Testing in Infants for Prevention and Diagnosis of Hearing Loss
Background: Because hearing loss is among the most common human birth defects and because of the importance of early intervention during the early critical period for learning language (<18 months of age), states have adopted Early Detection and Hearing Intervention (EHDI) programs. Since EHDI began, more than 70 hearing impairment genes have been identified. Mutations in two of these genes, which code for proteins known as connexin 26 (GJB2 and GJB6) account for over half of the cases of genetic hearing loss in some populations. Cytomegalovirus (CMV) is another common cause of congenital (at birth) infection and a leading cause of progressive hearing loss in children in the United States. Approximately 10% to 15% of children with congenital CMV infection have some degree of hearing loss that has delayed onset and worsens during childhood.
Combining EHDI newborn hearing screening with genetic and CMV testing has the potential for rapidly diagnosing the cause and extent of hearing impairment in children.
Advances: NIDCD-supported scientists have taken the first step towards assessing the benefit of widespread inclusion of genetic testing in the EHDI process. Data suggest that children who have GJB2- related hearing impairment will benefit from cochlear implantation, so it is probable that it will become an important addition to current EHDI protocols. GJB2/GJB6 genetic testing will help to determine whether or not hearing impairment is part of a clinical syndrome, or is instead non-syndromic (not associated with any other condition) because individuals with GBJ2/GJB6-related hearing impairment do not show any other disease conditions. Once clinicians are sure that hearing impairment is non-syndromic, there is no need to continue testing for other conditions that are part of common syndromes that include hearing impairment.
In another study, NIDCD-supported investigators determined the relationship between CMV virus burden (amount of CMV DNA in the blood) and CMV related hearing loss in infancy. The amount of infectious CMV in urine and the quantity of CMV DNA in blood were determined in a group of children with congenital CMV infection and were followed for approximately 3 years. Scientists observed that a high virus burden during the first month of life is associated with hearing loss. These findings imply that it may be possible to identify children with asymptomatic CMV infection at increased risk for hearing loss by measuring virus burden during infancy.
Implications: At present, genetic testing for deafness genes is limited. However, future tests will be able to screen dozens of hearing impairment genes using complex genetic screening techniques, like microarrays. Now that GJB2/GJB6 and CMV diagnosis is theoretically achievable, scientists and policy makers should decide how best to incorporate these genetic tests into the EHDI protocol. Combining the protocols could streamline the evaluation process and avoid additional testing and recurrent evaluations.
Citations: Boppana SB, Fowler KB, Pass RF, Rivera LB, Bradford RD, Lakeman FD, Britt WJ, Congenital Cytomegalovirus Infection: Association Between Virus Burden In Infancy and Hearing Loss. J Pediatr 146: 817-823, 2005.
Schimmenti LA, Martinez A, Fox M, Crandall B, Shapiro N, Telatar M, Sininger Y, Grody WW, Palmer CG, Genetic Testing as Part of the Early Hearing Detection and Intervention (EHDI) Process. Genetics in Medicine 6: 521-525, 2004.