Genetic basis of single-suture synostoses: genes, chromosomes and clinical implications

Childs Nerv Syst. 2012 Sep;28(9):1301-10. doi: 10.1007/s00381-012-1781-1. Epub 2012 Aug 8.


Background: Non syndromic craniosynostoses are the most frequent craniofacial malformations worldwide. They represent a wide and heterogeneous group of entities, in which the dysmorphism may occur in a single (simple forms) or in multiple sutures (complex forms). Simple forms present a higher birth prevalence and are classified according to the involved suture and to the corresponding abnormal cranial shape: scaphocephaly (SC; sagittal suture), trigonocephaly (TC; metopic suture), anterior plagiocephaly (unilateral coronal suture), posterior plagiocephaly (unilateral lambdoid suture). They occur commonly as sporadic forms, although a familiar recurrence is sometimes observed, suggesting a mendelian inheritance. The genetic causes of simple craniosynostosis are still largely unknown, as mutations in common craniosynostosis-associated genes and structural chromosomal aberrations have been rarely found in these cases.

Aims: This review is intended to dissect comprehensively the state-of-the art on the genetic etiology of single suture craniosynostoses, in the attempt to categorize all known disease-associated genes and chromosomal aberrations. Possible genotype/phenotype correlations are discussed as useful clues towards the definition of optimized clinical management flowcharts.

Publication types

  • Review

MeSH terms

  • Chromosome Aberrations*
  • Chromosome Disorders / genetics*
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Cranial Sutures / pathology*
  • Craniosynostoses / complications
  • Craniosynostoses / genetics*
  • Craniosynostoses / surgery
  • Cytogenetics
  • Humans
  • Models, Genetic
  • Mutation / genetics
  • Nuclear Proteins / genetics
  • Receptors, Fibroblast Growth Factor / genetics
  • Twist-Related Protein 1 / genetics


  • Core Binding Factor Alpha 1 Subunit
  • Nuclear Proteins
  • RUNX2 protein, human
  • Receptors, Fibroblast Growth Factor
  • TWIST1 protein, human
  • Twist-Related Protein 1