Methodology of a multistate study of congenital hearing loss: Preliminary data from Utah newborn screening

Abstract

A multistate Centers for Disease Control and Prevention (CDC) study was designed to investigate the etiology of congenital hearing loss in infants ascertained through state-mandated hearing screening or early hearing loss detection and intervention (EHDI) programs. At least 50% of permanent childhood-onset hearing loss is due to genetic causes, and approximately 20% of all infants with congenital hearing loss have mutations in the GJB2 gene. Another 1% of childhood hearing loss is due to mitochondrial DNA (mtDNA) mutations. The specific aims of this study are to 1) classify the etiology of congenital hearing loss in infants by doing prospective genetic evaluations of all newborns with permanent hearing loss from defined geographic areas, 2) determine the frequency of mutations in GJB2 and two common mitochondrial mutations in these populations, and 3) establish a model infrastructure linking genetic services to statewide EHDI programs. As of April 2003, Utah is the only center evaluating patients. Study subjects identified through the Utah Department of Health EHDI program are contacted by letter and offered a comprehensive medical genetics evaluation with DNA testing for GJB2 and mitochondrial mutations A1555G and A7445G. To date, 25 probands and their immediate family members have been evaluated. We have identified 20 cases with nonsyndromic hearing loss (7 multiplex and 13 simplex), 4 with syndromic hearing loss, and 1 with presumed cytomegalovirus (CMV)-induced hearing loss. Six of 19 (32%) nonsyndromic cases with sensorineural hearing loss have mutations of one or both alleles of the GJB2 gene, and 21% are homozygous or compound heterozygotes for the 35delG mutation. No A1555G or A7445G mtDNA mutations have been found. Data reported to date include only children born in Utah, but EHDI programs in Hawaii, Rhode Island, and designated areas of Georgia have begun enrolling children in what is now a multistate collaborative study. This is the first comprehensive investigation to determine the etiology of hearing loss from populations ascertained through EHDI programs. The results of this study will facilitate the incorporation of genetic services into EHDI programs. ß

Public Attitudes Regarding the Use of Residual Newborn Screening Specimens for Research

“…2 A number of states have made these residual bloodspots available for biomedical and environmental research for a broad range of projects. [3][4][5][6] The storage and use of residual specimens for research have become controversial, primarily because of public concerns over the lack of parental awareness and consent. 7 Research demonstrates that parents are poorly informed about NBS programs in general, even when conducted with permission, and are largely unfamiliar with the practice of many health departments to retain and use residual bloodspots.…”

Rastreamento da mutação mitocondrial A1555G em pacientes com deficiência auditiva sensorioneural

“…27 The second screened 25 neonates that had altered otoacoustic emissions tests, among which the mutation was not found. 28 Screening of 300 neonates in Argentina and in 712 normal-hearing subjects did not detect the A1555G mutation. 29 These studies have reported Chart 1.…”

“…12 Although the number of cases in both groups was different from the number in some published studies, and although the mutation was not found in both groups (HLG and control groups), we were able to confirm the results of studies that also did not find the mutation in non-Asian or Arab ethnic groups. [24][25][26][27][28][29] There is a single study in Brazil reporting the findings of five families with hearing loss cases in which the prevalence of the mutation was 2% (4 cases). Only one of these positive cases was associated with an assumed aminoglycoside exposure; no mutation was found in the control group composed by black, white or Asian (Japanese or Chinese) ethnic groups.…”

Genetic testing as part of the Early Hearing Detection and Intervention (EHDI) process

“…Infants in this group need careful clinical genetic evaluations to evaluate for the possibility of a syndromic diagnosis 25 as well a follow-up studies based on the differential diagnosis outlined earlier and as recommended by the American College of Medical Genetics. 29 Current protocols suggest a workup that includes CT scanning for cochlear and vestibular anomalies, studies to determine prenatal infections such as the toxoplasmosis, rubella, cytomegalovirus, herpes virus, and syphilis, renal ultrasound, urine analysis, electrocardiogram, thyroid studies, and ophthalmological surveillance.…”

“…Knowing the GJB2/GJB6 mutation status at the outset in a child with hearing impairment will save the time, effort and cost involved with performing electrocardiograms, serial ophthalmological evaluations, renal ultrasounds, urine testing, and complicated thyroid studies. 25 Because GJB2/GJB6 genetic testing offers clinical and informational benefits, it is a near certainty that it will become an important addition to current EDHI protocols. In this commentary, we discuss issues to be considered before there is widespread inclusion of genetic testing into the EHDI process, incorporating some of our experience from our current study on the impact of genetic testing for hearing impairment on individuals and families as part of the EHDI process.…”