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PubMed This is a summary of 14 peer-reviewed journal articles Updated
Ophthalmology · Microphthalmia, Anophthalmia, and Coloboma (MAC)

Confirming 'Isolated' MAC: The Complete Workup

At a Glance

To confirm if microphthalmia, anophthalmia, or coloboma (MAC) is isolated or part of a larger syndrome, a comprehensive medical workup is essential. This includes a brain MRI, heart and kidney ultrasounds, baseline hearing tests, and advanced genetic testing like Whole Exome Sequencing.

When navigating Microphthalmia, Anophthalmia, or Coloboma (MAC), an urgent question is, “Is this just an eye issue, or is it part of something bigger?”

In the medical world, this is the difference between isolated MAC (only the eyes are affected) and syndromic MAC (the eye condition is part of a larger syndrome involving other organs) [1][2]. While it may be tempting to focus solely on the eyes, a complete systemic workup is vital. Many syndromes are “silent” initially, meaning internal issues like heart or kidney defects might not be visible without specialized testing [3][4].

Why a Full Workup is Mandatory

Even if an eye doctor says the condition “looks isolated,” current medical standards recommend looking deeper. Up to 55% of children with MAC may have at least one other finding or an underlying genetic syndrome [3][5].

While discovering that a condition involves other organs can be frightening, it is ultimately empowering information. It allows your care team to monitor growth, heart health, and development proactively, rather than waiting for an emergency to appear [6].

The Diagnostic Path: Systems to Check

A “complete” evaluation involves more than just an eye exam. Your team should check the following systems:

  • The Brain: A Brain MRI is used to look for structural changes, such as a missing corpus callosum (the bridge between the two sides of the brain) or anomalies in the pituitary gland, which controls growth and hormones [7][8].
  • The Heart: An echocardiogram (ultrasound of the heart) checks for “silent” cardiac defects that are common in some MAC-related syndromes [9].
  • The Kidneys: A renal ultrasound ensures the kidneys are formed and positioned correctly [2].
  • Hearing: A baseline hearing test (often a BAER test) is recommended, as some genetic switches that build the eye also help build the inner ear [8].

The Genetic Testing Ladder

Genetic testing is the “gold standard” for confirming if MAC is isolated or syndromic. Doctors typically follow a specific pathway:

  1. Clinical Phenotyping: Before testing, doctors perform a detailed physical exam (deep phenotyping) to look for subtle clues like cleft palate or limb differences [10].
  2. Multigene Panels: These tests look at a specific “bucket” of genes known to cause eye issues. They are efficient but can miss newer or rarer genetic causes [11].
  3. Whole Exome Sequencing (WES): If a panel is negative, WES is often the next step. It looks at all the protein-coding parts of your DNA and has a higher “yield” (success rate) for finding an answer in complex cases [9][12]. Note: WES is highly detailed, and results can take several weeks to months to return.

Completeness Checklist

Use this list to track the diagnostic journey and ensure no stone is left unturned:

  • [ ] Comprehensive Eye Exam: Dilated exam of both eyes to check for “silent” colobomas in the healthy-looking eye [13].
  • [ ] Brain & Orbit MRI: To check the optic nerves and brain structure [14].
  • [ ] Renal (Kidney) Ultrasound: To rule out internal anomalies [2].
  • [ ] Echocardiogram (Heart Ultrasound): To check for cardiac involvement [9].
  • [ ] Audiology (Hearing) Screening: Baseline test to rule out sensorineural hearing loss [8].
  • [ ] Genetics Consultation: Referral to a medical geneticist for WES or panel testing [3].
  • [ ] Endocrine Evaluation: Especially if the MRI showed any pituitary issues [8].

Common questions in this guide

Why does my child need a full body workup for an eye condition?
Up to 55% of children with MAC may have an underlying genetic syndrome or structural differences in other organs. A complete workup checks for silent internal conditions in the heart, kidneys, and brain so they can be monitored and managed proactively.
What is the difference between isolated and syndromic MAC?
Isolated MAC means the condition affects only the eyes. Syndromic MAC means the eye anomalies are part of a larger genetic syndrome that involves other organs or bodily systems.
What imaging tests are required for a complete MAC diagnosis?
A thorough evaluation usually includes a brain and orbit MRI to check nerve and brain structures, an echocardiogram to check the heart, and a renal ultrasound to evaluate the kidneys.
Is a hearing test necessary if my baby responds to sound?
Yes, a baseline hearing test is recommended even if hearing seems normal. The genetic pathways that help develop the eye are closely linked to those that build the inner ear, making hidden hearing loss a possibility.
What type of genetic testing is best for MAC?
Doctors typically begin with targeted multigene panels that look at known eye-related genes. If those tests do not provide answers, Whole Exome Sequencing (WES) may be recommended to examine all protein-coding DNA.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Since over half of MAC cases can involve other organs, what specific schedule of scans (heart, kidney, brain) will you be ordering?
  2. 2.Can we consult with a medical geneticist to discuss whether Whole Exome Sequencing (WES) is a better choice than a targeted eye panel?
  3. 3.If a brain MRI is done, will the radiologist be specifically looking at the pituitary gland and the corpus callosum?
  4. 4.Should there be a baseline hearing test even if responses to sound seem normal?
  5. 5.What 'deep phenotyping' steps are you taking to ensure we haven't missed subtle signs of a syndrome, like small limb differences or heart murmurs?

Questions For You

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References

References (14)
  1. 1

    Identification of a possible association of JAK2 in development of microphthalmia, anophthalmia, and coloboma (MAC) complex in a child with 9p deletion and duplication.

    Leung KCP, Ko TCS

    Ophthalmic genetics 2020; (41(4)):373-376 doi:10.1080/13816810.2020.1776338.

    PMID: 32506980
  2. 2

    Eyes on CHARGE syndrome: Roles of CHD7 in ocular development.

    Krueger LA, Morris AC

    Frontiers in cell and developmental biology 2022; (10()):994412 doi:10.3389/fcell.2022.994412.

    PMID: 36172288
  3. 3

    Epidemiology of anophthalmia and microphthalmia: Prevalence and patterns in Texas, 1999-2009.

    Chambers TM, Agopian AJ, Lewis RA, et al.

    American journal of medical genetics. Part A 2018; (176(9)):1810-1818 doi:10.1002/ajmg.a.40352.

    PMID: 30070760
  4. 4

    Associated anomalies in anophthalmia and microphthalmia.

    Stoll C, Dott B, Alembik Y, Roth MP

    European journal of medical genetics 2024; (67()):104892 doi:10.1016/j.ejmg.2023.104892.

    PMID: 38110175
  5. 5

    Management of anophthalmia, microphthalmia and coloboma in the newborn, shared care between neonatologist and ophthalmologist: a literature review.

    Russo M, Palmeri S, Zucconi A, et al.

    Italian journal of pediatrics 2025; (51(1)):65 doi:10.1186/s13052-025-01882-3.

    PMID: 40038803
  6. 6

    Large genotype-phenotype study in carriers of D4Z4 borderline alleles provides guidance for facioscapulohumeral muscular dystrophy diagnosis.

    Ricci G, Mele F, Govi M, et al.

    Scientific reports 2020; (10(1)):21648 doi:10.1038/s41598-020-78578-7.

    PMID: 33303865
  7. 7

    New insights into the phenotypic spectrum of 14q22q23 deletions: a case report and literature review.

    Pichiecchio A, Vitale G, Caporali C, et al.

    BMC medical genomics 2018; (11(1)):87 doi:10.1186/s12920-018-0405-3.

    PMID: 30268123
  8. 8

    Real-world clinical and molecular management of 50 prospective patients with microphthalmia, anophthalmia and/or ocular coloboma.

    Harding P, Gore S, Malka S, et al.

    The British journal of ophthalmology 2023; (107(12)):1925-1935 doi:10.1136/bjo-2022-321991.

    PMID: 36192130
  9. 9

    Molecular investigation in individuals with orofacial clefts and microphthalmia-anophthalmia-coloboma spectrum.

    Atique Tacla M, de Mello Copelli M, Pairet E, et al.

    European journal of human genetics : EJHG 2024; (32(10)):1257-1266 doi:10.1038/s41431-023-01488-5.

    PMID: 37932364
  10. 10

    The Developmental Landscape of Children With Uveal Coloboma and Its Relationship With Clinical Phenotype and Genetics.

    Brooks BP, Hehn AT, Blain D, et al.

    American journal of ophthalmology 2026; (282()):345-357 doi:10.1016/j.ajo.2025.11.011.

    PMID: 41248874
  11. 11

    The utility of next generation sequencing targeted multigene panels in the Adult Neurogenetic Clinic at Tygerberg Hospital, South Africa.

    Van Tonder C, Schoeman M, Carr J, et al.

    European journal of human genetics : EJHG 2025; (33(9)):1144-1152 doi:10.1038/s41431-025-01900-2.

    PMID: 40562809
  12. 12

    Identification of a novel de novo variant in OTX2 in a patient with congenital microphthalmia using targeted next-generation sequencing followed by prenatal diagnosis.

    Rafati M, Mohamadhashem F, Jalilian K, et al.

    Ophthalmic genetics 2022; (43(2)):262-267 doi:10.1080/13816810.2021.2002915.

    PMID: 34791963
  13. 13

    Abnormalities of the contralateral eye in unilateral congenital anophthalmic or blind microphthalmic patients.

    Ma L, Li Y, Zhang H, et al.

    Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus 2023; (27(1)):34.e1-34.e4 doi:10.1016/j.jaapos.2022.11.011.

    PMID: 36563895
  14. 14

    Multimodal prenatal and postnatal imaging of microphthalmia with cyst.

    Kolosky T, Uddin O, Panchal B, et al.

    Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus 2023; (27(6)):369-372 doi:10.1016/j.jaapos.2023.08.007.

    PMID: 37777051

This page provides educational information about the diagnostic workup for MAC. It does not replace professional medical advice. Always consult your pediatric ophthalmologist or medical geneticist regarding specific testing and diagnosis for your child.

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