Early Genetic Testing Could Identify Usher Syndrome Before Visual Symptoms

Using hearing-loss gene panel testing (HLGPT), researchers found that 10% of children who have 2 specific gene variants go on to develop Usher syndrome, according to a study published in The Laryngoscope. This early genetic testing gives physicians an opportunity to identify the diagnosis at a stage prior to visual symptoms, offering the potential for “informed genetic counseling, reproductive planning, and sensory deficit interventions,” according to researchers.. 

The retrospective study looked at HLGPT, a first-line test for discovering the etiology of childhood sensorineural hearing loss in early identification of Usher syndrome before overt syndromic phenotype develops. 

“Given the progressive nature of this disease, diagnosis of syndromic features is often delayed until clinical manifestations develop. This study demonstrates how earlier diagnosis, possible through genetic testing, can aid the clinician in identifying preclinical phenotypes of Usher syndrome,” according to investigators.

They reviewed the cases of 184 children, aged 1 month to 15 years, who had next-generation sequencing of 150 genes involved in hearing loss at a tertiary pediatric children’s hospital. The sampling was ethnically and racially diverse, investigators report. About 10%, or 18 children, were found to have 2 variants in genes associated with Usher syndrome, including MYO7A, GPR98 (ADGRV1), USH2A, and PDZD7. They were referred to pediatric ophthalmology for further evaluation even though they didn’t have any known visual pathology. Of the 14 who completed a clinical ophthalmology evaluation, 29% had previously unidentified retinal abnormalities on retinal imaging or electroretinography, which was in keeping with inherited retinal degeneration.

“Hearing-loss gene panel testing of children with clinically non-syndromic sensorineural hearing loss is valuable to identify high- risk genetic variants for syndromic causes of hearing loss with age-dependent presentations, such as Usher syndrome,” researchers write. 

“This testing allows for early identification, diagnosis, and intervention on the various manifestations of the disease. In the case of Usher syndrome, where patients can develop both deafness and blindness, there is great value of early intervention to optimize these senses to limit the significant burden on communication and quality of life from the combined sensory differences.” 

The study’s limitations include its retrospective design, which limited knowledge of true prevalence, as well as factors that might prevent all parents from pursuing genetic testing for their children, including cost. In addition, 2 other patients had monoallelic heterozygous pathogenic variants on autosomal recessive genes, which were contributed to Usher syndrome, but: “the potential for the hearing loss to be attributable to other genetic causes aside from Usher syndrome is still present. Nevertheless, the presence of 2 variants in Usher genes in all of these subjects merits close ophthalmologic surveillance,” according to the research.

Reference

Brodie KD, Moore AT; Slavotinek AM, et al. Genetic testing leading to early identification of childhood ocular manifestations of usher syndrome. The Laryngoscope. Published online October 28, 2020. doi: 10.1002/lary.29193