Excerpt from Craniosynostosis

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Background

Craniosynostosis is the premature fusion of the cranial sutures. Craniosynostosis can occur as an isolated defect or as part of a syndrome and is recognized in 2 forms: simple and compound. In simple craniosynostosis, only 1 cranial suture is involved; compound craniosynostosis involves 2 or more sutures.

Pathophysiology

In the recent literature, mutations have been reported in gene coding for fibroblast growth factor receptors (FGFRs) in affected families with craniosynostosis. The receptors mediate the effects of the fibroblast growth factors that modulate cellular processes, such as growth, differentiation, migration, and survival. Mutations of the FGFR2 gene, located on chromosome 7, have been recognized in Crouzon disease and in Apert, Jackson-Weiss, and Pfeiffer syndromes. Some cases of Pfeiffer syndrome and Crouzon disease involve mutations of both the FGFR1 and FGFR3 genes. These mutations account for a small fraction of cases of craniosynostosis; most cases have an unclear etiology.¹

With the use of immunocytochemistry techniques, abnormal osteoblastic activity has been observed within the synostotic bone, along with decreased growth rate and alkaline phosphatase production. Histopathologic examinations of resected sutures have demonstrated new bone formation at various stages. These stages range from trabecular interdigitation across the fibrous tissue to complete bony fusion.

Frequency

United States

The estimated incidence of simple or compound craniosynostosis is approximately 1 case per 2000 live births. Approximately 80-90% of cases involve isolated defects, while the remaining cases are part of a recognized syndrome. In the isolated cases, the sagittal suture is affected most often, followed by the coronal, lambdoid, and metopic sutures.

Mortality/Morbidity

In most patients with craniosynostosis involving a single suture, the primary concern is cosmetic. Early diagnosis and surgical therapy are essential to prevent lifelong craniofacial deformity. Patients with diffuse craniosynostosis are at risk of developing increased intracranial pressure (ICP). Patients can have airway problems because of a hypoplastic maxilla or ophthalmologic problems related to shallow orbits. Patients with Apert, Pfeiffer, or Carpenter syndromes also have significant surgical issues related to fusion anomalies of the digits.

Race

No racial predilection exists.

Sex

Several forms of craniosynostosis have sex predilections. A slight male predominance is observed in cases of sagittal synostosis, and a female predominance is noted in cases of coronal synostosis.

Age

Most cases are evident during the neonatal period.

Anatomy

The bones of the cranium (frontal, parietal, temporal, and occipital) are well developed by the fifth month of gestation. The membranous skull bones are joined by connective tissue at the sagittal, coronal, metopic, lambdoid, and squamous sutures. The anterior fontanelle is at the junction of the frontal and parietal bones, and it represents the intersection of the metopic, coronal, and sagittal sutures. It normally closes in children by the age of 20 months. The posterior fontanelle, located at the junction of the lambdoid and sagittal sutures, closes by the age of 3 months. Mature suture closure occurs by the age of 12 years, but completion of fusion continues into the third decade of life and beyond.

Clinical Details

Skull growth is restricted in the plane perpendicular to the prematurely fused suture and enhanced in the plane parallel to it. Synostosis of the sagittal suture produces a long and narrow skull, called scaphocephaly or dolichocephaly. The anteroposterior diameter of the skull is increased, whereas the transverse diameter is decreased. Sagittal synostosis is most commonly seen in men. Although the biparietal diameter is low, the actual head volume is normal; therefore, no increase in ICP, no hydrocephalus, and no neurologic deficits are usually present.

Synostosis of the coronal suture can occur bilaterally (brachycephaly) or unilaterally (plagiocephaly). Brachycephaly results in a short, wide skull, with a shortened anteroposterior diameter and a flattened occiput and forehead. Brachycephaly is seen more commonly in females and is associated with a higher incidence of neurologic complications, including increased ICP, optic atrophy, and mental retardation, than sagittal synostosis, which is usually associated with normal intellectual function. A higher incidence of anomalies is also associated with coronal craniosynostosis: in plagiocephaly, the incidence rate is 33%; in brachycephaly, the incidence can be as high as 59%.

Synostosis of the lambdoid sutures is less common than sagittal and coronal synostosis. A marked flattening and underdevelopment of the posterior fossa are present with lambdoid synostosis, and overgrowth of the bregma may occur, resulting in a tall cranial shape called oxycephalic or turricephalic skull.

Synostosis of the metopic suture, which occurs in utero, is rare. Called trigonocephaly, it results in a pointed forehead and hypotelorism, with an increased risk for associated anomalies of the forebrain. Other anomalies often encountered with metopic synostosis include cleft palate, coloboma, and a wide array of urinary tract abnormalities.

A combined synostosis of the coronal and sagittal sutures results in a severe form of craniosynostosis termed oxycephaly, which can lead to microcephaly. In addition, increased ICP is associated with significant neurologic complications.

The most severe form of craniosynostosis is called the kleeblattschädel deformity, or cloverleaf skull, in which the coronal, sagittal, and lambdoid sutures are all affected. The skull resembles a cloverleaf shape, and patients typically have a bulging forehead, proptotic eyes, and severe neurologic impairment.

The most common syndrome-associated synostoses are Crouzon disease and Chotzen and Apert syndromes, which account for more than two thirds of syndrome-related craniosynostosis.

• Asymmetric craniosynostosis and plagiocephaly characterize Chotzen syndrome, which is inherited as an autosomal dominant trait and is associated with facial asymmetry, ptosis of the eyelids, shortened fingers, a low frontal hairline, a long pointed nose, and soft-tissue syndactyly. Cervical fusion is often seen at the level of the C2-3 vertebrae.


• Crouzon disease is inherited as an autosomal dominant trait in 75% of patients. The remaining 25% of cases are sporadic. The skull shape varies depending on the order of fusion, but brachycephaly is the most common result due to closure of the coronal and basal skull sutures. Associated findings include ocular proptosis, maxillary hypoplasia, parrot-beak nose, and ocular hypertelorism with normal limbs. Hydrocephalus is more common in Crouzon disease than in the other syndromes, and chronic tonsillar herniation is a common MRI finding in patients with Crouzon disease.


• Apert syndrome (acrocephalosyndactyly) is an autosomal dominant disorder characterized by coronal synostosis in conjunction with a malformed and short cranial base. It is associated with extensive syndactyly of the second, third, and fourth fingers (mitten hands); broad thumbs with radial deviation; toe syndactyly (sock toes); and visual impairment. Patients with Apert syndrome have an increased risk of mental retardation; 50% of patients have an intelligence quotient lower than 70. Cervical vertebrae fusion, primarily at the C5-6 vertebrae, occurs in 68% of patients.


• Carpenter syndrome is inherited as a rare autosomal recessive trait and usually results in the kleeblattschädel deformity. Soft-tissue syndactyly is always present in the hands and feet. Mental retardation is common.


• Pfeiffer syndrome is autosomal dominant and differs from Apert syndrome by the presence of polydactyly. Pfeiffer syndrome is categorized into 3 types, with varying deformities.
  
  
  • Type I is the most common form and often results in moderate-to-severe hearing loss. Abnormalities found on CT scans include auditory canal stenosis or atresia and either hypoplasia or enlargement of the middle ear cavity. Type I is associated with broad thumbs and toes with variable syndactyly. The eyes often are spaced widely apart and prominent.
  
  
  • Type II is characterized by a cloverleaf skull, severe proptosis, and ankylosis of the elbows.
  
  
  • In addition to manifesting bilateral craniosynostosis and ocular proptosis, patients with type III Pfeiffer syndrome may present with developmental delays, hydrocephalus, hearing defects, and short stature. Fusion of the cervical spine, a cone-shaped epiphysis, and hypoplastic bones about the elbow are additional features.


• Jackson-Weiss syndrome has been mapped to the same gene as Crouzon disease. Both coronal and basal skull synostoses are present. Associated findings include enlarged great toes and craniofacial abnormalities similar to those found in Pfeiffer syndrome but without thumb abnormalities.


• Each syndrome has an increased risk of elevated ICP, hydrocephalus, optic atrophy, respiratory problems due to a deviated septum, and disorders of speech and hearing. Surgical intervention results in an improved cosmetic appearance along with a substantially decreased risk of neurologic complications.

Increased ICP is frequently caused by abnormalities of cerebral venous drainage as a result of maldevelopment of the foramina at the skull base.

Preferred Examination

Patients in whom craniosynostosis is suggested should undergo a careful clinical examination, with the clinician looking for abnormalities of the skull and extremities.

Plain radiography is the first radiologic step. Plain radiography quickly and simply identifies skull-shape abnormalities, which are seen in most patients with craniosynostosis. With this simple and inexpensive examination, usually all cranial sutures can be surveyed for patency. Conventional cranial CT scans with bone windows or 3-dimensional (3D) CT scans are frequently obtained to confirm bony abnormalities and to delineate any associated intracranial anomalies. Three-dimensional CT is the criterion standard for the evaluation of craniosynostosis.

Limitations of Techniques

The entire length of each suture is not always visible on plain radiographs, and some patients have only a small bony bar limiting growth at a particular suture. If the skull shape is entirely normal, craniosynostosis is unlikely.

CT is considered expensive and may require that the patient be sedated.

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