PURPOSE: Craniosynostoses are premature ossifications of cranial sutures. They 
occur isolated and syndromic. Syndromic craniosynostoses are mainly associated 
with mutations of the Fibroblast Growth Factor Receptors (FGFR) 1 - 3. This 
paper gives an overview of the etiology and pathophysiology of isolated and 
syndromic craniosynostoses and discusses the molecular genetic results in 21 
index cases (19 seemingly isolated craniosynostoses, 2 cases with a clinical 
diagnosis of Crouzon's syndrome).
METHOD: Mutation analysis in exons of the FGFR 1 - 3 known to be preferentially 
affected in craniosynostoses was performed on DNA samples from peripheral blood 
and bone specimen excised at the time of surgery to correct the 
craniosynostosis.
RESULTS: In a girl with seemingly isolated plagiocephaly we identified a P250L 
(749C-->T) mutation in FGFR3. Her mother showed minor signs of craniosynostosis 
when the family was re-evaluated. She was shown to carry the same mutation. In 
two patients with suspected Crouzon's syndrome 2 different mutations were 
detected at the same nucleotide (1025G-->A or C) and confirmed the clinical 
diagnosis. No mutation was found in 18/19 seemingly isolated craniosynostosis 
cases.
CONCLUSION: In contrast to syndromic forms isolated craniosynostoses are rarely 
associated with mutations in FGFR. The affection of further family members is a 
strong indication of involvement of FGFR mutations. Because of variable 
expressivity, parents should be examined carefully in isolated craniosynostoses 
to identify minor signs.