Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Craniosynostoses - Overview [Q75.0]

Dr. med. Imma Rost, Dipl.-Biol. Christina Sofeso

Scientific Background

Craniosynostosis is the term for premature fusion of cranial sutures. Depending on which cranial sutures are affected, it causes abnormal growth of the skull and sometimes a typical head shape. Most forms of primary craniosynostosis are congenital and may occur as isolated cases or represent one sign of a number of complex syndromes. The frequency is 1 in 2,000–3,000. With a proportion of approx. 50%, sagittal synostosis is the most common form among the isolated cases. The complex forms are characterized by one or several synostoses and, in some cases, other signs and symptoms of a pathologic development of bone structures, such as syndactyly. The classic craniosynostosis syndromes include:

These syndromes follow an autosomal dominant pattern of inheritance. All except the Saethre-Chotzen syndrome are caused by mutations in the genes of the fibroblast growth factor receptors (FGFR) 1, 2 and 3. The Saethre-Chotzen syndrome is usually caused by mutations in the TWIST1 gene. The syndromes overlap clinically.

Mutations in the TWIST1 gene were detected in a small number of patients suffering from isolated single suture synostoses, especially sagittal and coronary synostoses.

The molecular cause of the premature fusion has not yet been fully understood. The fibroblast growth factor receptors that are involved are tyrosine kinase receptors which play an important role in the ossification. TWIST interacts with FGFR.

Complications include increase of the intracranial pressure, visual impairment, hearing disorders and, in some of the syndromes, developmental delay. The main treatment is surgery.