Microphthalmia, Anophthalmia, and Coloboma Genetic Epidemiology in Children (MAGIC)

The investigators are inviting families to take part in a research study that will help us better understand the physical characteristics associated with children who have Microphthalmia, Anophthalmia, and Coloboma (MAC) and how changes in their DNA sequence, called genetic mutations, play a role in the risk of developing MAC

Study Overview

• Status: Recruiting
• Conditions: Coloboma; Microphthalmia; Anophthalmia

Detailed Description

This study is focused on gathering data on individuals diagnosed with some of the more common visually threatening congenital eye defects collectively referred to as MAC complex; anophthalmia (total absence of the globe), microphthalmia (anomalously small eye in the orbit), and coloboma (failure of the closure of the fetal fissure).

Our long-term goal is to improve prevention efforts for and clinical management of MAC. The objectives of the current study are to 1) better define the MAC phenotype and 2) characterize the role of known and newly identified pathogenic genetic variants that confer MAC susceptibility.

To do this, the investigators are leveraging resources to identify MAC cases through the Texas Birth Defects Registry (TBDR), Texas Children's Hospital (TCH), and through direct referrals from our study partners. The investigators intend to conduct secondary analyses by leveraging the existing collaborative relationship with the New York State Newborn Screening Program (NYSNSP). Also, the investigators are utilizing the resources of the National Institutes of Health (NIH) Clinical Center to comprehensively phenotype cases with MAC, and the National Eye Institute (NEI) Ophthalmic Genomics Laboratory to identify genetic variants underlying MAC phenotypes.

• Study Type: Observational
• Enrollment (Estimated): 3000

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine
      • Contact: EpiCenter; Phone Number: 713-798-2920; Email: epicenter@bcm.edu
      • Principal Investigator: Philip Lupo, PhD, MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Children diagnosed with congenital microphthalmia, anophthalmia, or coloboma (without a recognized syndrome).

Description

Inclusion Criteria:

1. All MAC cases
2. Parents of the above children.
3. Siblings of the above children.
4. English or Spanish speaking.

Exclusion Criteria:

All subjects who do not meet the inclusion criteria listed above.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage 1	We are conducting interviews to collect detailed pregnancy, medical and family histories; review medical records to identify cases with chromosomal abnormalities or other syndromic diagnosis (that were not identified by the TBDR) and associated malformations, as well as to assess clinical course; and collect saliva samples that may be used to extract DNA to be analyzed for genetic mutations.	End of study, on or before 12/31/2032
Stage 2	We are also conducting in-person, virtual, or remote physical assessments to obtain detailed phenotypic information including three-dimensional (3D) digital imaging to capture facial phenotype of cases and their parents. We also collect blood samples during this stage.	End of study, on or before 12/31/2032
Stage 3	We are working closely with collaborators at the NIH Clinical Center to conduct deep phenotyping of children with MAC, who do not have a diagnosed syndrome, as well as their first-degree family members. This may include complete eye examinations, neuropsychological testing, hearing evaluation, additional facial imaging, echocardiograms, and magnetic resonance imaging (MRI) of the brain.	End of study, on or before 12/31/2032

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Collaborators: National Eye Institute (NEI); National Institutes of Health (NIH)

Publications and helpful links

General Publications

• Langlois PH, Marengo L, Lupo PJ, Drummond-Borg M, Agopian AJ, Nembhard WN, Canfield MA. Evaluating the proportion of isolated cases among a spectrum of birth defects in a population-based registry. Birth Defects Res. 2023 Jan 1;115(1):21-25. doi: 10.1002/bdr2.1990. Epub 2022 Feb 26.
• Selzer EB, Blain D, Hufnagel RB, Lupo PJ, Mitchell LE, Brooks BP. Review of evidence for environmental causes of uveal coloboma. Surv Ophthalmol. 2022 Jul-Aug;67(4):1031-1047. doi: 10.1016/j.survophthal.2021.12.008. Epub 2021 Dec 31.
• Schraw JM, Benjamin RH, Scott DA, Brooks BP, Hufnagel RB, McLean SD, Northrup H, Langlois PH, Canfield MA, Scheuerle AE, Schaaf CP, Ray JW, Chen H, Swartz MD, Mitchell LE, Agopian AJ, Lupo PJ. A Comprehensive Assessment of Co-occurring Birth Defects among Infants with Non-Syndromic Anophthalmia or Microphthalmia. Ophthalmic Epidemiol. 2021 Oct;28(5):428-435. doi: 10.1080/09286586.2020.1862244. Epub 2020 Dec 20.

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2022
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: February 21, 2024
• First Submitted That Met QC Criteria: February 27, 2024
• First Posted (Actual): March 5, 2024

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Eye Diseases, Hereditary; Congenital Abnormalities; Eye Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Coloboma; Microphthalmos; Anophthalmos
• Other Study ID Numbers: H-49046; 5U01EY032403-03 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No