Craniosynostosis is a condition in which one or more of the fibrous sutures in a young infant's skull prematurely fuses by turning into bone (ossification), thereby changing the growth pattern of the skull. Because the skull cannot expand perpendicular to the fused suture, it compensates by growing more in the direction parallel to the closed sutures.

Craniosynostosis occurs in one in 2000 births.

Craniosynostosis is part of a syndrome in 15% to 40% of affected patients, but it usually occurs as an isolated condition. The term is from cranio, cranium; + syn, together; + ost, relating to bone; + osis, denoting a condition. Craniosynostosis is the opposite of metopism.

Signs and symptoms

thumbnail|Kinds of craniosynostosis

Children born with craniosynostosis have a distinct phenotype, i.e., appearance—observable traits caused by the expression of a condition's genes. The features of craniosynostosis' particular phenotype are determined by which suture is closed. The fusion of this suture causes a certain change in the shape of the skull; a deformity of the skull. Using this law, the pattern of skull deformity in craniosynostosis often may be predicted.

Premature sagittal suture closure restricts growth in a perpendicular plane, thus the head will not grow sideways and will remain narrow. This is best seen in a view standing above the child looking downward at the top of the head. The condition is four times more common in boys than in girls.

Trigonocephaly

Trigonocephaly is a result from the premature closure of the metopic suture.

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Anterior plagiocephaly is a clinical description of unilateral coronal synostosis.

Posterior plagiocephaly

Unilateral lambdoid synostosis is also called posterior plagiocephaly, indicating that this gives, just like unilateral coronal synostosis, a 'skew head'. The difference is that this time, the deformity mostly shows at the occiput.

By Virchow's law, restriction of growth will occur at the ipsilateral side of the head; compensatory growth will occur at the contralateral side of the head. This growth pattern exerts an effect at the base of the skull, which is not even when the child is assessed from a point of view standing behind the child, as well as on the cervical spine, which shows a curvature. In addition, from a point of view standing behind the child, a bulging of the mastoid can be seen. In general practice, the term is used to describe the children with three or more cranial sutures closed.

Kleeblattschädel is a feature of several conditions and can also be seen in nonsyndromic manifestations. True pansynostosis can also be nonsyndromic but is also seen in two conditions: ERF-related craniosynostosis and Robinow-Sorauf syndrome (now considered a form of Saethre-Chotzen syndrome).

Other forms

  • Apert syndrome: an abnormal skull shape, small upper jaw, and fusion of the fingers and toes.
  • Baller-Gerold syndrome: craniosynostosis with radial aplasia.
  • Beare-Stevenson syndrome: craniosynostosis with cutis gyrata, acanthosis nigricans, and digit anomalies.
  • Carpenter syndrome: acrocephaly with variable synostosis of the sagittal, lambdoid, and coronal sutures; peculiar facies, brachydactyly and syndactyly, foot polydactyly.
  • Crouzon syndrome: craniofacial abnormalities with bilateral coronal suture fusion; anterior and posterior of skull shortness, flat cheek bones and a flat nose.
  • Jackson-Weiss syndrome: craniosynostosis with midfacial hypoplasia and foot anomalies.
  • Muenke syndrome: coronal craniosynostosis (plagiocephaly and brachycephaly), short feet and palms, hearing impairment, hypertelorism, and proptosis.
  • Pfeiffer syndrome: abnormalities of the skull, hands, and feet; wide-set, bulging eyes, an underdeveloped upper jaw, beaked nose.
  • Saethre–Chotzen syndrome: short or broad head; the eyes may be spaced wide apart and have palpebral ptosis (droopy eyelids), and fingers maybe abnormally short and webbed.
  • Shprintzen-Goldberg syndrome: craniosynostosis with marfanoid habitus and tissue anomalies.<gallery>

File:Précis de psychiatrie 3.jpg|alt=|Apert syndrome

File:Carpenter Syndrome 1.jpg|Carpenter syndrome

File:Patient with Crouzon syndrome (1912).jpg|alt=|Crouzon syndrome

File:Osseous Deformity Case 1.jpg|Muenke syndrome

File:Girl aged 17 years with marked proptosis Wellcome L0062481.jpg|alt=|Pfeiffer syndrome

File:Pyrgocephalus.jpg|Saethre-Chotzen syndrome

</gallery>

Complications

Not all cranial abnormalities seen in children with craniosynostosis are solely a consequence of the premature fusion of a cranial suture. This is especially true in the cases with syndromic craniosynostosis. Findings include elevation of the intracranial pressure; obstructive sleep apnea (OSA); abnormalities in the skull base and neurobehavioral impairment.

The main risks of prolonged elevated intracranial pressure may include cognitive impairment and impaired vision through prolonged papilledema These are the main reasons why fundoscopy should be performed during the physical examination of children with craniosynostosis. The Monro-Kellie doctrine reduces the cranial vault to a box with rigid walls. The response involves vasodilatation of the cranial vault blood vessels, increasing the volume of one of the elements in the Monro-Kellie doctrine.

Ventriculomegaly is a usual finding in children with the Apert syndrome.

Neurobehavioural impairment

Neurobehavioural impairment includes problems with attention and planning, processing speed, visual spatial skills, language, reading and spelling. Sox9, Slug, Osteocalcin, growth factors and multiple Collagen type genes are upregulated in this coordinated and specific sequence (see Figure). Despite the progress that has been made, many things are still not understood about the suture biology and the exact causative pathways remain yet to be completely understood.

Multiple potential causes of premature suture closure have been identified, such as the several genetic mutations that are associated with syndromic craniosynostosis.

Most likely, a role is played by biomechanical factors, as well as environmental, hormonal and genetical factors. It has been found by Jacob et al. that constraint inside the womb is associated with decreased expression of Indian hedgehog protein and noggin. These last two are both important factors influencing bone development.

On the other hand, a recent evaluation of valproic acid (an anti-epilepticum), which has been implicated as a causative agent, has shown no association with craniosynostosis.

Certain medication (like amine-containing drugs) can increase the risk of craniosynostosis when taken during pregnancy, these are so-called teratogenic factors. It is thought that the bone matures faster due to high levels of thyroid hormone. This finding is highly suggestive of a genetic cause, which has possibly been found in the fibroblast growth factor receptor 3 (FGFR3) and TWIST genes.

In terms of syndromic craniosynostosis not only do FGFR3 and TWIST genes feature, but also FGFR1 and in particular FGFR2, which has been reported in 90% of the syndromic craniosynostoses such as Apert, Crouzon, Peiffer and Jackson–Weiss. The mutations can be divided into mutations that lead to gain of function (in FGFR genes) and mutations that lead to loss of function (in TWIST genes). In the nonsyndromic cases, a positive family history is found in 2% of the cases with sagittal suture closure Brain growth pushes the two sides of the patent sutures away from each other, thereby enabling growth of the neurocranium.

This will occur for example when the intracranial pressure drops; the sutures do not experience stretching anymore causing them to fuse.

Diagnosis

The evaluation of a child suspected to have craniosynostosis is preferentially performed in a craniofacial center. The three main elements of analysis include medical history, physical examination and radiographic analysis.

Medical history should in any case include questions about risk factors during pregnancy, the familial rate and the presence of symptoms of elevated intracranial pressure (ICP).

Elevated ICP

  • Symptoms of increased intracranial pressure – such as headache and vomiting – should be questioned after. An elevation of ICP can be present in 4 to 20% of the children where only a single suture is affected. However, even though the children are affected, symptoms are not always present.

Physical examination

Fundoscopy should always be performed in children with craniosynostosis. It is used to find papilledema which is sometimes the only symptom of elevated intracranial pressure shown in these children.

Plain radiography of the skull may be sufficient for diagnosing a single suture craniosynostosis and should therefore be performed, Not only can the sutures be identified more accurately, thus objectively demonstrating a fused suture, but also evaluation of the brain for structural abnormalities and excluding other causes of asymmetric growth are possible at the same time.

Classification

There are several ways to classify craniosynostosis.

  • For example, one can consider the number of closed sutures. If only one of the four sutures is prematurely closed (single suture craniosynostosis), the craniosynostosis is referred to as 'simple' (or 'isolated'). Whereas when two or more sutures are no longer open, the craniosynostosis is 'complex'.

There are a few basic elements involved in surgical intervention which is aimed at normalization of the cranial vault:

  • Surgery for craniosynostosis is often associated with significant perioperative hemorrhage so multiple strategies are often used to minimize blood loss. One such method involves the injection of vasoconstrictive agents (i.e. epinephrine) seven to ten minutes before scalp incision. One potential complication following this procedure involves the gradual movement of the titanium plates towards the brain, induced by resorption of the innermost bone layer of the skull with deposition of new bone on the outermost layer, thereby integrating the titanium plates. One of those is the extended strip craniectomy. This procedure can be performed by using an endoscope, becoming more popular due to the resultant rapid recovery of the child and reduced need for blood transfusion. Most of the bones that collectively form the cranial vault – i.e. the frontal, the parietal and the occipital bones – are removed and reshaped to normalize the contours.

An approach that is currently being evaluated involves the use of springs. This intervention is likely most effective when used in the time frame between three and six months of age.

Metopic synostosis/trigonocephaly

The main elements of metopic suture closure involve a low volume of the anterior cranial fossa, the metopic ridging and hypotelorism. These problems are all addressed during the surgical intervention.

Epidemiology

It is estimated that craniosynostosis affects 1 in 1,800 to 3,000 live births worldwide.