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

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
  • Deletion/Duplication Analysis

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
  • Deletion/Duplication Analysis
  • 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

ALDH1A3, BCOR, BMP4, BMP7, COX7B, CRYBA4, FOXE3, GDF6, HCCS, MITF, NAA10, NDUFB11, OTX2, PAX6, PRSS56, RAX, SALL1, SHH, SIX6, SOX2, STRA6, TENM3, VSX2 (CHX10)
  • Absent or underdeveloped eyes and eye tissue resulting in reduced axial length and narrow palpebreal fissures
  • Coloboma, cataract, glaucoma or microcornia in addition to overall eye underdevelopment
  • Associated findings such as cleft lip/palate, seizures, brain malformations, learning and developmental disabilities
  • Chromosome aberrations, as seen in approximately 1/4 of individuals with A/M
  • Next-Gen Sequencing
  • Exon Array Dx

Ordering

J957
4 weeks
2-5 mL Blood - Lavender Top Tube
Buccal Swab

Billing

81479x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Verma et al. (2007) Orphanet J Rare Dis 2 :47 (PMID: 18039390)
  2. Chassaing et al. (2014) Clinical Genetics 86 (4):326-34 (PMID: 24033328)
  3. Bardakjian et al., (2015) GeneReviews® https://www.ncbi.nlm.nih.gov/books/NBK1378/
  4. Deml et al. (2016) Eur. J. Hum. Genet. 24 (4):535-41 (PMID: 26130484)
  5. Slavotinek et al. (2011) Mol. Genet. Metab. 104 (4):448-56 (PMID: 22005280)
  6. Abouzeid et al. (2014) Hum. Mutat. 35 (8):949-53 (PMID: 24777706)
  7. Ng et al. (2004) Nature Genetics 36 (4):411-6 (PMID: 15004558)
  8. Jimenez et al. (2011) BMC Med. Genet. 12 :172 (PMID: 22204637)
  9. Reis et al. (2011) Human Genetics 130 (4):495-504 (PMID: 21340693)
  10. Indrieri et al. (2012) Am. J. Hum. Genet. 91 (5):942-9 (PMID: 23122588)
  11. Billingsley et al. (2006) Am. J. Hum. Genet.79 (4):702-9 (PMID: 16960806)
  12. Reis et al. (2010) Am. J. Med. Genet. Part A 152A (3):582-90 (PMID: 20140963)
  13. Ye et al. (2010) Human Molecular Genetics 19 (2):287-98 (PMID: 19864492)
  14. van Rahden et al. (2014) Orphanet J Rare Dis 9 :53 (PMID: 24735900)
  15. George et al. (2016) Am. J. Hum. Genet. 99 (6):1388-1394 (PMID: 27889061)
  16. Esmailpour et al. (2014) Journal Of Medical Genetics 51 (3):185-96 (PMID: 24431331)
  17. van Rahden et al. (2015) American Journal Of Human Genetics 96 (4):640-50 (PMID: 25772934)
  18. Gal et al. (2011) Am. J. Hum. Genet. 88 (3):382-90 (PMID: 21397065)
  19. Bardakjian et al. (2009) BMC Med. Genet. 10 :137 (PMID: 20003547)
  20. Schimmenti et al. (2003) Am. J. Med. Genet. A 116A (3):215-21 (PMID: 12503095)
  21. Aldahmesh et al. (2013) Clinical Genetics 84 (2):198-9 (PMID: 23167593)
  22. Reis et al. (2015) Birth Defects Res. C Embryo Today 105 (2):96-113 (PMID: 26046913)
  23. Gerth-Kahlert et al. (2013) Molecular Genetics & Genomic Medicine 1 (1):15-31 (PMID: 24498598)
  24. Chassaing et al. (2016) Am. J. Med. Genet. A 170 (7):1895-8 (PMID: 27103084)
  25. Reis et al. (2011) Mol. Vis. 17 :2527-32 (PMID: 21976963)
  26. Wyatt et al. (2010) Hum. Mutat. 31 (7):781-7 (PMID: 20506283)