before your child’s first birthday because the bones in their skull are still soft and easier to shape. Surgery may be recommended as early as 1 month old for babies with a severe case of craniosynostosis.

There are two types of surgery that your medical team may discuss with you. Calvarial vault remodeling is usually performed on infants around 6 months old. During this procedure, the surgeon makes an incision in your child’s scalp and then moves the skull bones into a more circular shape. 

The other surgical option, endoscopic craniosynostosis, is less invasive and is usually performed between 2 and 4 months of age. During this procedure, the surgeon makes several tiny incisions in your child’s scalp, then uses a small tube called an endoscope to move the skull bones into a more circular shape.

After endoscopic craniosynostosis, your child will need to wear a molding helmet to ensure that the skull bones continue to grow into the correct shape. 

Complications 

Craniosynostosis is treatable with surgery, especially when it is diagnosed early. It is possible to experience complications from untreated craniosynostosis. 

Possible complications of craniosynostosis include:

• Permanent head or facial abnormalities 
• Developmental delays
• Vision problems
• Seizures
• Breathing problems

Summary

Craniosynostosis can be syndromic or nonsyndromic. Syndromic craniosynostosis is due to a genetic disorder that causes other symptoms as well, while nonsyndromic craniosynostosis is not caused by a genetic disorder. Most cases are nonsyndromic.

Researchers have found that mutations in certain genes are associated with the development of craniosynostosis in your baby. Genetic testing can be performed to evaluate your risk of having a baby with craniosynostosis.

A Word From Verywell

Craniosynostosis is a relatively common congenital condition and has both genetic and environmental causes. Discovering that your child has craniosynostosis can be upsetting, and it is natural to want answers. Learning more about the possible genetic factors may help explain the cause of your child's condition and the odds of having another baby with craniosynostosis in the future. 

Meeting with a genetic counselor may provide additional answers and help you determine your risk in future pregnancies. Talk with your pediatrician if you have questions about your child’s care. 

Frequently Asked Questions

Are there both genetic and environmental factors for craniosynostosis?

Yes, physicians and researchers believe that craniosynostosis is caused by both genetic and environmental factors. Genetic causes include mutations in specific genes. Examples of possible environmental factors include maternal smoking and the use of fertility treatments.

Is genetic counseling recommended for craniosynostosis? 

Sometimes. Once your child is diagnosed with craniosynostosis, your doctor may recommend that you and your family undergo genetic counseling. This process will help you understand your risk factors and the likelihood of having future children with craniosynostosis. This is especially helpful if your child has syndromic craniosynostosis as part of a genetic disorder. 

Which other genetic disorders are associated with craniosynostosis?

Antley-Bixler, Apert syndrome, Carpenter syndrome, Crouzon syndrome, frontonasal dysplasia, Muenke syndrome, Saethre-Chotzen syndrome, and Pfeiffer syndrome are associated with craniosynostosis.