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At a glance

A congenital skull anomaly characterized by premature fusion of one or more cranial sutures.

Synonym

Craniostenosis.

Incidence

It is estimated to be approximately 1:2,000-2,500 live births. Approximately 75 to 80% of all craniosynostosis (CS) cases are nonsyndromic (isolated CS), while in the remaining 20 to 25% CS is part of an underlying syndrome (syndromic CS). Sagittal CS is the most common type and accounts for 40 to 55% of all nonsyndromic CS cases and is about four times more common in males than in females. The second most common type is coronal CS accounting for approximately 20 to 25% of nonsyndromic CS and is more frequent in females (about 60-75% of all cases) and can either be uni- or bilateral. Metopic CS accounts for about 5 to 15% of nonsyndromic CS and is approximately three times more frequent in males. Finally, lambdoid CS is responsible for up to 5% of all nonsyndromic CS. Complex CS refers to the 5 to 11% of nonsyndromic CS cases with two or more sutures affected. Typically, these patients have a more severe clinical course with about two-thirds of them suffering from increased intracranial pressure (ICP), often associated with chronic headache and mental delay, and in up to three-quarters an Arnold-Chiari Malformation Type I is present.

Genetic inheritance

A positive family history is present in up to 40% of cases, with genetic syndromes accounting for at least 50% of those cases. Both autosomal dominant and autosomal recessive inheritance have been described, but the majority of nonsyndromic CS cases are sporadic. Currently, there are about 60 different genes known whose mutations can be associated with CS as a major feature, among them are fibroblast growth factor receptors genes FGFR1 (☞Acrocephalosyndactyly Type V; Pfeiffer Syndrome), FGFR2 (☞Acrocephalosyndactyly Type I; Apert Syndrome, and ☞Acrocephalosyndactyly Type II; Crouzon Syndrome), FGFR3 (Muenke Syndrome), the TWIST1 gene (☞Acrocephalosyndactyly Type III; Saethre-Chotzen Syndrome), EFNB1 (☞Craniofrontonasal Dysplasia), and MSX2 gene (Boston craniosynostosis). Complex CS and extracranial complications are more likely to be associated with a genetic background for the CS.

Pathophysiology

The exact etiology, factors, and molecular mechanisms leading to nonsyndromic CS are still not fully understood, but environmental and genetic factors seem to play a role. The developing brain is the driving power behind skull growth and the abnormal cranial suture development in CS results in growth failure perpendicular to the affected suture and compensatory overgrowth of the skull parallel (along) to the affected suture. Environmental factors etiologically linked to CS include rickets and hyperthyroidism. Drugs (or toxins) that may be involved in CS include phenytoin, retinoids, valproic acid, aminopterin/methotrexate, fluconazole, cyclophosphamide, and maternal smoking. In some cases, local intrauterine factors related to constraint of the fetus (eg, abnormal positioning in utero, multiple pregnancy, oligohydramnios) have been linked to CS.

Diagnosis

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