Pediatrics

Craniosynostosis

OVERVIEW: What every practitioner needs to know

Are you sure your patient has craniosynostosis? What are the typical findings for this disease?

Most common symptoms and findings include the following:

Cranial and facial deformity

There are several types of craniosynostosis including the following:

Plagiocephaly: Anterior plagiocephaly occurs as a result of premature fusion of a unilateral coronal suture. It is characterized by flattening of the forehead and elevation of the eyebrow on the affected side. The contralateral forehead overgrows as a result of the premature fusion and becomes excessively prominent. The ear on the affected side displaces anteriorly. The deformity can extend into the face causing the chin and nose to deviate to the contralateral side.

Scaphocephaly: Scaphocephaly occurs as a result of premature fusion of the sagittal cranial suture. Compensatory growth causes the skull to elongate, taking the shape of the keel of a boat. The width of the skull is narrow because of the fusion. This is the most common type of craniosynostosis, occurring in 1/2000-4000 births with a male to female predominance of 3:1.

Trigonocephaly: Trigonocephaly occurs as a result of premature fusion of the metopic suture, which extends from the nose to the sagittal suture, dividing the forehead in half. Trigonocephaly accounts for 10% of craniosynostosis and has a male to female ratio of 3:1. The deformity is characterized by a prominent ridge in the central part of the forehead and hyportelorism (narrowly spaced orbits). The anterior portion of the skull assumes a triangular shape.

Kleeblattschädel: Kleeblattschädel deformity occurs when multiple cranial sutures fuse prematurely. The condition is characterized by a trilobed cloverleaf skull. The deformity is rare, occurring in less than 1/1,000,000. Fewer than 150 cases have been reported. Affected patients frequently have hydrocephalus and mental retardation.

Acrocephaly: Acrocephaly occurs with combined premature fusion of the lambdoid, coronal, and sagittal sutures and can be seen in Crouzon and Apert syndromes. The anterior skull overgrows, causing the cranium to slope from front to back.

Increased intracranial pressure: This is usually low grade or subtle and more commonly occurs with premature fusion of more than one suture. Headache is the most common symptom of increased intracranial pressure. The most common physical findings of intracranial pressure are papilledema and bulging of the fontanelle. When severe and of long standing, "thumbprinting" and thinning of the cranium can be seen.

Neurobehavioral abnormalities: The majority of studies have demonstrated a mild to moderate risk of neurobehavioral problems in infants and children with single-suture craniosynostosis. The relationship between the structural abnormalities of the skull and brain and development are unclear and it is not known whether craniosynostosis causes or correlates with neurobehavioral problems. There is no definitive proof that surgical correction of craniosynostosis prevents future developmental delays.

Physical Examination: The diagnosis of craniosynostosis is typically based on physical examination. Computed tomography (CT) confirms the diagnosis and helps identify the fused suture, the extent of the bony deformity, the shape of the skull base, and any structural abnormalities of the brain.

What other disease/condition shares some of these symptoms?

Syndromes such as Crouzon, Apert, Pfeiffer and others all have craniosynostosis as a component of the constellation of findings.

What caused this disease to develop at this time?

Genetics:Autosomal dominant inheritance has been identified in syndromic forms of craniosynostosis, although some patients have spontaneous mutations. Familial cases make up 25%-45% of the total number of cases and is variable for the different syndromes. No inheritance pattern has been identified for nonsyndromic forms of craniosynostosis. Polymerase chain reaction (PCR) analysis and DNA sequencing of the FGFR2 gene and the entire TWIST gene, and point mutation testing of the FGFR1 and FGFR3 genes can be performed.

Crouzon, Apert, and Pfeiffer syndromes have mutations in the group of genes coding for fibroblast growth factor receptor (FGFR).

Positional plagiocephaly: Positional or deformational plagiocephaly is a disorder that occurs when either the back or side of the skull flattens secondary to the head being in one position for too long. Since the start of the "Back to Sleep" campaign, the incidence of positional plagiocephaly has risen. Congenital torticollis can also place prolonged pressure on one side of the skull, causing an anterior type of cranial and facial flattening.

Would imaging studies be helpful? If so, which ones?

CT confirms the diagnosis and helps identify the fused suture, the extent of the bony deformity, the shape of the skull base, and any structural abnormalities of the brain.

Confirming the diagnosis

If there is posterior skull flattening only (positional plagiocephaly) and the child is developmentally normal, refer the patient to a craniofacial team. The diagnosis can frequently be made clinically, obviating the need for radiographs or CT.

If there is a high risk of craniosynostosis, based on abnormalities of the skull or face and/or concomitant findings suggestive of a syndromic diagnosis, referral to a craniofacial team should be made before imaging. Most craniofacial teams have specific CT protocols to evaluate children with suspected craniosynostosis. A head and face CT with three-dimensional imaging will aid in the diagnosis and help plan surgery. Three-dimensional CT results in a 3-10 times increase in radiation exposure over conventional CT of the head but permits better surgical planning.

If you are able to confirm that the patient has craniosynostosis, what treatment should be initiated?

All infants and children with an abnormal head shape should be referred early to a craniofacial team for further evaluation. An experienced team can frequently make the diagnosis of positional plagiocephaly without the need for radiography or CT. Children with positional plagiocephaly can usually be treated with head repositioning alone. For children with severe positional plagiocephaly, an orthotic helmet may be indicated to help reshape the skull.

Treatment for children with confirmed craniosynostosis is complex and requires an experienced multidisciplinary team of neurosurgeons, craniofacial surgeons, anesthesiologists, intensivists, geneticists, dentists, orthodontists, and pediatricians. Surgery is performed early to release growth-arrested sutures and reconstruct the skull to help normalize the shape of the face and skull and prevent increased intracranial pressure.

What are the adverse effects associated with each treatment option?

The adverse effects associated with surgical correction of craniosynostosis include cerebrospinal fluid leak, injury to the brain, wound healing problems, cranial asymmetry, and the need for further surgery.

What are the possible outcomes of craniosynostosis?

The prognosis for surgical correction of nonsyndromic cranisynostosis is good. Most cases of nonsyndromic craniosynostosis can be corrected with one surgical procedure. Syndromic craniosynostosis often requires several surgical procedure to correct both the cranial and facial deformities.

What causes this disease and how frequent is it?

Craniosynostosis: The overall incidence is 1/2000 births

Scaphocephaly accounts for 50% of all cases of craniosynostosis. The incidence is 1/2000-4000 live births.

Trigonocephaly accounts for 10% of all cases of craniosynostosis with a 3:1 male to female predominance. The incidence is 1/2500-15,000 live births.

Positional plagiocephaly can affect up to 15% of children.

Plagiocephaly occurs in 1/10,000 live births.

Crouzon and Apert syndromes are the most common forms of syndromic craniosynostosis.

Apert syndrome occurs in 1/160,000-200,000 live births. It accounts for approximately 4.5% of all cases of craniosynostosis.

Crouzon syndrome occurs in 1/25,000 live births.

Autosomal dominant inheritance has been identified in syndromic forms of craniosynostosis, although some patients have spontaneous mutations. Familial cases make up 25%-45% of the total number of cases and is variable for the different syndromes. No inheritance pattern has been identified for nonsyndromic forms of craniosynostosis. PCR analysis and DNA sequencing for the FGFR2 gene and the entire TWIST gene, and point mutation testing of the FGFR1 and FGFR3 genes can be performed.

Crouzon, Apert, and Pfeiffer syndromes have mutations in the group of genes coding for fibroblast growth factor receptor (FGFR).

How do these pathogens/genes/exposures cause the disease?

Mutations in the genes encoding fibroblast growth factor receptors 1, 2 and 3 (FGFR-1, FGFR-2, FGFR-3), TWIST and MSX2 (muscle segment homebox 2) have been identified in certain syndromic craniosynostoses.

How can craniosynostosis be prevented?

There are no methods of preventing craniosynostosis.

What is the evidence?

The majority of studies have demonstrated a mild to moderate risk of neurobehavioral problems in infants and children with single-suture craniosynostosis. The relationship between the structural abnormalities of the skull and brain and development are unclear and it is not know whether cranisynostosis causes or correlates with neurobehavioral problems. There is no definitive proof that surgical correction of craniosynostosis prevents future developmental delays.

Star, JR, Kapp-Simon, KA, Cloonan, YK. "Presurgical and postsurgical assessment of the neurodevelopment of infants with single-suture craniosynostosis: comparison with controls". J Neurosurg. vol. 1072. 2001. pp. 103-10.

(Because of a tendancy for patients with single-suture craniosynostosis to perform in the delayed range on neurodevelopmental examinations, the authors' findings support recommendations for neurodevelopmental screening in infants with single-suture craniosynostosis.)

Kapp-Simon, KA, Speltz, ML, Cunningham, ML. "Neurodevelopment of children with single-suture craniosynostosis: a review". Child Nerv Syst. vol. 23. 2007. pp. 269-81.

(Available literature on neurocognitive development in children with single-suture craniosynostosis is suggestive of mild but persistent neuropsychological deficits that become more significant as cognitive demands increase at school age.)

Chieffo, D, Tamburrini, G, Massimi, L. "Long-term neuropsychological development in single-suture craniosynostosis treated early". J Neurosurg Pediatr. vol. 5. 2010. pp. 232-7.

(The study supports the hypothesis that children with sagittal or unicoronal craniosynostosis may still manifest lower than average results at long-term selective neuropsychological evaluations despite early surgical treatment.)

Ongoing controversies regarding etiology, diagnosis, treatment

Most of the controversy involves the effect treatment has on the long-term outcome of neurobehavioral abnormalities.

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