The clinic is streamlining genetic testing and patient diagnoses

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Reviewed by Bela Parekh, BA, BS

Experience with a new multidisciplinary ophthalmic genetics clinic (MOGC) at the Kellogg Eye Center, University of Michigan, Ann Arbor indicated that this integrated approach has led to the identification of a wide variety of inherited diseases and provided insight genetic diagnosis for many diagnostic odysseys . These include genetic disorders with eye involvement as well as patients with eye disorders that can be part of multisystem syndromes.

This has translated into correctly diagnosing difficult cases, discovering new conditions, and contributing to genetic research that can help larger populations. Lead author Bela Parekh, BA, BS, of the University of Michigan Medical School, Department of Ophthalmology and Visual Sciences, reported the team’s findings at the Real World Ophthalmology conference in Chicago, Illinois. You worked under the guidance of Lev Prasov, MD, PhD, at the WK Kellogg Eye Center.

Patients are referred to this clinic for hereditary eye diseases and systemic genetic diseases. The most common referral diagnoses are congenital cataract, microphthalmia/anophthalmia/coloboma spectrum disorders, anterior segment dysgenesis, optic nerve atrophy, nystagmus, and other anomalies.

The MOGC team includes an ophthalmic geneticist, a medical geneticist and a genetic counselor. The researchers noted that advances in genetic testing have improved diagnostic ability for genetic disorders ranging in scope from targeted testing, ie gene panels, to broad testing, ie whole exome sequencing and chromosome microarray. Additionally, balancing the practical considerations of testing (financial implications, lead times) with diagnostic capability continues to be a challenge.

The MOGC uses an integrated patient-centric workflow (see graphic below).

MOGC study

This was a cohort study using data from the retrospective chart review of 71 patients seen at the Kelloggs MOGC from July 2020 to October 2022.

Clinical and ophthalmic data that were evaluated included prenatal/birth/developmental histories, 3-generation pedigree, physical exams (ocular and systemic), ocular imaging, visual field tests, and electrophysiological tests when indicated.

Survey results showed uptake of 76% for genetic testing and diagnostic yield in 33% of cases based on the patient-specific strategy provided by the MOGC. Additional cases with variants of unknown significance have been identified and are being evaluated for pathogenicity by laboratory and population studies.

The reasons patients gave for not undergoing genetic testing were personal, financial and logistical, including the inability to return a DNA test kit.

Several examples of highlighted cases

The first case was that of an 11-year-old boy with syndromic optic neuropathy. He had a history of visual impairment, nystagmus, esotropia with abduction deficiency, developmental delay, seizures, and dysmorphic seizures. Whole exome testing showed a de novo pathogenic variant in NR2F1, which confirmed Bosch-Boonstra-Schaaf optic atrophy syndrome and concluded a long diagnostic journey for the patient whose symptoms, until then, were seemingly unrelated.

A second case was familial anterior segment dysgenesis in a 5-month-old patient who presented with bilateral absent red reflexes and corneal opacification. She was later diagnosed with microphthalmia, bilateral partial aniridia, and congenital glaucoma. She had a family history suggestive given the clinical findings in the mildly affected mother. FOXC1-related anterior segment dysgenesis syndrome with a maternally inherited pathogenic variant was confirmed through panel-based genetic testing. The clinical diagnosis was Axenfeld-Rieger syndrome.

Completing targeted testing for patients and then scaling up testing in case a diagnosis is not reached allows for lower utilization of healthcare resources and faster response times, the researchers concluded. By integrating ophthalmic care with medical genetics and counseling, the MOGC solves individual patient diagnostic challenges and assists the wider population in genetic discoveries and research toward targeted therapies.

For more information or to refer patients to the MOGC, call 734-764-4190.

Bela Parekh, BA, BS
Parekh has no financial interests related to this matter.

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