Mutations in genes known to be responsible for most of the recognizable 
syndromes associated with bilateral coronal synostosis can be detected by 
molecular testing. The genetic alterations that could cause unilateral coronal 
synostosis are more elusive. It is recognized that FGFR and TWIST mutations can 
give rise to either bilateral or unilateral coronal synostosis, even in the same 
family. The authors undertook a prospective study of patients presenting with 
synostotic frontal plagiocephaly (unilateral coronal synostosis) to Children's 
Hospital Boston during the period from 1997 to 2000. Mutational analysis was 
performed on all patients and on selected parents whenever familial transmission 
was suspected. Intraoperative anthropometry was used in an effort to 
differentiate those patients in whom a mutation was detected from those in whom 
it was not. The anthropometric measures included bilateral sagittal 
orbital-globe distance, inter medial canthal distance, and nasal angulation. 
Macrocephaly and palpebral angulation were also considered possible 
determinants. There was a 2:1 female preponderance in 47 patients with 
synostotic frontal plagiocephaly. Mutations were found in eight of 47 patients: 
two patients with different single-amino-acid changes in FGFR2, three patients 
with FGFR3 Pro250Arg, and three patients with TWIST mutations. Another patient 
had craniofrontonasal syndrome for which a causative locus has been mapped to 
chromosome X, although molecular testing is not yet available. Two features were 
strongly associated with a detectable mutation in patients with synostotic 
frontal plagiocephaly: asymmetrical brachycephaly (retrusion of both 
supraorbital rims) and orbital hypertelorism. Other abnormalities in the 
craniofacial region and extremities were clues to a particular mutation in 
FGFR2, FGFR3, TWIST, or the X-linked mutation. Neither macrocephaly nor degree 
of nasal angulation nor relative vertical position of the lateral canthi 
correlated with mutational detection. An additional four patients in this study 
had either unilateral or bilateral coronal synostosis in an immediate relative 
and had anthropometric findings that predicted a mutation, and yet no genetic 
alteration was found. This suggests either that the authors' screening methods 
were not sufficiently sensitive or that perhaps there are other unknown 
pathogenic loci. Nevertheless, molecular testing is recommended for infants who 
have unilateral coronal synostosis, particularly if there are the anthropometric 
findings highlighted in this study or an otherwise suspicious feature in the 
child or a parent. Infants with either an identified or a suspected mutation 
usually need bilateral asymmetric advancement of the bandeau and may be more 
likely to require frontal revision in childhood.