[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.
Preising
Markus N
MN
Abteilung für Kinderophthalmologie, Strabismologie und Ophthalmogenetik, Klinikum der Universität Regensburg.
Schindler
Sabine
S
Friedrich
Monika
M
Wagener
Heinrich
H
Golan
Ilan
I
Lorenz
Birgit
B
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