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  • Test code: 05133
  • 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 Early-Onset Glaucoma Panel

Test description

The Invitae Early-Onset Glaucoma Panel analyzes three genes that are associated with early-onset glaucoma. Genetic testing of these genes may help confirm a clinical diagnosis and provide information for recurrence-risk estimation and genetic counseling.

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Primary panel (3 genes)

CYP1B1 FOXC1 PITX2

  • Axenfeld-Rieger syndrome
  • glaucoma
    • juvenile open-angle glaucoma
    • primary congenital glaucoma
    • primary open-angle glaucoma
  • Peters anomaly

Primary congenital glaucoma (PCG) is an early-onset form of glaucoma that typically affects both eyes, causes reduced visual acuity and restricted visual fields, and leads to blindness if untreated. PCG often presents with cloudiness of the cornea and buphthalmos; other common findings include increased intraocular pressure, progressive glaucomatous optic atrophy, thinning of the anterior sclera, edema, iris atrophy, and an unusually deep anterior chamber. Epiphora, photophobia, and blepharospasm are frequent symptoms. Classic PCG does not include structural defects of the anterior chamber that are found with anterior segment dysgenesis. Most commonly, PCG is diagnosed within the first year of life. Pathogenic changes in CYP1B1 are known to cause PCG and can also be found in individuals with Peters anomaly, juvenile open-angle glaucoma, and primary open-angle glaucoma.

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. Nearly half of affected individuals develop glaucoma, which can be early-onset. Abnormal development of the anterior segment of the eye manifests as iris hypoplasia or corectopia and anteriorly displaced Schwalbe’s line with iridocorneal adhesions. Affected individuals may exhibit different degrees of abnormality in each eye.

Pathogenic changes in CYP1B1 account for 20-100% of cases of familial PCG and 10-27% of cases of simplex PCG. Whether a molecular diagnosis will be obtained through testing of CYP1B1 varies greatly and depends on the characteristics of the individual tested. The likelihood of identifying pathogenic changes in CYP1B1 increases when an individual is bilaterally affected and has a family history of PCG, known parental consanguinity, and/or severe disease.

Pathogenic changes in FOXC1 and PITX2 account for 15-40% of ARS cases. Approximately half of individuals with ARS develop glaucoma.

Primary congenital glaucoma is inherited in an autosomal recessive manner, and Axenfeld-Rieger syndrome is inherited in an autosomal dominant manner.

Penetrance of glaucoma (primary congenital, juvenile open-angle, or primary open-angle) is about 90% in individuals with pathogenic variants in CYP1B1. ARS is a completely penetrant disorder with approximately half of affected individuals developing glaucoma.

The incidence of PCG is estimated to be between 1:10,000 and 1:70,000 in the United States and Western European countries. In specific populations (including the Middle East and a part of India), the incidence can be as high as between 1:1,250 and 1:3,300.

The prevalence of Axenfeld-Rieger syndrome is estimated at 1 in 200,000 individuals, with approximately half of affected individuals developing glaucoma.

  1. Abdolrahimzadeh, S, et al. Rare Diseases Leading to Childhood Glaucoma: Epidemiology, Pathophysiogenesis, and Management. Biomed Res Int. 2015; 2015:781294. PMID: 26451378
  2. Abu-Amero, KK, Edward, DP. Primary Congenital Glaucoma. 2004 Sep 30. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301314
  3. Alward, WL. Axenfeld-Rieger syndrome in the age of molecular genetics. Am. J. Ophthalmol. 2000; 130(1):107-15. PMID: 11004268
  4. 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
  5. Dressler, S, et al. Dental and Craniofacial Anomalies Associated with Axenfeld-Rieger Syndrome with PITX2 Mutation. Case Rep Med. 2010; 2010:621984. PMID: 20339518
  6. Idrees, F, et al. A review of anterior segment dysgeneses. Surv Ophthalmol. 2006; 51(3):213-31. PMID: 16644364
  7. Orphanet. Axenfeld-Rieger syndrome. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=782 Accessed February 2016.
  8. Reis, LM, et al. PITX2 and FOXC1 spectrum of mutations in ocular syndromes. Eur. J. Hum. Genet. 2012; 20(12):1224-33. PMID: 22569110
  9. 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
  10. Suri, F, et al. Variable expressivity and high penetrance of CYP1B1 mutations associated with primary congenital glaucoma. Ophthalmology. 2009; 116(11):2101-9. PMID: 19744731
  11. 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
  12. Weisschuh, N, et al. Clinical utility gene card for: Axenfeld-Rieger syndrome. Eur. J. Hum. Genet. 2011; 19(3). PMID: 20940740
  13. 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
  14. Yu, Chan, JY, et al. Review on the Management of Primary Congenital Glaucoma. J Curr Glaucoma Pract. 2015; 9(3):92-9. PMID: 26997844

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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
CYP1B1 NM_000104.3
FOXC1 NM_001453.2
PITX2 NM_153427.2; NM_000325.5; NM_153426.2