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  • Test code: 04723
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Axenfeld-Rieger Panel

Test description

The Invitae Axenfeld-Rieger Panel analyzes two genes, FOXC1 and PITX2, that are associated with Axenfeld-Rieger syndrome (ARS). Genetic testing of these genes may help confirm clinical diagnosis and provide information for recurrence-risk estimation and counseling.

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Primary panel (2 genes)
Add-on Aniridia Gene (1 gene)

Aniridia may be diagnosed as severe iris hypoplasia associated with ARS. The PAX6 gene can be included for testing at no additional charge.

PAX6

  • Axenfeld-Rieger syndrome
    • Axenfeld anomaly
    • iridogoniodysgenesis
    • Peters anomaly
    • Rieger anomaly
    • Rieger syndrome

Axenfeld-Rieger syndrome (ARS) refers to overlapping heterogeneous disorders that are primarily characterized by an ophthalmological abnormality but can also include comorbidities such as dysmorphic facial features, abnormal dentition, and, less commonly, heart defects, hearing loss, and pituitary function-related delayed growth. Abnormal development of the anterior segment of the eye manifests as iris hypoplasia or corectopia and anteriorly displaced Schwalbe’s line with iridocorneal adhesions. Nearly half of affected individuals develop glaucoma. Affected individuals may exhibit different degrees of abnormality in each eye.

Pathogenic changes in FOXC1 and PITX2 account for 15%–40% of ARS cases.

Axenfeld-Rieger syndrome is inherited in an autosomal dominant pattern.

Axenfeld-Rieger syndrome is a completely penetrant disorder.

The prevalence of Axenfeld-Rieger syndrome is estimated at 1 in 200,000 individuals.

  1. Idrees, F, et al. A review of anterior segment dysgeneses. Surv Ophthalmol. 2006; 51(3):213-31. PMID: 16644364
  2. Tümer, Z, Bach-Holm, D. Axenfeld-Rieger syndrome and spectrum of PITX2 and FOXC1 mutations. Eur. J. Hum. Genet. 2009; 17(12):1527-39. PMID: 19513095
  3. Weisschuh, N, et al. Clinical utility gene card for: Axenfeld-Rieger syndrome. Eur. J. Hum. Genet. 2011; 19(3). PMID: 20940740
  4. Dressler, S, et al. Dental and Craniofacial Anomalies Associated with Axenfeld-Rieger Syndrome with PITX2 Mutation. Case Rep Med. 2010; 2010:621984. PMID: 20339518
  5. Alward, WL. Axenfeld-Rieger syndrome in the age of molecular genetics. Am. J. Ophthalmol. 2000; 130(1):107-15. PMID: 11004268
  6. Cella, W, et al. Structural assessment of PITX2, FOXC1, CYP1B1, and GJA1 genes in patients with Axenfeld-Rieger syndrome with developmental glaucoma. Invest. Ophthalmol. Vis. Sci. 2006; 47(5):1803-9. PMID: 16638984
  7. Strungaru, MH, et al. Genotype-phenotype correlations in Axenfeld-Rieger malformation and glaucoma patients with FOXC1 and PITX2 mutations. Invest. Ophthalmol. Vis. Sci. 2007; 48(1):228-37. PMID: 17197537
  8. Weisschuh, N, et al. Novel mutations of FOXC1 and PITX2 in patients with Axenfeld-Rieger malformations. Invest. Ophthalmol. Vis. Sci. 2006; 47(9):3846-52. PMID: 16936096
  9. Reis, LM, et al. PITX2 and FOXC1 spectrum of mutations in ocular syndromes. Eur. J. Hum. Genet. 2012; 20(12):1224-33. PMID: 22569110
  10. Orphanet. Axenfeld-Rieger syndrome. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=782 Accessed February 2016.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
FOXC1 NM_001453.2
PAX6 NM_000280.4
PITX2 NM_153427.2