[On the effect of mutations of the fibroblast growth factor receptors as exemplified by three cases of craniosynostoses].
OBJECTIVE
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).


METHODS
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.


CONCLUSIONS
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.
Abteilung für Kinderophthalmologie, Strabismologie und Ophthalmogenetik, Klinikum der Universität Regensburg.
Markus N
MN
Preising
Sabine
S
Schindler
Monika
M
Friedrich
Heinrich
H
Wagener
Ilan
I
Golan
Birgit
B
Lorenz
D000328:Adult; D002648:Child; D003394:Craniofacial Dysostosis / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D003398:Craniosynostoses / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D003399:Craniotomy; D004252:DNA Mutational Analysis; D005128:Eye Diseases / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006580:Genetic Carrier Screening; D006801:Humans; D007223:Infant; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000235:genetics*
D017468:Receptors, Fibroblast Growth Factor; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3