Invitae Microphthalmia/Anophthalmia Disorders Panel


Test description

The Invitae Microphthalmia/Anophthalmia Disorders Panel analyzes four genes associated with microphthalmia, a condition characterized by an abnormally small eye with a short axial length. These genes were curated based on the available evidence to date to provide a comprehensive analysis for inherited microphthalmia.

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 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 (4 genes)


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.

  • Microphthalmia/anophthalmia/coloboma (MAC) spectrum
    • Retinal dystrophy early-onset, with or without pituitary dysfunction
    • Syndromic microphthalmia-2
    • Syndromic microphthalmia-5
    • Syndromic microphthalmia-3
    • Microphthalmia with coloboma-3
    • Isolated microphthalmia-2
    • Optic nerve hypoplasia and abnormalities of the central nervous system

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. 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.

SOX2 pathogenic variants account for approximately 15%–20% of microphthalmia cases. Pathogenic variants in OTX2 have been reported in about 2%–5% of microphthalmia cases while variants in BCOR and VSX2 each account for <1% of microphthalmia cases.

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

BCOR has complete penetrance. The penetrance of the OTX2, SOX2, and VSX2 genes is not known.

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, 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, 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
BCOR NM_017745.5
OTX2 NM_172337.2
SOX2 NM_003106.3
VSX2 NM_182894.2