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  • Test code: 05142
  • 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 Microphthalmia/Anophthalmia Disorders Panel

Test description

The Invitae Microphthalmia/Anophthalmia Panel analyzes up to 21 genes associated with microphthalmia and/or anophthalmia, which are characterized by an absent or abnormally small eye with a short axial length. These genes were selected based on the available evidence to date to provide Invitae’s broadest test for microphthalmia and/or anophthalmia.

Panel testing allows for an efficient evaluation of several potential genes based on a single clinical indication for testing. Early genetic testing for the underlying cause of microphthalmia and/or anophthalmia may assist in determining whether the condition is isolated or part of a syndrome and can help guide future treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives.

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Primary panel (17 genes)

ALDH1A3 BCOR BMP4 FOXE3 GDF6 MAB21L2 MFRP OTX2 PAX2 PRSS56 PXDN RARB RAX SHH SOX2 STRA6 VSX2

Add-on Preliminary-evidence Genes for Microphthalmia/Anophthalmia Disorders (4 genes)

In addition to the primary panel, clinicians can also choose to include three genes that have preliminary evidence of association with microphthalmia/anophthalmia. At this time, the association of these five genes with microphthalmia/anophthalmia remains uncertain. However, some clinicians may wish to include genes that may prove to be clinically significant in the future. Visit our Preliminary-evidence genes page to learn more.

GDF3 HESX1 SALL4 VAX1

Alternative tests to consider

Microphthalmia and/or anophthalmia can also be found in patients with aniridia, congenital cataracts, or Axenfeld-Rieger syndrome. In the presence of any of these features, an alternate panel may be more appropriate.

  • anophthalmia
  • microphthalmia
    • isolated microphthalmia
    • Lenz microphthalmia syndrome
    • microphthalmia with coloboma
    • syndromic microphthalmia
  • microphthalmia/anophthalmia/coloboma (MAC) spectrum

Microphthalmia is a condition in which the globe of the eye has a total axial length that is at least two standard deviations below the mean for age, and anophthalmia refers to complete absence of the globe. The terms posterior microphthalmia and anophthalmia are sometimes used interchangeably. This structural anomaly is part of the microphthalmia/anophthalmia/coloboma (MAC) spectrum of disorders and can lead to significant disability. Approximately 81% of individuals with microphthalmia have reduced vision. Hypertelorism and hemifacial microsomia can also be seen in individuals with microphthalmia, and severely affected individuals may have hypoplasia of the orbit. The disorder may affect one or both eyes. MAC disorders are responsible for 15%–20% of blindness worldwide.

The Invitae Microphthalmia/Anophthalmia Panel may identify a molecular cause of disease more than 30% of cases of microphthalmia/anophthalmia (PMID: 24033328, 20301552).

Gene% of MAC attributed to this gene
ALDH1A3 Unknown
BCOR >1%
BMP4 2%
FOXE3 1-2.5%
GDF6 1%
MAB21L2 Unknown
MFRP Unknown
PAX2 Unknown
PRSS56 Unknown
PXDN Rare
OTX2 2-5%
RARB Unknown
RAX 3%
SHH Rare
SOX2 12-20%
STRA6 >1%
VSX2 Rare

Inherited microphthalmia can occur in several inheritance patterns, including autosomal dominant, autosomal recessive, and X-linked dominant.

Penetrance of microphthalmia and/or anophthalmia varies by gene, and ranges from low to complete.

The combined prevalence of anophthalmia and microphthalmia ranges from 1 in 7,000 to 1 in 30,000 individuals. The prevalence of microphthalmia was estimated at 2–17 per 100,000 individuals in a population from the United Kingdom.

Both single-gene and chromosomal abnormalities can cause microphthalmia/anophthalmia, which may be isolated, associated with other ocular abnormalities, or a component of a well-defined syndrome. A genetic evaluation is recommended for affected individuals to determine whether the condition is isolated or a component of a broader ocular or multisystem disorder, a distinction that may be difficult to elucidate at birth.

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
ALDH1A3 NM_000693.3
BCOR NM_017745.5
BMP4 NM_001202.3
FOXE3 NM_012186.2
GDF3 NM_020634.1
GDF6 NM_001001557.2
HESX1 NM_003865.2
MAB21L2 NM_006439.4
MFRP NM_031433.3
OTX2 NM_172337.2
PAX2 NM_003988.3
PRSS56 NM_001195129.1
PXDN NM_012293.2
RARB NM_000965.4
RAX NM_013435.2
SALL4 NM_020436.3
SHH NM_000193.2
SOX2 NM_003106.3
STRA6 NM_022369.3
VAX1 NM_001112704.1
VSX2 NM_182894.2