Genotype-phenotype correlations in Axenfeld-Rieger malformation and glaucoma patients with FOXC1 and PITX2 mutations.
OBJECTIVE
To improve the understanding of Axenfeld-Rieger Malformation (ARM)-associated glaucoma and to determine the best glaucoma treatment for patients with ARM who have known genetic defects in FOXC1 or PITX2.


METHODS
Clinical data were collected from patients with diagnosed ARM, in whom we had previously identified disease-causing mutations in either the FOXC1 or PITX2 genes, by examination of patient records and use of clinical questionnaires. One hundred twenty-six patients with ARM, representing 20 different probands, with FOXC1 and PITX2 alterations were included in the study.


RESULTS
ARM-associated glaucoma is a bilateral anterior segment dysgenesis disease that affects males and females equally. Seventy-five percent of the patients with ARM who participated in this study had glaucoma that had developed in adolescence or early adulthood. Of note, the patients with nonocular findings were more likely to have PITX2 defects than FOXC1 defects. Glaucoma in only 18% of patients with either PITX2 or FOXC1 genetic defects responded to medical or surgical treatment (used solely or in combination).


CONCLUSIONS
Patients with FOXC1 mutations have the mildest prognosis for glaucoma development, whereas patients with PITX2 defects and patients with FOXC1 duplication have a more severe prognosis for glaucoma development than do patients with FOXC1 mutations. In the present study, current medical therapies do not successfully lower intraocular pressure or prevent progression of glaucoma in patients with ARM who have FOXC1 or PITX2 alterations. This clinical study also provides useful diagnostic criteria to identify the gene responsible for ARM.
Strungaru
M Hermina
MH
Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada.
Dinu
Irina
I
Walter
Michael A
MA
D000869:Anterior Eye Segment / Q000002:abnormalities*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D005124:Eye Abnormalities / Q000235:genetics*; D005260:Female; D018463:Filtering Surgery; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005838:Genotype; D005901:Glaucoma / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007429:Intraocular Pressure; D007498:Iris / Q000002:abnormalities*; D008297:Male; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012189:Retrospective Studies; D014157:Transcription Factors / Q000235:genetics*; D000097577:Homeobox Protein PITX2
D000959:Antihypertensive Agents; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D014157:Transcription Factors; D000097577:Homeobox Protein PITX2; C112743:FOXC1 protein, human