Anophthalmia

Several developmental eye disorders have a known genetic basis, including microphthalmia and anophthalmia. Anophthalmia is the complete absence of the globe, or bulb, of the eye and hence the most severe structural eye malformation. A milder form is microphthalmia, where the total axial length of the eye globe is at least two standard deviations below the mean for age. Simple microphthalmos refers to a structurally normal eye with short total axial length. In each of these conditions, the eyelids, conjunctiva and lacrimal apparatus are normal. In complex microphthalmia, additional abnormalities are present and may include anterior segment dysgenesis, cataract, persistent hyperplastic primary vitreous, chorioretinal coloboma and/or retinal dysplasia. Anophthalmia/microphthalmia has been observed in association with various genetic syndromes and approximately 25% of individuals with anophthalmia/microphthalmia have identifiable chromosomal abnormalities (Forrester 2006). Mutations in the SOX2, OTX2, SIX6 and VSX2 genes leading to haploinsufficiency may be associated with anophthalmia and microphthalmia. SOX2 mutations are also known to be associated with hearing loss, developmental delay, esophageal atresia, genitourinary abnormalities, myopathy, and spastic diplegia. OTX2 mutations have been reported in patients with anophthalmia/microphthalmia associated with brain malformations and pituitary insufficiency. VSX2 mutations are usually associated with isolated ocular finding without other systemic malformations. Heterozygous deletions of the entire SIX6 gene have been seen in some cases of bilateral anophthalmia due to interstitial chromosome deletions. PAX6 mutations have also been associated with anophthalmia (analysis of PAX6 is available, for further information see http://www.genedx.com).

Tests Available

Forms and Documents

Test Details

OTX2
  • Confirmation of a clinical diagnosis
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

343
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81479x1
No
Yes
  • 743.1 Microphthalmos, Dysplasia of eye, Hypoplasia of eye, Rudimentary eye
  • 743.11 Simple microphthalmos
  • 743.9 Specified congenital anomalies of anterior chamber, chamber angle, and related structures.
* For price inquiries please email zebras@genedx.com

References

  1. Gallardo ME et al., (1999) Genomic 61:82
  2. Gallardo, ME et al., (2004) Am J Med Genet 129A:92
  3. Bennett CP (1991) J Med Genet 1991;28:280-1
  4. Elliott J et al., (1993) 30(3):251-2
  5. Wyatt A et al., (2008) Hum Mutat. (2008) 29(11):E278-83
  6. Ragge NK et al., (2007) Eye 21(10):1290-300
  7. Bar-Yosef U et al., (2004) Hum Genet 115: 302–309
  8. Schneider et al. (2009) Am J Med Genet 149A(12)2706-2715
  9. Bakrania et al. (2007) Br J Ophthalmol 91:1471-17476
  10. E. Ferda Percin et al., (2000) Nat Genet 25(4):397-401
  11. Ragge NK et al., (2005) Am J Hum Genet. 276(6):1008-22
  12. Aijaz S et al (2004) Invest Ophthalmol Vis Sci. 45(11):3871-6
  13. Fantes, J et al (2003) Nature Genetics 33:462
  14. Hagstrom SA et al. (2005) Am J Med Genet (2005) 138(2):95
  15. Williamson, KA et al. (2006) Hum Mol Genet 15(9):1413
  16. Forrester and Merz (2006) Birth Defects Res A Clin Mol Terato 76:187-192

Forms and Documents

Test Details

DCDC1, ELP4, PAX6, WT1
  • Confirmation of clinical diagnosis
  • Determination of the molecular basis of aniridia in patients at risk for Wilms tumor (Differentiating PAX6 related aniridia from WAGR syndrome)
  • Prenatal diagnosis
  • Capillary Sequencing
  • Exon Array CGH

Ordering

491
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 743.45 Aniridia
  • 743.9 Specified congenital anomalies of anterior chamber, chamber angle, and related structures.
* For price inquiries please email zebras@genedx.com

References

  1. Glaser T et al. (1994) Nat Genet 7:463
  2. Tzoulaki I et al. BMC Genetics (2005) 6:27
  3. Gronskov K et al. (2001) Hum Genet 109:11
  4. Vincent MC et al. (2002) Eur J of Hum Genet 11:163
  5. Redeker EJ et al, (2008); Mol Vis. May 7;14:836-40

Forms and Documents

Test Details

OTX2, SOX2, VSX2 (CHX10)
  • Full sequencing testing for fetuses with prenatal ultrasound findings suggestive of anophthalmia/microphthalmia
  • Exon Array CGH
  • Next-Gen Sequencing

Ordering

428
2-3 weeks
20 mL Amniotic Fluid
20 mg CVS|2 T25 flasks of cultured amniocytes|2 T25 flasks of cultured chorionic villi|3 Ug DNA Concentration

Billing

81265x1, 81479x3
No
Yes
  • 655.2 Hereditary disease in family possibly affecting fetus [0,1,3]
  • 655.8 Other known or suspected fetal abnormality, not elsewhere classified [0,1,3] Suspected damage to fetus from: environmental toxins intrauterine contraceptive device
* For price inquiries please email zebras@genedx.com

References

  1. Forrester and Merz (2006) Birth Defects Res A Clin Mol Terato 76:187-192
  2. Williamson, KA et al. (2006) Hum Mol Genet 15(9):1413
  3. Hagstrom SA et al. (2005) Am J Med Genet (2005) 138(2):95
  4. Fantes, J et al (2003) Nature Genetics 33:462
  5. Gallardo ME et al., (1999) Genomic 61:82
  6. Gallardo, ME et al., (2004) Am J Med Genet 129A:92
  7. Bennett CP (1991) J Med Genet 1991;28:280-1
  8. Elliott J et al., (1993) 30(3):251-2
  9. Wyatt A et al., (2008) Hum Mutat. (2008) 29(11):E278-83
  10. Ragge NK et al., (2007) Eye 21(10):1290-300
  11. Bar-Yosef U et al., (2004) Hum Genet 115: 302–309
  12. Schneider et al. (2009) Am J Med Genet 149A(12)2706-2715
  13. Bakrania et al. (2007) Br J Ophthalmol 91:1471-17476
  14. E. Ferda Percin et al., (2000) Nat Genet 25(4):397-401
  15. Aijaz S et al (2004) Invest Ophthalmol Vis Sci. 45(11):3871-6
  16. Ragge NK et al., (2005) Am J Hum Genet. 276(6):1008-22

Forms and Documents

Test Details

RAX
  • Confirmation of a clinical diagnosis
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

509
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 743.1 Microphthalmos, Dysplasia of eye, Hypoplasia of eye, Rudimentary eye
  • 743.11 Simple microphthalmos
  • 743.9 Specified congenital anomalies of anterior chamber, chamber angle, and related structures.
* For price inquiries please email zebras@genedx.com

References

  1. White et al., (2008) Mol Vis.14:2458-65
  2. West et al., (2009) Am J Med Genet A. 149A(3):539-42
  3. Passuto et al., (2007) Am J Hum Genet. 80(3):550-60
  4. Golzio et al., (2007) Am J Hum Genet. 80(6):1179-87
  5. Chassaing et al., (2009) Hum Mutat. 30(5):E673-81
  6. Aijaz S et al (2004) Invest Ophthalmol Vis Sci. 45(11):3871-6
  7. Ragge NK et al., (2005) Am J Hum Genet. 276(6):1008-22
  8. E. Ferda Percin et al., (2000) Nat Genet 25(4):397-401
  9. Schneider et al. (2009) Am J Med Genet 149A(12)2706-2715
  10. Bakrania et al. (2007) Br J Ophthalmol 91:1471-17476
  11. Ragge NK et al., (2007) Eye 21(10):1290-300
  12. Bar-Yosef U et al., (2004) Hum Genet 115: 302–309
  13. Wyatt A et al., (2008) Hum Mutat. (2008) 29(11):E278-83
  14. Bennett CP (1991) J Med Genet 1991;28:280-1
  15. Elliott J et al., (1993) 30(3):251-2
  16. Gallardo, ME et al., (2004) Am J Med Genet 129A:92
  17. Gallardo ME et al., (1999) Genomic 61:82
  18. Fantes, J et al (2003) Nature Genetics 33:462
  19. Hagstrom SA et al. (2005) Am J Med Genet (2005) 138(2):95
  20. London et al. (2009) Molecular Vision 15:162-167
  21. Voronina et al. (2004) Hum Mol Genet 13(3):315-22
  22. Lequeux et al. (2008) Clin Genet 74(4):392-395
  23. Forrester and Merz (2006) Birth Defects Res A Clin Mol Terato 76:187-192
  24. Williamson, KA et al. (2006) Hum Mol Genet 15(9):1413

Forms and Documents

Test Details

SOX2
  • Confirmation of a clinical diagnosis
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

132
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81479x1
No
Yes
  • 743.1 Microphthalmos, Dysplasia of eye, Hypoplasia of eye, Rudimentary eye
  • 743.11 Simple microphthalmos
  • 743.9 Specified congenital anomalies of anterior chamber, chamber angle, and related structures.
* For price inquiries please email zebras@genedx.com

References

  1. Williamson, KA et al. (2006) Hum Mol Genet 15(9):141
  2. Hagstrom SA et al. (2005) Am J Med Genet (2005) 138(2):95
  3. Fantes, J et al (2003) Nature Genetics 33:462
  4. Gallardo ME et al., (1999) Genomic 61:82
  5. Gallardo, ME et al., (2004) Am J Med Genet 129A:92
  6. Bennett CP (1991) J Med Genet 1991;28:280-1
  7. Elliott J et al., (1993) 30(3):251-2
  8. Wyatt A et al., (2008) Hum Mutat. (2008) 29(11):E278-83
  9. E. Ferda Percin et al., (2000) Nat Genet 25(4):397-401. Aijaz S et al (2004) Invest Ophthalmol Vis Sci. 45(11):3871-6. Ragge NK et al., (2005) Am J Hum Genet. 276(6):1008-22
  10. Bakrania et al. (2007) Br J Ophthalmol 91:1471-17476
  11. Schneider et al. (2009) Am J Med Genet 149A(12)2706-2715
  12. Ragge NK et al., (2007) Eye 21(10):1290-300; Bar-Yosef U et al., (2004) Hum Genet 115: 302–309
  13. Forrester and Merz (2006) Birth Defects Res A Clin Mol Terato 76:187-192.

Forms and Documents

Test Details

STRA6
  • Confirmation of a clinical diagnosis
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

516
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 743.1 Microphthalmos, Dysplasia of eye, Hypoplasia of eye, Rudimentary eye
  • 743.11 Simple microphthalmos
  • 743.9 Specified congenital anomalies of anterior chamber, chamber angle, and related structures.
* For price inquiries please email zebras@genedx.com

References

  1. Forrester and Merz (2006) Birth Defects Res A Clin Mol Terato 76:187-192
  2. E. Ferda Percin et al., (2000) Nat Genet 25(4):397-401
  3. Aijaz S et al (2004) Invest Ophthalmol Vis Sci. 45(11):3871-6
  4. Ragge NK et al., (2005) Am J Hum Genet. 276(6):1008-22
  5. White et al., (2008) Mol Vis.14:2458-65
  6. Golzio et al., (2007) Am J Hum Genet. 80(6):1179-87
  7. West et al., (2009) Am J Med Genet A. 149A(3):539-42
  8. Chassaing et al., (2009) Hum Mutat. 30(5):E673-81
  9. Passuto et al., (2007) Am J Hum Genet. 80(3):550-60
  10. Bakrania et al. (2007) Br J Ophthalmol 91:1471-17476
  11. Schneider et al. (2009) Am J Med Genet 149A(12)2706-2715
  12. Bar-Yosef U et al., (2004) Hum Genet 115: 302–309
  13. Ragge NK et al., (2007) Eye 21(10):1290-300
  14. Wyatt A et al., (2008) Hum Mutat. (2008) 29(11):E278-83
  15. Elliott J et al., (1993) 30(3):251-2
  16. Bennett CP (1991) J Med Genet 1991;28:280-1
  17. Gallardo, ME et al., (2004) Am J Med Genet 129A:92
  18. Gallardo ME et al., (1999) Genomic 61:82
  19. Fantes, J et al (2003) Nature Genetics 33:462
  20. Hagstrom SA et al. (2005) Am J Med Genet (2005) 138(2):95
  21. Williamson, KA et al. (2006) Hum Mol Genet 15(9):1413
  22. London et al. (2009) Molecular Vision 15:162-167
  23. Lequeux et al. (2008) Clin Genet 74(4):392-395
  24. Voronina et al. (2004) Hum Mol Genet 13(3):315-22

Forms and Documents

Test Details

VSX2 (CHX10)
  • Confirmation of a clinical diagnosis
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

344
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81479x1
No
Yes
  • 743.1 Microphthalmos, Dysplasia of eye, Hypoplasia of eye, Rudimentary eye
  • 743.11 Simple microphthalmos
  • 743.9 Specified congenital anomalies of anterior chamber, chamber angle, and related structures.
* For price inquiries please email zebras@genedx.com

References

  1. Schneider et al. (2009) Am J Med Genet 149A(12)2706-2715
  2. Bakrania et al. (2007) Br J Ophthalmol 91:1471-17476
  3. E. Ferda Percin et al., (2000) Nat Genet 25(4):397-401
  4. Aijaz S et al (2004) Invest Ophthalmol Vis Sci. 45(11):3871-6
  5. Ragge NK et al., (2005) Am J Hum Genet. 276(6):1008-22
  6. Bar-Yosef U et al., (2004) Hum Genet 115: 302–309
  7. Ragge NK et al., (2007) Eye 21(10):1290-300
  8. Wyatt A et al., (2008) Hum Mutat. (2008) 29(11):E278-83
  9. Elliott J et al., (1993) 30(3):251-2
  10. Bennett CP (1991) J Med Genet 1991;28:280-1
  11. Gallardo, ME et al., (2004) Am J Med Genet 129A:92
  12. Fantes, J et al (2003) Nature Genetics 33:462
  13. Gallardo ME et al., (1999) Genomic 61:82
  14. Hagstrom SA et al. (2005) Am J Med Genet (2005) 138(2):95
  15. Forrester and Merz (2006) Birth Defects Res A Clin Mol Terato 76:187-192
  16. Williamson, KA et al. (2006) Hum Mol Genet 15(9):1413