Ocular abnormalities in Apert syndrome: genotype/phenotype correlations with fibroblast growth factor receptor type 2 mutations.
OBJECTIVE
Apert syndrome, a disorder of craniosynostosis, syndactyly, and other craniofacial malformations, is caused by point mutations (Ser252Trp or Pro253Arg) in the fibroblast growth factor receptor 2 gene. This study's goal was to determine ophthalmic phenotype/genotype correlations in patients with either mutation.


METHODS
A retrospective chart review of demographic and ophthalmologic data was performed for 18 children carrying either the S252W (11) or the P253R (7) mutation. Fisher exact tests were performed to determine significance of variable phenotypes between the two mutation groups.


RESULTS
In the P253R group, 85% had strabismus (14% required surgery), 71% had ptosis, 43% had amblyopia, 14% had nasolacrimal duct obstruction, 14% had myopia, 14% had hyperopia, and 14% had astigmatism. In the S252W group, 91% had strabismus (64% required surgery), 73% had ptosis, 73% had amblyopia, 100% had nasolacrimal duct obstruction, 36% had myopia, 9% had hyperopia, and 82% had astigmatism. Overall, S252W and P253R groups showed significantly different numbers of patients with strabismus requiring surgery (p = 0.039), superior rectus muscle underaction (p = 0.024), nasolacrimal duct obstruction (p = 0.0002), and astigmatism (p = 0.005).


CONCLUSIONS
Compared with patients with the P253R mutation, Apert syndrome patients with the S252W mutation may have more severe ocular phenotypes with a higher likelihood of developing strabismus, especially vertical deviation. They also are more likely to develop astigmatic refractive errors and tearing secondary to nasolacrimal system anomalies.
Jadico
Suzanne K
SK
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Young
David A
DA
Huebner
Alexandra
A
Edmond
Jane C
JC
Pollock
Avrum N
AN
McDonald-McGinn
Donna M
DM
Li
Yi-Ju
YJ
Zackai
Elaine H
EH
Young
Terri L
TL
D000168:Acrocephalosyndactylia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001251:Astigmatism / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005124:Eye Abnormalities / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D012030:Refractive Errors / Q000235:genetics; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013285:Strabismus / Q000235:genetics
D051497:Receptor, Fibroblast Growth Factor, Type 2