May 2006
Volume 47, Issue 13
ARVO Annual Meeting Abstract  |   May 2006
Genotype–Phenotype Correlation in Axenfeld–Rieger Malformation (ARM) and Glaucoma Patients With FOXC1 and PITX2 Mutations
Author Affiliations & Notes
  • M.H. Strungaru
    Medical Genetics, University, Edmonton, AB, Canada
  • M.A. Walter
    Medical Genetics and Ophthalmology, University of Alberta, Edmonton, AB, Canada
  • Footnotes
    Commercial Relationships  M.H. Strungaru, None; M.A. Walter, None.
  • Footnotes
    Support  CIHR
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 181. doi:
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      M.H. Strungaru, M.A. Walter; Genotype–Phenotype Correlation in Axenfeld–Rieger Malformation (ARM) and Glaucoma Patients With FOXC1 and PITX2 Mutations . Invest. Ophthalmol. Vis. Sci. 2006;47(13):181.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : More than 40% of patients with ARM have mutations of two transcription factors, either the Forkhead box gene (FOXC1) or the Pituitary homeobox (PITX2) gene. We conducted a clinical study to improve the understanding of the ARM–associated glaucoma, and to determine the best glaucoma treatment for ARM patients with known genetic defects in FOXC1 or PITX2.

Methods: : Clinical data was collected from patients diagnosed with ARM in whom we had previously identified disease–causing mutations in either the FOXC1 or PITX2 genes. Through the examination of patient records and use of clinical questionnaires, we obtained information regarding: the incidence of glaucoma among these ARM patients, the age of diagnosis with ARM and of glaucoma, the distribution of ARM/glaucoma in females and males, the distribution of ARM/glaucoma among different ethnicities, which ocular/ non–ocular malformations were present, if the ARM–associated glaucoma was an unilateral or bilateral disease, what glaucoma treatment(s) was used, and if the treatment was successful in managing the ARM–associated glaucoma.

Results: : Our laboratory has identified FOXC1 and PITX2 alterations in 20 different probands, representing a total of 112 patients with ARM. From these patients, 81 were found to have FOXC1 defects (13 different probands) while 31 have PITX2 defects (7 different probands). From the 81 patients with FOXC1 defects, 51 had FOXC1 gene duplications and 30 had FOXC1 mutations. From 31 patients with PITX2 defects, 22 had mutations while 9 had PITX2 gene deletions. From 112 patients, we have collected complete clincal data from 42 patients, incomplete clincal data (to date) from 38 patients, and 32 patients were lost to followup or didn’t wish to participate in our study. Results were tabulated and compared using statistical analyses.

Conclusions: : Preliminary analyses are consistent with the hypothesis that ARM–associated glaucoma is a bilateral disease, equally prevalent in males and females. Interestingly, patients with non–ocular findings appear likely to have PITX2 rather than FOXC1 mutations. Importantly, the glaucoma in the majority of patients (45/55) with either PITX2 or FOXC1 genetic defects appears to have failed to respond to medical or surgical (used solely or in combination) treatment. We anticipate that comparison of our previous molecular studies of the consequences of FOXC1 and PITX2 mutations with these clincal disease parameters will allow the creation of an evidence–based treatment strategy for ARM–associated glaucoma.

Keywords: clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials • genetics • mutations 

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