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Syndromic Microphthalmia via the OTX2 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
OTX2 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9153OTX281479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Jamie Fox, PhD

Clinical Features and Genetics

Clinical Features

Anophthalmia (A; absence of a globe in the orbit) and microphthalmia (M; reduced size of the globe) are severe and rare developmental defects of the globe with an estimated incidence of 0.2–0.4/10 000 and ~1.5/10 000 live births, respectively (Källén and Tornqvist 2005). Both A/M may be unilateral or bilateral, and over 50% of A/M affected individuals have systemic abnormalities such as hypothalamic–pituitary disorder, mild dysmorphic facial features and short stature, urogenital anomalies, cryptorchidism and/or micropenis in males, developmental delay, seizures, oesophageal atresia or tracheooesophageal fistula and hearing loss (Ragge et al. 2005), but only 25% of these are part of distinct and well-defined syndromes (Bakrania et al. 2007). Unilateral A/M cases often have developmental anomalies of the other eye; including coloboma, lens, and optic nerve (Ragge et al. 2007).


Heterozygous loss-of-function variants in the gene OTX2 result in an incompletely penetrant, haploinsufficiency disorder (Mortensen et al. 2015). Affected individuals exhibit a spectrum of symptoms, which range from developmental defects in the eyes and/or pituitary gland to acephaly. A high degree of mosaicism also had been reported (Ragge et al. 2005). So far, over 50 pathogenic variants (Missense/nonsense, splicing, small as well as gross insertions and deletions) have been reported in OTX2, which are causative for ocular malformations (Human Gene Mutation Database). De novo mutations in OTX2 have been frequently reported  (Henderson et al. 2009; Slavotinek et al. 2014; Dateki et al. 2008).

OTX2 (Orthodenticle homeobox 2), which is located at 14q22.3, is a bicoid class homeobox family transcription factor that is required for the normal development of the forebrain, eye, and pituitary gland (Diaczok et al. 2008; Mortensen et al. 2015). A/M may also be caused by pathogenic variants in the SOX2 gene which accounts for 10-20% of cases (Bakrania et al. 2007, Reis et al. 2010). OTX2 pathogenic variants account for 2-3% of A/M cases (Wyatt et al. 2008).

Clinical Sensitivity - Sequencing with CNV PGxome

OTX2 pathogenic variants account for 2-3% of microphthalmia/ anophthalmia cases (Wyatt et al. 2008).

Testing Strategy

This test provides full coverage of all coding exons of the OTX2 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Patients with microphthalmia/anophthalmia and pituitary anomalies are candidates.


Official Gene Symbol OMIM ID
OTX2 600037
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Microphthalmia Syndromic 5 AD 610125

Related Tests

Agnathia-Otocephaly Complex Panel
Leber Congenital Amaurosis Panel


  • Bakrania P. et al. 2007. The British Journal of Ophthalmology. 91: 1471-6. PubMed ID: 17522144
  • Dateki S, Fukami M, Sato N, Muroya K, Adachi M, Ogata T. 2008. OTX2 Mutation in a Patient with Anophthalmia, Short Stature, and Partial Growth Hormone Deficiency: Functional Studies Using the IRBP, HESX1, and POU1F1 Promoters. The Journal of Clinical Endocrinology & Metabolism 93: 36973702. PubMed ID: 18628516
  • Diaczok D, Romero C, Zunich J, Marshall I, Radovick S. 2008. A Novel Dominant Negative Mutation of OTX2 Associated with Combined Pituitary Hormone Deficiency. J Clin Endocrinol Metab 93: 43514359. PubMed ID: 18728160
  • Henderson RH, Williamson KA, Kennedy JS, Webster AR, Holder GE, Robson AG, FitzPatrick DR, Heyningen V van, Moore AT. 2009. A rare de novo nonsense mutation in OTX2 causes early onset retinal dystrophy and pituitary dysfunction. Molecular vision 15: 2442-2447. PubMed ID: 19956411
  • Human Gene Mutation Database (Bio-base).
  • Klln B, Tornqvist K. 2005. European Journal of Epidemiology. 20: 345350. PubMed ID: 15971507
  • Mortensen AH, Schade V, Lamonerie T, Camper SA. 2015. Deletion of OTX2 in neural ectoderm delays anterior pituitary development. Hum. Mol. Genet. 24: 939953. PubMed ID: 25315894
  • Ragge N.K. et al. 2005. American Journal of Medical Genetics. Part A. 135: 1-7; discussion 8. PubMed ID: 15812812
  • Ragge N.K. et al. 2007. Eye (london, England). 21: 1290-300. PubMed ID: 17914432
  • Ragge NK, Brown AG, Poloschek CM, Lorenz B, Henderson RA, Clarke MP, Russell-Eggitt I, Fielder A, Gerrelli D, Martinez-Barbera JP, others. 2005. Heterozygous mutations of OTX2 cause severe ocular malformations. The American Journal of Human Genetics 76: 10081022. PubMed ID: 15846561
  • Reis L.M. et al. 2010. Molecular Vision 16: 768-73. PubMed ID: 20454695
  • Slavotinek AM, Garcia ST, Chandratillake G, Bardakjian T, Ullah E, Wu D, Umeda K, Lao R, Tang PL-F, Wan E, Madireddy L, Lyalina S, Mendelsohn BA, Dugan S, Tirch J, Tischler R, Harris J, Clark MJ, Chervitz S, Patwardhan A, West JM, Ursell P, de Alba Campomanes A, Schneider A, Kwok P, Baranzini S, Chen RO. 2014. Exome sequencing in 32 patients with anophthalmia/microphthalmia and developmental eye defects. Clin. Genet. PubMed ID: 25457163
  • Wyatt A. et al. 2008. Human Mutation 29: E278E283. PubMed ID: 18781617


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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