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

Background: Non sy ndromic craniosy nostoses are the most f requent craniof acial malf ormations worldwide. They represent a wide and heterogeneous group of entities, in which the dy smorphism may occur in a single (simple f orms) or in multiple sutures (complex f orms). Simple f orms present a higher birth prev alence and are classif ied according to the inv olv ed 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 f orms, although a f amiliar recurrence is sometimes observ ed, suggesting a mendelian inheritance. The genetic causes of simple craniosy nostosis are still largely unknown, as mutations in common craniosy nostosis-associated genes and structural chromosomal aberrations hav e been rarely f ound in these cases. Aims: This rev iew is intended to dissect comprehensiv ely the state-of -the art on the genetic etiology of single suture craniosy nostoses, in the attempt to categorize all known disease-associated genes and chromosomal aberrations. Possible genoty pe/phenoty pe correlations are discussed as usef ul clues towards the def inition of optimized clinical management flowcharts.