Head and Brain Malformations

The most relevant head malformation is a condition called craniosynostosis, or the premature fusion of one or more of the head's sutures. The human head is composed of multiple bones held together by several sutures, namely the metopic, coronal, sagittal, and lambdoid sutures. Simple craniosynostosis is when only one suture is involved, while compound craniosynostosis involves two or more sutures. The most common suture affected is the sagittal suture (50 percent of cases), followed by the coronal suture (25 percent), and metopic suture (10 percent). Lambdoid synostosis is very rare, with an incidence of 3 per 100,000 births. The overall prevalence of craniosynostosis is approximately 1 per 2,000 births, or 0.05 percent of children. One-fifth of craniosynostosis cases occur as one of more than 150 different syndromes, while the remainder occur as an isolated, nonsyndromic condition.

The etiology of craniosynostosis is unknown. Several risk factors for the development of this condition have been identified and can be categorized by maternal factors, paternal factors, and infant factors. Maternal factors include white race, advanced age, smoking habits, residence at high altitude, and use of certain medications. Paternal factors include specific occupations, such as in agriculture, forestry, or mechanics. Infant factors include male sex. Genetics also play a role, given that a certain percentage of cases are familial and autosomal dominant in inheritance.

One known genetic mutation is in the gene encoding fibroblast growth factor receptor (FGFR), which is known to be expressed in the cranial sutures. Therefore, if a receptor is produced with a faulty molecular structure or in insufficient quantities, the skull's sutures may not fuse correctly.

Craniosynostosis is diagnosed by physical examination, X-rays, and computed tomography (CT). Physical examination findings may include a misshapen head as well as nonpatent suture lines and fontanelles (soft spots) on the child's head. The signs of craniosynostosis on X-ray include bony bridging across the suture that produces beaking or heaping up of bone; sutures that appear very straight and narrow; and loss of suture clarity. Because CT offers a clearer picture than X-rays, it is the most reliable diagnostic tool.

Craniosynostosis that goes uncorrected may result in increased intracranial pressure (ICP), an asymmetric face, malocclusion (misaligned teeth), and strabismus. Correction, therefore, is surgical and is preferably performed between 3 and 9 months of age by a pediatric neurosurgeon. The different surgical options include strip craniectomy and cranial vault remodeling. Strip craniectomy can now be performed with a minimally invasive, endoscopic technique.

By definition, syndromic craniosynostosis involves multiple organ systems, that is, cardiac, renal, and musculoskeletal. The two most common syndromes are Crouzon's disease and Apert's syndrome, both of which are caused by autosomal dominant mutations on the FGFR2 gene on chromosome 10. The incidence of Crouzon's disease is one per 25,000 and it accounts for 5 percent of craniosynostosis cases. External findings include wide-set and bulging eyes (hypertelorism and proptosis, respectively), beaked nose, and cleft palate. The patient's brain may be affected by hydrocephalus and/or Chiari malformation.

Apert's syndrome affects one per 160,000 and is marked by syndactyly (webbed fingers/toes), hypertelorism, and shallow eye orbits. Intracranial findings in a patient with Apert's syndrome may include megalocephaly and agenesis of the corpus callosum, both of which may contribute to cognitive deficits. Patients may also have cardiac and renal anomalies, such as atrial/ven-tricular septal defect and hydronephrosis, respectively.

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