Clinic is streamlining genetic testing and diagnoses of patients

(Image Credit: AdobeStock/Cavan)

Reviewed by Bela Parekh, BA, BS

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

This translated to proper diagnosis of challenging cases, discovery of new conditions, and contribution toward genetic research that can help larger populations. Lead author Bela Parekh, BA, BS, from 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. She has worked under the guidance of Lev Prasov, MD, PhD, at the WK Kellogg Eye Center.

Patients are referred to this clinic for inherited ocular diseases and systemic genetic disease. The most common referring diagnoses are congenital cataracts, 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 investigators noted that advances in genetic testing have improved the diagnostic capacity for genetic disorders with the scope ranging from targeted tests, ie, gene panels, to broad tests, ie, whole exome sequencing and chromosomal microarray. Moreover, balancing practical considerations of testing (financial implications, turnaround time) with diagnostic capacity continues to be a challenge.

The MOGC uses a patient-centric integrated workflow (See chart below).

MOGC study

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

The clinical and ophthalmic data that were evaluated included prenatal/birth/development histories, 3-generation pedigrees, physical examinations (ocular and systemic), ocular imaging, visual field testing, and electrophysiologic testing when indicated.

The results of the investigation showed a 76% uptake 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 were identified and are being evaluated for pathogenicity using laboratory and population studies.

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

Several case examples highlighted

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

“Completing targeted testing for patients and then broadening the testing in the event that a diagnosis is not reached allows for lower use of health care resources and a more rapid turnaround time,” the investigators concluded. “By integrating ophthalmic care with medical genetics and counseling, the MOGC solves individual patient diagnostic challenges and aids the larger population in genetic discoveries and research toward targeted therapeutics.”

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

Bela Parekh, BA, BS

E: pbela@med.umich.edu

Parekh has no financial interests related to this subject matter.