Genetic Test for Hearing Loss More Sensitive, Cost-Effective than Full Work-Up
As more states require newborn hearing screening – Ohio became the 37th state to do so in 2004 – pediatricians and otolaryngologists are seeing increasing numbers of patients with hearing impairment in the first months of life. To accurately diagnose the source and extent of sensorineural hearing loss (SNHL), new research at Cincinnati Children's indicates that genetic testing provides a more sensitive and cost-effective diagnostic test than the standard comprehensive laboratory and imaging studies.
"In about half the children with SNHL, the cause is genetic. That number is increasing, thanks to earlier and better identification of hearing impairment. We are working to understand what causes hearing loss, how we can obtain the most accurate diagnosis, and how we can better tailor our treatment based on the etiology of the loss. Will a child's hearing loss get worse or stay the same? Is it associated with other medical problems? These are the questions we are studying," explains John Greinwald Jr., MD, of the Center for Hearing and Deafness Research.
Dr. Greinwald and his colleagues recently completed the first-ever study of children with idiopathic hearing loss in a consecutively enrolled SNHL cohort. They used genetic testing to determine which children in this group had connexinrelated hearing impairment. Previous studies tended to have a selection bias, Dr. Greinwald says, because they studied children in schools for the deaf and/or children with cochlear implants.
Connexin-Related Loss: 20 Percent
"We found that in any general clinic for children with hearing loss, about 20 percent will have connexin-related hearing impairment. Our findings have been corroborated by other groups. So there is good reason to subject a child to a blood test to determine if the loss is connexin-related," Dr. Greinwald explains.
Armed with genetic testing results, how can physicians make clinical predictions about a child's hearing loss? Of the 50 percent of hearing loss cases that are hereditary, 70 to 80 percent show recessive inheritance, so there are no symptoms in other family members. In addition, when children are diagnosed in the first months of life, they have no experience with speech or hearing aids. Auditory brain stem response evaluation results are helpful but not absolute.
"Our paper was the first to show genotypic and phenotypic correlations with mutations on the gene [GJB2] that causes connexin-related hearing impairment," Dr. Greinwald says. "Children with a missense mutation of the GJB2 gene, where the protein is produced but with a slight amino acid change, have a 90 percent or greater likelihood of mild to moderate hearing loss. Those with a nonsense mutation, where no protein is produced, are most likely to have severe to profound loss.
"These findings anchor GJB2 testing as a very important way to identify SNHL in children. The test gives accurate and fast information, and enables us to offer genetic counseling to families. We can predict a child's degree of hearing loss much earlier, and start planning therapy sooner."
Potential Cost Savings
Follow-up research asks, "If a physician has obtained genetic results for a child with hearing loss, why do a $2,500 workup?" Cost analysis reveals that when the first diagnostic step is GJB2 testing, medical costs can be decreased by 45 percent, due mainly to cost savings on CT scans and blood work. In addition, children and their families are spared the time and trauma of further testing. These findings support novel genetic testing early in the diagnostic process.
Developing a deafness gene chip is the next goal for Dr. Greinwald and his colleagues, with funding from Ohio's Biomedical Research and Technology Transfer Commission. The researchers hope to create novel technology that will rapidly check a much larger amount of DNA for additional genes that cause deafness.
"Early identification of SNHL is vitally important to treatment. If a mother is worried about possible hearing loss, pediatricians should order an audiogram for the child," Dr. Greinwald advises. "Once we know hearing is impaired, we have advanced molecular tools to help in treatment, prognosis and family genetic counseling. At the Center for Hearing and Deafness Research, we have a world-class interdisciplinary team of researchers, clinicians and audiologists who can help children with hearing loss and their families."
At Cincinnati Children's, Dr. Greinwald is the assistant director of the Center for Hearing and Deafness Research, assistant professor in the Division of Otolaryngology / Head and Neck Surgery, and associate director of the Hemangioma and Vascular Malformation Center. His study was published in Archives of Otolaryngology — Head & Neck Surgery (129[8]:836-840, 2003 August) and was funded by the Cincinnati Children's Research Foundation.
