Craniosynostosis

Craniosynostosis is one of the disease groups within ERN CRANIO that covers a wide range of craniosynostosis, both unisutured and multisuture craniosynostosis fall under this group.

What is craniosynostosis?

Craniosynostosis is a condition in which one of more of the cranial sutures close too early. Cranial sutures are required for molding of the head during birth and for rapid growth of the skull in the first few years of life. Too early closure of suture(s) will results in an altered shape of the head and hamper normal growth of the brain.

Craniosynostosis occurs in 1 in 2100 to 1 in 2500 births and may be either non syndromic (also referred to as isolated) or syndromic.

ERN CRANIO endorses the European clinical practice guideline on craniosynostosis, created within the ERN CRANIO network. The guideline describes the treatment and management of craniosynostosis. A patient and family-tailored version of the professional guideline has been developed by one of the ERN CRANIO patient representatives.

Professional guideline

Patient-tailored guideline

The signs of craniosynostosis are usually noticeable at birth, but they'll become more apparent during the first few months of the baby’s life. Signs and severity depend on how many sutures are fused and when in brain development the fusion occurs. These can include:

A misshapen skull, with the shape depending on which of the sutures are affected
An abnormal feeling or disappearing fontanel on the baby's skull
Development of a raised, hard ridge along affected sutures
Slow or no growth of the head as the baby grows

Without treatment, the deformity of the skull will increase and there is a risk of high brain pressure. The chance of this differs per type of skull abnormality. It is also important to test the children for eye abnormalities, hearing abnormalities, general development and breathing problems while sleeping.

Treating craniosynostosis involves surgery to correct the shape of the head and allow for normal brain growth. Early diagnosis and treatment allows adequate space for the brain to grow and develop.

Unisuture craniosynostosis

With unisuture craniosynostosis, 1 of the sutures in the skull has closed prematurely, causing a change in skull shape. It is most often the only congenital disorder and is thus referred to as isolated.

Unilambdoid suture synostosis

Sagittal suture synostosis

Metopic suture synostosis

Unicoronal suture synostosis

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Unilambdoid suture synostosis

The most common form of unilambdoid suture synostosis is non-syndromic.There is a slim chance of an inherited form of unilambdoid suture synostosis. There is also a slim chance that unilambdoid suture synostosis develops in a syndromic form. Individuals that do have a syndromic unilambdoid suture synostosis, develop the unilambdoid suture synostosis due to their other conditions or syndromes.

In lambdoid synostosis, growth of the skull base is also affected, indicated by the ear on that side being located at a lower position, best seen from behind. Moreover, backward growth of the occiput is inhibited on that side, which is accompanied by contralateral occipital bossing. Left lambdoid synostosis can also occur, when the lambdoid suture on the left side of the head closes prematurely. If the left occipital seam is closed then:

The left ear is too low;
The left side of the back of the head is lower;
There is a crookedness in the face that is especially visible when you stand in front of the mirror with your child.

Sagittal suture synostosis

Sagittal suture synostosis can also called scaphocephaly. The most common form of sagittal suture synostosis is non-syndromic or 'isolated', because it's the only condition that your child may have and doesn't occur with any other conditions. There is a very slim chance of an inherited form of sagittal suture synostosis. There is a very slim chance that sagittal suture synostosis develops in a syndromic form. Individuals that do have a syndromic sagittal suture synostosis, develop the sagittal suture synostosis due to their other conditions or syndromes.

Because growth in width is inhibited, the skull grows more and more in length to compensate in the first year of life. The most common form of craniosynostosis is sagittal suture synostosis, where the sagittal suture, running in between the anterior and posterior fontanelle, closes prematurely. The forehead becomes rounder and the back of the head becomes more pointed. A bone ridge can often be felt at the location of the sagittal suture.

A sagittal suture synostosis or 'boat skull' is usually the only congenital condition your child has: this is called an isolated condition. The closure of the sagittal suture has already occurred before birth, around eighteen weeks of pregnancy. Sometimes your child also has other congenital disorders and the boat skull is part of a syndrome. The other conditions can be dental abnormalities, shallow eye sockets that cause the eyes to protrude a little more, or behavioral problems. We can find a genetic cause for these rare syndromic forms of boat skull.

A child with a boat skull has a small chance of mild delays in language and speech development. The intelligence and behavior are the same as the average Dutch children without a boat skull.

A small percentage of children develop increased brain pressure later in life, despite skull surgery. For this reason, annual check-ups by the ophthalmologist are necessary until the age of six.

Consequences for the mother and childbirth
The abnormal skull shape can make it difficult for your child to descend before birth. For this reason, we more often perform caesarean sections when delivering children with a boat skull. Sometimes the diagnosis is already made on the ultrasound at twenty weeks of pregnancy, because the skull has a large circumference and a characteristic shape.

Metopic suture synostosis

Metopic suture synostosis can also called trigonocephaly. The most common form of metopic suture synostosis is non-syndromic. There is a very slim chance that metopic suture synostosis develops in a syndromic form. Individuals that do have a syndromic metopic suture synostosis, develop the metopic suture synostosis due to their other conditions or syndromes.

In children where the metopic or ' forehead' suture closes too early, the forehead cannot grow in width, but the rear part of the skull continues to grow. The forehead is therefore pointed, the eyes are close together and the outer corners of the eyes are higher than the inner corners. A bone ridge can often be felt at the location of the forehead seam. That is why we also call this condition 'wedge skull'. Only a severe wedge skull has these characteristics. A prominent vertical ridge over the metopic suture is palpated in the midline.

The condition can range from mild to severe. In contrast to the other types of craniosynostosis, the risk of increased cerebral pressure (which we determine through ophthalmology) in trigonocephaly is very low. That is why we are increasingly reluctant to operate. It also happens that the abnormal shape of the forehead improves spontaneously, so that surgery is no longer necessary as a matter of course

In children with a mild form, the forehead has a normal width and a bone ridge can be felt and seen at the location of the forehead seam. This is caused by the normal closure of the cranial suture in the first months of the child's life. This form does not require surgery. The ridge in the forehead will naturally diminish over the years.

In the moderate form of wedge skull, the forehead is narrow and there is also a bone ridge. In addition, the forehead is slightly pointed. This usually improves on its own. It is safe to wait for this improvement.

Children with a severe form of wedge skull also have a very low risk of increased cerebral pressure. It is not yet possible to say with certainty to what extent spontaneous improvement in the shape of the forehead occurs. We are conducting research into this. We use an MRI scan to examine whether the blood flow to the brain is normal. If the results of the MRI scan and eye examination are good, there is no reason to operate. The brain can then develop normally. The ophthalmologist will check your child every year for signs of increased cerebral pressure. If the forehead does not improve sufficiently over time, we may still decide to perform surgery in consultation with you.

The sooner the forehead seam closes, the more abnormal the shape of the forehead is. The severe point shape occurs when the child's anterior suture closes before birth, around fifteen weeks of pregnancy. The mild form occurs when the forehead seam closes just before or after birth. The moderate form is in between. The cause is usually unknown, but it is thought that it's a combination between environmental factors and genes. Certain medications or genetic abnormalities can sometimes be the cause.

Some children with a wedge skull appear to have behavioral abnormalities that are associated with developmental delay. We can only test this reliably when your child is about three years old. We will offer this examination to you as standard around that age, but you can also have the examination done at a later age. The research is conducted at the Department of Child and Adolescent Psychiatry and Psychology. If we recommend treating your child, this can often be done in your own region. The developmental delay may be caused by a genetic abnormality. Whether or not surgery of the skull has no influence on the development of your child.

Children with a true wedge skull often have farsightedness, which requires glasses. The ophthalmologist will test your child for this.

Unicoronal suture synostosis

Unilambdoid suture synostosis can also called plagiocephaly. The most common form of unicoronal suture synostosis is non-syndromic,and its cause is unknown. The chance exists that unicoronal suture synostosis is inherited by one of the parents. There is a slim chance that unicoronal suture synostosis develops in a syndromic form. Individuals that do have a syndromic unicoronal suture synostosis, develop the unicoronal suture synostosis due to their other conditions or syndromes.

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In unicoronal synostosis, growth of the skull base is affected, indicated by the ear on that side being located at a lower position, best seen from behind. Moreover, backward growth of the occiput is inhibited on that side, which is accompanied by contralateral occipital bossing. Left unicoronal synostosis can also occur, when the coronal suture on the left side of the head closes prematurely.

If the left crown seam is closed:

The left eye socket is too high
Is the left side of the forehead towards the front;
The eye opening is larger on the left than on the right
the nose is slightly crooked.

Unilateral closure of a coronal suture may be the only congenital condition. There is also a chance that it is part of several congenital conditions, also called a syndrome. The other conditions may include hearing loss, webbed fingers or toes, a low-hanging eyelid or short height.

We can make the distinction through DNA research. Children with a crooked skull without a demonstrable genetic cause have a slightly higher risk of behavioral problems or developmental delays. The chance of increased brain pressure developing after skull surgery is small. For that reason, a single operation is usually sufficient.

Multisuture
craniosynostosis

In multisuture craniosynostosis, two or more cranial sutures have closed too early. Craniosynostosis is referred to as syndromic if other congenital disorders are present, such as disorders of the face, hands and feet, but may also involve other organs, for instance heart disorders or anorectal anomalies.

When two or more skull sutures close too early, the skull can no longer grow in that location. In a place where there is still space, the skull grows more. How many and which seams close too early determines what the shape of the skull looks like. Without proper treatment there is a high risk of high cerebral pressure. This causes the brain to work less well. In syndromic craniosynostosis, in addition to the closure of the cranial sutures, other congenital abnormalities also occur. For example, on the hands and feet, the eyes and eyelids, the upper jaw and teeth, the auricles and hearing.

Breathing can be somewhat difficult while sleeping, which causes snoring. We measure the severity of breathing problems with a sleep study.

The characteristics of premature closure of multiple cranial sutures vary greatly and can vary from mild to severe deformity of the skull and face. The most well-known types of syndromic craniosynostosis are:

We describe the lesser-known types of syndromic craniosynostosis under 'other syndromic craniosynostosis'. For example: carpenter syndrome, IL11RA syndrome, ERF syndrome, and HUWE1 syndrome. We use genetic testing to determine the genetic causes of syndromic craniosyntosis. These include changes in the genes FGFR2, FGFR3 and TWIST1. The specific genetic cause largely determines what the associated congenital conditions are, in addition to the deformity of the skull and face. More information about this is described in the specific syndromes.

Apert syndrome

Courzon/Pfeiffer syndrome

Muenke syndrome

Seathre-Chotzen syndrome

Craniofrontonasal syndrome

TCF12 syndrome

Bicoronal suture synostosis

Mercedez-Benz synostosis

Other forms syndromic craniosynostosis

The cause of syndromic craniosyntosis is a genetic change. This may have arisen in the child before birth. But it is also possible that the genetic change is present in one of the parents and has been passed on to the child in this way.

The clinical geneticist carries out the genetic tests and tells you whether you as a parent have a genetic change, or whether this has occurred in your child.

The symptoms and consequences depend on the number and size of the skull sutures that grow together. The eyes may be wide apart or protruding, sometimes the ears are not at the same height and there may be abnormalities in the nose, mouth or pharynx.

Without surgery, the abnormal shape of the skull and face will increase. The risk of increased brain pressure is therefore greater, especially from the age of twelve months. Due to the increased brain pressure, the brain sometimes works less well. This has consequences for your child's speech and movement, for example.

Bicoronal suture synostosis

Characteristic findings are:

Retrusion of forehead and supraorbital rim on both sides
Broad skull
No other congenital anomalies are present
No genetic cause of the craniosynostosis is detected

Mercedez-Benz synostosis

With this condition, a fusion of both the lambdoid and sagittal suture has taken place. Characteristic findings of this condition are:

Prominent and wide forehead (bossing of the forehead)
Restricted occiput
Low position of both ears

Apert syndrome

In Apert syndrome the skull shape is broad. The eye sockets are shallow, making the eyes more forward. The eyes may move abnormally because the muscles are not properly developed. The eye sockets may also be far apart.

The midface does not grow forward enough and the upper jaw is narrow, leaving little room for teeth and molars. The teeth often erupt late. Breathing may be difficult while sleeping, causing the child to snore or stop breathing for a short time. Ear infections occur more often. Severe acne can develop during puberty. Intelligence varies from normal to very low. Abnormalities that occur less often are: cleft palate, heart and kidney abnormality, and abnormalities of cervical vertebrae and joints.

Without surgery, the abnormal shape of the forehead will increase. The risk of increased brain pressure is high, especially from the age of twelve months. The high cerebral pressure can be the result of a skull that is too small, too much cerebrospinal fluid or breathing problems.

The breathing problems do not improve without treatment. Sleeping in a side or prone position can make breathing easier and prevent flattening of the back of the head. Closing a cleft palate can even worsen breathing problems.

The upper jaw hardly grows, so the difference with the lower jaw is increasing.

Orthodontic care is necessary for good oral hygiene and the position of the teeth.

Walking can become painful due to foot and hip abnormalities.

Crouzon or Pfeiffer syndrome

Crouzon syndrome involves premature closure of the cranial sutures. The midface is set back and the eyes are far forward (“convex eyes”). Breathing is often audible while sleeping. The fontanel may feel tense.

In Crouzon syndrome, the skull shape can be abnormal or normal, depending on the cranial sutures involved. Brain abnormalities can include: high cerebral pressure, too much cerebrospinal fluid and too low position of parts of the cerebellum. The eye sockets are shallow, making the eyes more forward. The eyes may move abnormally because the muscles are not properly developed. The eye sockets may also be far apart.

The midface does not grow forward enough and the upper jaw is narrow, leaving little room for teeth and molars. The teeth often erupt late. Breathing may be difficult while sleeping, causing your child to snore or stop breathing for a short time. Ear infections occur more often. Average intelligence is normal but varies from low to high.

Crouzon syndrome is usually caused by a genetic abnormality of the FGFR2 gene. Abnormalities in the FGFR1 or FGF3 gene can also cause Crouzon syndrome. This genetic abnormality usually arises during the development of the child, or comes from one of the parents. If one parent has Crouzon syndrome, there is a 50% chance of passing it on to their child. If the abnormality is in the FGFR3 gene, the child also has a skin condition in which the skin is dark in color in some places and feels rough to the touch (acanthosis nigricans). This skin condition usually becomes more visible with age.

Pfeiffer syndrome is actually another name for the same syndrome. Before the genetic causes became known, a distinction was made between Crouzon and Pfeiffer syndrome on the basis of abnormalities in the thumbs and big toes. If they were wide and short, it was called glandular fever syndrome. Because Crouzon and Pfeiffer syndrome appear to have the same genetic causes, we no longer make this difference.

The severity of the syndrome can vary greatly: it can be very mild or very severe. For the severe form, some doctors still use the name Pfeiffer syndrome.

Without surgery, the risk of increased cerebral pressure will increase, especially from the age of twelve months. The high cerebral pressure can be the result of a skull that is too small, too much cerebrospinal fluid or breathing problems. The low position of parts of the cerebellum can cause complaints of the nerve pathways, which, for example, makes walking less easy or changes the feeling in the hands.

To detect this, we occasionally make MRI scans of the brain. The breathing problems do not improve without treatment. Sleeping in a side or prone position can make breathing easier. The upper jaw hardly grows, so the difference with the lower jaw is increasing. Orthodontic care is necessary for good oral hygiene and the position of the teeth.

Muenke syndrome

Muenke syndrome is characterized by the premature closure of one (crooked forehead) or both coronal sutures (broad skull) and hearing loss.

Characteristics of this condition are:

The skull shape is determined by the premature closure of one or both coronal sutures (crooked skull or wide skull)
The mouth is small with a high and narrow palate. The upper jaw can be narrow, leaving little space for all the teeth.
There is hearing loss due to a defect in the inner ear.
Intelligence is almost normal.
Behavioral abnormalities such as ADHD and autism-like disorders are more than twice as common as in peers.
Breathing may be somewhat difficult while sleeping, causing the child to snore, for example. We measure the severity of breathing problems with a sleep study.

Muenke syndrome results from a genetic abnormality known as FGFR3 Pro250Arg. If one parent has this genetic disorder, there is a 50% chance that it will be passed on to their child. The genetic abnormality may also have arisen for the first time in their child. There is then no increased risk for the parents of a subsequent child with Muenke syndrome.Family members with the same genetic abnormality may differ in the characteristics of the syndrome: one or both coronary sutures may have closed too early and sometimes other cranial sutures also close too early. The features can be mildly visible or very obvious. Someone can also be a carrier of the genetic abnormality without having any characteristics; They therefore do not have premature closure of the cranial sutures, but they often have a somewhat large skull and hearing loss.

Craniofrontonasal syndrome

Too early closure of one or both coronal sutures (crooked or wide skull) and a wide nasal tip. The thumbs and big toes are broad or double. Often the chest is asymmetrical and there is a short neck.

Characteristics of this condition are:

The skull shape is crooked or broad.
The eyes may move abnormally because the muscles are not well developed. The eye sockets may also be far apart.
The nasal tip is broad or split (dimple in the middle).
The upper jaw is narrow, leaving little room for teeth and molars.
The teeth often erupt late.
The thumbs and big toes are broad or even double. The nails are often friable with ridges.
The chest is skewed and the breast development can also be asymmetrical.

How often does it happen?
In the Netherlands, approximately one to two children per year are born with craniofrontonasal syndrome.

Saethre-Chotzen syndrome

The Saethre-Chotzen syndrome is characterized by premature closure of one (crooked forehead) or both coronal seams (wide skull) and the low hanging of one or both upper eyelids. The body length is short. The hands have webbed feet, one handline and short fingers.

The skull shape is determined by the premature closure of one or both coronal sutures (see crooked skull or wide skull). One or both upper eyelids hang too low and can obscure the pupil, making vision difficult. The upper jaw can be narrow, leaving little space for all the teeth. Less common abnormalities are: an abnormal location of the anus, umbilical hernia, cervical vertebral abnormalities, deafness, developmental delay. Breathing may be somewhat difficult while sleeping, causing the child to snore, for example. We measure the severity of breathing problems with a sleep study. The children may have a somewhat short body size.

Saethre-Chotzen syndrome is the result of a genetic abnormality in the TWIST1 gene. If one of the parents has this genetic abnormality, there is a 50% chance that it will be passed on to the next child. The genetic abnormality may also have arisen for the first time in the child. There is then no increased risk for the parents of a subsequent child with Saethre-Chotzen syndrome. Family members with the same genetic abnormality may differ in the characteristics of the syndrome: one or both coronary sutures may have closed too early and sometimes other cranial sutures also close too early. The features can be mildly visible or very obvious.

We distinguish between a small change (mutation) in the TWST1 gene and the absence of a piece (deletion) of the TWIST1 gene. If a piece of this gene is missing, the risk of developmental delay appears to be greater.

TCF12 syndrome

Characteristic is the premature closure of one (crooked forehead) or both coronal sutures (broad skull). In exceptional cases, other cranial sutures may also have closed too early.

The skull shape is determined by the premature closure of one or both coronal sutures (see crooked skull or wide skull). The upper jaw can be narrow, leaving little space for all the teeth. Because the genetic abnormalities in the TCF12 gene have only recently been discovered, not much is known about the associated symptoms. Our team conducts scientific research into this.

The TCF12 syndrome is the result of a genetic abnormality in the TCF12 gene. If one of the parents has this genetic abnormality, there is a 50% chance that it will be passed on to the next child. The genetic abnormality may also have arisen for the first time in the child. There is then no increased risk for the parents of a subsequent child with TCF12 syndrome. Family members with the same genetic abnormality may differ in the characteristics of the syndrome: one or both coronary sutures may have closed too early and sometimes other cranial sutures also close too early. The features can be mildly visible or very obvious.

Someone can also be a carrier of the genetic abnormality without having any characteristics; they therefore do not have premature closure of the cranial sutures.

Other syndromic
craniosynostosis syndromes

In other craniosynostosis syndromes, premature closure of two or more cranial sutures occurs, for which a genetic cause has been found. The syndrome is usually very rare or only recently known, so there is less information about it.

The premature closure of two or more cranial sutures determines the shape of the skull. Without proper treatment there is a high risk of excessive brain pressure. Other congenital abnormalities may also occur. We can increasingly find the genetic cause for this, but that is not always the case. To better recognize the cause, our team conducts a lot of research into this.

The characteristics of premature closure of multiple cranial sutures vary greatly, depending on which sutures are involved and which genetic cause we find. With special genetic tests we discover new genetic causes. These include changes in the genes RAB23, IL11RA, HUWE1 and ERF. It may be necessary to test the DNA of your child and both parents to find the cause. Our team conducts scientific research into the genetic causes in collaboration with other craniofacial teams in Europe.

RAB23 (carpenter syndrome):
Closure of sagittal and metopic seams, too many fingers or toes that are partly fused together, umbilical hernia, undescended testis, obesity, developmental delay. Carpenter syndrome can also be caused by an error in the MEGF8 gene. In addition to the above symptoms, these children are at risk of abnormalities of the heart and large blood vessels.
IL11RA:
Closure of cranial sutures usually in the first year of life, less forward growth of the upper jaw, dental abnormalities, hearing loss.
HUWE1:
Multiple seam closure, developmental delay, speech-language delay, scoliosis, short height.
PROPERTY:
Closure of multiple sutures usually in the first year of life, eyes set far apart, speech-language delay, hyperactivity, moderate gross motor skills, poor concentration.

Craniosynostosis

What is craniosynostosis?

Unisuture craniosynostosis

Unilambdoid suture synostosis

Sagittal suture synostosis

Metopic suture synostosis

Unicoronal suture synostosis

Multisuture craniosynostosis

Bicoronal suture synostosis

Mercedez-Benz synostosis

Apert syndrome

Crouzon or Pfeiffer syndrome

Muenke syndrome

Craniofrontonasal syndrome

Saethre-Chotzen syndrome

TCF12 syndrome

Other syndromic craniosynostosis syndromes

Multisuture
craniosynostosis

Other syndromic
craniosynostosis syndromes