Congenital cytomegalovirus infection

Congenital cytomegalovirus is the most common intrauterine infection and the leading non-genetic cause of sensorineural hearing loss. Worldwide, the birth prevalence is estimated at 7 per 1000 with the highest rates seen in developing countries. The highest intrauterine transmission rates and risk of neurodevelopmental sequelae are associated with primary maternal infections. Transmission occurs less frequently after non primary maternal infections due to reactivation or reinfection. 10–15% of infected infants are symptomatic at birth, with neurological symptoms present in two-thirds. Infants who are asymptomatic at birth may go on to develop late neurodevelopmental sequelae, with sensorineural hearing loss being the commonest late consequence. Prenatal, neonatal and retrospective diagnosis can be challenging. Early treatment of symptomatic neonates with the antiviral drug valganciclovir can reduce the long-term neurodevelopmental sequelae. Universal or targeted screening for congenital CMV is not currently advocated. The development of an effective vaccine appears to be some years away. This review highlights the important considerations for clinicians regarding the diagnosis, investigation and management of children with possible or confirmed congenital CMV infection.     

Multicity Italian study of congenital cytomegalovirus infection

BACKGROUND: Cytomegalovirus (CMV) infection is the most frequent congenital infection in humans. Its prevalence and the frequency of disabling sequelae must be assessed in different populations to permit the formulation or assessment of preventive measures. OBJECTIVES: To check the prevalence of congenital infection and seroprevalence in Italy; to verify the rate of sensorineural hearing loss (SNHL) in infected infants; and to assess the proportion of children with SNHL attributable to congenital CMV infection. METHODS: Diagnosis of congenital CMV infection was sought in 9032 children born between March 2002 and February 2003 by testing for viral DNA [CMV dried blood spot (DBS) test] in each newborn's Guthrie card and confirmation by isolation of CMV from urine collected in the first 3 weeks of life; CMV IgG testing in 1200 women of childbearing age; clinical and audiologic tests in the first 24 months for infected children; CMV DBS tests on the Guthrie cards collected from screening centers for 77 children (3 months-5 years) presenting SNHL of 40 dB or more. RESULTS: CMV infection was diagnosed in 14 asymptomatic and 2 symptomatic newborns (0.18%). CMV seroprevalence was 80%. In 2 infected infants, transient, unilateral SNHL was found. Nineteen of the 71 children with SNHL >70 dB were congenitally infected. CONCLUSIONS: The prevalence of congenital CMV infection is low in Italy. Population characteristics limiting the circulation of CMV strains in adult women might explain this. The fact that CMV contributes to significant SNHL highlights the need for preventive measures.     

Congenital cytomegalovirus infection

Congenital cytomegalovirus is the most common intrauterine infection and the leading non-genetic cause of sensorineural hearing loss. Worldwide, the birth prevalence is estimated at 7 per 1000 with the highest rates seen in developing countries. The highest intrauterine transmission rates and risk of neurodevelopmental sequelae are associated with primary maternal infections. Transmission occurs less frequently after non-primary maternal infections due to reactivation or reinfection. 10–15% of infected infants are symptomatic at birth with neurological symptoms present in two-thirds. Infants who are asymptomatic at birth may go on to develop late neurodevelopmental sequelae, with sensorineural hearing loss being the commonest late consequence. Prenatal, neonatal and retrospective diagnosis can be challenging. Early treatment of symptomatic neonates with the antiviral drug ganciclovir can reduce the long-term neurodevelopmental sequelae. Universal or targeted screening for congenital CMV is not currently advocated. The development of an effective vaccine appears to be some years away.     

Antiviral therapy of congenital cytomegalovirus infection

Congenital infection caused by human cytomegalovirus (CMV) is a common occurrence, but its significance is underappreciated. In the developed world, congenital CMV infection confers a tremendous medical and economic burden on society. In recent years, appreciation of the scope of disability produced by such infections in newborns, which includes neurodevelopmental sequelae and sensorineural hearing loss (SNHL), has increased. Although much of the injury produced by infection in utero likely is irreversible, antiviral therapy of newborns with CMV infection is an option available to clinicians. Currently three antivirals are licensed for treatment of CMV: ganciclovir (and its prodrug, valganciclovir), foscarnet, and cidofovir. Novel antiviral therapies, which employ mechanisms of action that differ from these agents, also are in development. Experience with these agents in the setting of congenital and perinatal CMV infection is limited, but encouraging data come from a controlled clinical trial indicating that ganciclovir therapy may be of value in limiting the neurodevelopmental injury, particularly SNHL, caused by congenital infection. Newborn screening programs for CMV infection need to be developed and implemented. Infants with congenital CMV infection, once identified, could then be considered as candidates for antiviral therapy, and careful neurodevelopmental and hearing screening follow-up care plans could be established. CMV vaccines, once available, may ultimately be the best control strategy for this important public health problem.     

Cytomegalovirus infection

Although commonly asymptomatic, congenital CMV infection is the leading cause of nonhereditary SNHL. Other sequelae that may be evident only after the neonatal period can include chorioretinitis, neurodevelopmental delay with mental or motor impairment, and microcephaly. (13) ? Congenital CMV infection is confirmed by detection of the virus in urine, blood, or saliva within the first 3 weeks of life by culture or polymerase chain reaction. A positive test does not necessarily confirm symptomatic CMV disease or need for treatment. (13) ? Postnatal CMV infections transmitted through human milk have been reported and may be clinically relevant in extremely premature infants; however, the risk-benefit ratio of pasteurizing human milk for the prevention of postnatal CMV infection is unclear. ? Ganciclovir, valganciclovir, foscarnet, cidofovir, and CMV hyperimmune globulin are effective in treating or preventing CMV infections in the immunocompromised host, but require close monitoring for associated toxicities. Treatment for congenital CMV is associated with significant toxicity and uncertain effectiveness. ? Based on strong evidence, anticipatory guidance for congenital CMV infection should include hearing tests and neurodevelopmental assessments until school age. (3) In patients with symptomatic congenital CMV infection, lifelong ophthalmologic screening should be included. (4) ? Based primarily on consensus, owing to lack of relevant clinical studies, it is not recommended to withhold human milk produced by CMV-seropositive mothers from healthy term infants. (5)(6) ? Based on some research evidence, as well as consensus, treatment for congenital CMV is recommended only in symptomatic infants with central nervous system involvement. (9)     

Congenital cytomegalovirus in Japan: More than 2 year follow up of infected newborns

Background

The aim of this study was to evaluate the outcome of congenital cytomegalovirus (CMV) infection identified on urine‐filter screening assay at >2 years’ follow up, and to observe the clinical outcomes after anti‐CMV treatment.

Methods

Sixty of 72 congenital CMV patients were enrolled and clinically observed for >2 years. Forty‐three were asymptomatic at birth; seven were symptomatic at birth but untreated with anti‐CMV drugs; and 10 were symptomatic and treated with anti‐CMV drugs.

Results

Of the 43 asymptomatic patients, three developed hearing loss or language disability for which association with congenital CMV has been repeatedly reported, and two had neurological sequelae of which the etiology was unclear, indicating that the rate of CMV‐associated late‐onset sequelae was 7–12%. All seven symptomatic infants without treatment developed sequelae, while three of the 10 treated patients were free from any sequelae.

Conclusions

The rate of late‐onset sequelae observed in Japan is similar to that reported in the USA and Europe. The treatment of symptomatic patients with antiviral agents results in favorable clinical outcomes. Thus, newborn urine–filter paper screening of congenital CMV infection is warranted.     

Congenital cytomegalovirus infection: outcome and diagnosis

Cytomegalovirus (CMV) is the most common congenital infection in humans and an important cause of morbidity and mortality in immunocompromised hosts. Congenital CMV infection occurs in approximately 0.5 to 1 percent of all newborns in the United States and can result in significant neurological sequelae. The gold standard for diagnosing congenital CMV infection is isolation of the virus from infants within the first 2 weeks of life through conventional or rapid cell culture techniques. Newer molecular diagnostic methods to diagnose congenital CMV infection, including the nucleic acid amplification of viral DNA from the peripheral blood of infants, are being investigated, and the preliminary results show promise. However, more work must be done to standardize and validate these methods before they can be used routinely in establishing the diagnosis of congenital CMV infection.     

Newborn hearing screening: will children with hearing loss caused by congenital cytomegalovirus infection be missed?

OBJECTIVE: To predict whether universal newborn auditory screening will identify most infants with sensorineural hearing loss (SNHL) caused by congenital cytomegalovirus (CMV) infection. STUDY DESIGN: A cohort of 388 children born between 1980 and 1996 at one hospital and identified during the newborn period as having congenital CMV infection received repeated hearing evaluations to assess whether hearing loss had occurred. RESULTS: SNHL was detected in 5.2% of all infants at birth. Late-onset SNHL occurred among the children throughout the first 6 years of life. By the age of 72 months, the cumulative incidence of SNHL was 15.4% in the cohort. Children with clinically apparent disease at birth had significantly more SNHL than children without any apparent disease (22.8% vs 4.0% at 3 months and 36.4% vs 11.3% at 72 months of age). CONCLUSIONS: Universal screening of hearing in neonates will detect less than half of all SNHL caused by congenital CMV infection. Because most infants with congenital CMV infection are without symptoms at birth, these children are unlikely to be recognized as being at risk for SNHL and will not receive further hearing evaluations to detect late-onset hearing loss. A combined approach of universal screening of neonates for hearing, as well as for detection of congenital CMV infection, needs to be considered.     

Evidence based management guidelines for the detection and treatment of congenital CMV

CMV is the most common congenital infection in newborns worldwide. Congenital CMV causes sensorineural hearing loss in a significant proportion of infected newborns, while the majority of newborns are asymptomatic. In the last three years there have been significant advances in the diagnosis and treatment of congenital CMV. We have developed practical evidence based guidelines for the management of congenital CMV.     

Progressive hearing loss in infants with asymptomatic congenital cytomegalovirus infection.

Congenital cytomegalovirus (CMV) infection is a major public health problem because 30,000 to 40,000 neonates with the infection are born each year in the United States. Although 90% of the congenitally infected infants are asymptomatic at birth, evidence is accumulating that these infants are at risk for audiologic, neurologic, and developmental sequelae. The current study describes the audiologic outcome of 59 infants with asymptomatic congenital CMV infection compared with 26 control infants. Eight of 59 infected infants had congenital sensorineural hearing loss (SNHL) but none of the control subjects did. Longitudinal audiologic assessments revealed that 5 of the 8 infants had further deterioration of their SNHL; a ninth infant with initially normal hearing experienced a unilateral SNHL during the first year of life, with further deterioration subsequently. The frequency of SNHL was similar for infected infants born to mothers with recurrent CMV infections during pregnancy (2 of 9) and for those born to mothers who experienced primary CMV infections (5 of 26). There was a significant difference between the occurrence of hearing loss in infected infants with normal computed tomographic scans (2 of 40) compared with those with either periventricular radiolucencies (4 of 13) or calcifications (1 of 3). Children with SNHL often have no identified cause of the loss; thus, it is likely that many of these children had asymptomatic congenital CMV infection. Given the progressive nature of SNHL associated with asymptomatic congenital CMV infection, longitudinal audiologic assessments are mandatory.     

Clinical importance of cytomegalovirus antigenemia for intrauterine cytomegalovirus infection

Background:  Little is known about the clinical importance of cytomegalovirus (CMV) antigenemia for intrauterine-CMV-infected newborns. The aims of the present study were to evaluate the diagnostic accuracy of CMV antigenemia during the neonatal period and its association with clinical manifestations.
Methods:  CMV antigenemia was analyzed using neonatal blood from 25 patients suspected of having intrauterine infection because of abnormal clinical manifestations in the mother, fetus, and newborn. Neonatal urine samples were collected for diagnosis of intrauterine infection. The diagnostic accuracy of the antigenemia analysis was evaluated by comparing it with the results of urinary CMV analyses. The clinical manifestations of antigenemia-positive and -negative infected newborns were compared in the infected newborns.
Results:  Fifteen newborns were congenitally infected and 10 were uninfected as diagnosed on virus isolation from neonatal urine. Six of 15 infected newborns were positive for CMV antigenemia. CMV antigenemia had a positive predictive value of 100%, a negative predictive value of 52.6%, a sensitivity of 40%, and a specificity of 100%. CMV retinitis and pneumonitis were more prevalent among antigenemia-positive newborns (4/6) than antigenemia-negative newborns (0/9; P  < 0.05).
Conclusions:  Antigenemia was significantly associated with retinitis and pneumonia, but it was not sensitive enough to diagnose intrauterine CMV infection.     

Clinical survey of congenital cytomegalovirus infection in Japan

Abstract Background The clinical features of congenital cytomegalovirus (CMV) infection in countries with a higher percentage of maternal seropositivity for CMV has rarely been reported. We conducted a national survey for the first time in Japan to investigate the prevalence of congenital CMV infection.
Methods: Questionnaires were sent in 1994 to pediatricians and obstetricians of 3398 hospitals with either more than 100 beds or a neonatal intensive care unit (NICU). The questionnaire asked for the number of new cases in 1992 and 1993, maternal status of CMV infection, diagnostic methods, clinical manifestations at birth, sequelae and prognosis.
Results. A total of 46 cases of CMV infection were reported for the years 1992 and 1993 by 1448 hospitals; of these 39 were symptomatic. The annual incidence of symptomatic disease was 1.6 cases/100 000 live births. Major clinical manifestations such as low birthweight, hepatosplenomegaly, petechiae and intracranial calcification were noted at birth in38–50% of symptomatic neonates. Sequelae, such as hearing loss, mental retardation and motor disability developed in 71% of survivors. Thirty-five percent of the 49 infected infants had either died or had severe disability. Several clinical manifestations at birth, including petechiae/thrombocytopenia, were significantly associated with severe sequelae or a poor prognosis.
Conclusion: The lower frequency of clinical findings at birth may be attributed to the higher seroprevalence of pregnant women in Japan than in Europe and the United States.     

CMV seroconversion in pregnants and the incidence of congenital CMV infection

In this study, it was aimed to determine the ratio of CMV seroconversion in pregnant women, the prevalence of maternal CMV infection and also the incidence of congenital CMV infection in their newborns in the Antalya region of Turkey. During a one-year period, CMV-specific IgG and IgM were determined in all (n: 1027) pregnant women admitted at 8 to 20 weeks of gestation, an according to the presence or absence of anti CMV-IgM and CMV-IgG, pregnant women were classified as seropositive, seronegative and having maternal CMV infection. Differentiation of primary and recurrent CMV infection in women with both CMV-IgM (+) and CMV-IgG (+) antibody was determined by the avidity index (AI) of anti-CMV IgG. Ultrasonographic examination was done and amniocentesis was performed at 21 to 23 weeks of gestation in pregnants with primary infection. CMV DNA was investigated in the amniotic fluid by quantitative polymerase chain reaction (qPCR). Pregnants with recurrent infection were followed only by ultrasonography for the presence of fetal abnormalities. Neonates born to mothers with CMV infection were examined for the findings of congenital CMV infection and screened for anti- CMV-IgM, CMV DNA and CMV antigenemia in the first two weeks of life. The rate of seropositivity was found as 98.5% and the rate of seronegativity as 1.5% in pregnant women. The prevalence of maternal CMV infection was found as 1.2% and among these pregnant women, the incidence of primary and recurrent maternal CMV infection was 0.3% (3 women) and 0.8% (12 women), respectively. Congenital CMV infection was detected in one of the newborns born to mothers with primary infection while no infection was detected in any of the newborns of mothers with recurrent CMV infection, so the incidence of congenital CMV infection was found as 0.1% and the rate of intrauterine infection following the primary maternal infection was 33%. In conclusion, seroprevalence rate of CMV in pregnants is high and most (66%) infections are recurrent maternal CMV infection in our region. Thus, it does not seem to be cost-effective to screen all pregnant women for CMV infection, as in the other countries with high seropositivity rate.     

Congenital cytomegalovirus infections

Congenital cytomegalovirus (CMV) infection is one of the most common viral causes of congenital infections in high resource countries and a leading cause of hearing loss as well as an important contributor to neurodevelopmental disabilities in children. During early pregnancy, CMV has a teratogenic potential and may cause malformations such as migrational disturbances in the brain, which can be visualised using neuroimaging methods such as magnetic resonance imaging (MRI) in such children. As a consequence of variation in epidemiology and seropositivity in fertile women, the prevalence of congenital CMV in their offspring varies in different countries between 0.15-2.0%. Some 10-20% of all children with congenital CMV infections exhibit signs of neurological damage when followed up. This is the case in children both with and without symptoms of infection at birth. Until vaccines and non-toxic antiviral agents are available, hygienic measures are important as prophylaxis. Treatment with antiviral agents may have a place in children with central nervous system involvement during the neonatal period.     

Coste efectividad de la estrategia de cribado de citomegalovirus en recién nacidos mayores de 34 semanas de bajo peso para la edad gestacional

IntroductionInfection by cytomegalovirus (CMV) is one of the most common congenital infections, with a global prevalence of 0.3%-2.4%. In Spain, CMV screening is not performed during pregnancy, but rather in neonates with risk factors, and, in many hospitals, in those born small for gestational age (SGA). Screening is usually performed by measurement of the viral load in urine by polymerase chain reaction (PCR) and/or head ultrasound in search of compatible features.The aim of the study was to assess the yield of the CMV PCR test in urine and head ultrasound examination in asymptomatic neonates born SGA after 34 weeks’ gestation. The secondary objective was to assess the cost-effectiveness of this strategy.Design and methodsWe conducted an observational and retrospective study between January and December 2019 in a tertiary care hospital. It included neonates delivered after 34 weeks, SGA and without additional risk factors assessed with a CMV PCR test in urine and/or head ultrasound.ResultsThe sample included 259 patients. It was divided in two groups: group 1, patients with a head circumference, weight and length below the 10th percentile (53 patients; 20.5%), and group 2, patients in whom only the weight was below the 10th percentile (206 patients; 79.5%). The incidence of late preterm birth, twin pregnancy, neonatal admission and exposure to illicit drugs during gestation was higher in group 1. A total of 186 urine PCR tests and 223 head ultrasounds were performed overall, and both tests were performed more frequently in group 1 (P=.002). There was only one positive CMV PCR test result in the sample (0.54%), corresponding to a patient in group 2 with no abnormal sonographic findings who remained asymptomatic throughout the followup. Two head ultrasound examinations yielded abnormal findings, in both cases unrelated to congenital CMV infection. We performed a cost-effectiveness analysis and determined that the cumulative cost of head ultrasound examinations and urine CMV PCR tests in our sample amounted to €17 000 for the detection of a single asymptomatic positive case.ConclusionIn our population, screening for congenital CMV infection in asymptomatic late preterm and term newborns whose only risk factor is SGA does not seem to be cost effective. It would be necessary to expand the sample to other populations.     

Congenital cytomegalovirus infection - a common cause of hearing loss of unknown aetiology

Aim: The aim of this study was to investigate the role of congenital cytomegalovirus (CMV) infection as a cause of various types of sensorineural hearing loss (SNHL) in a group of nonsyndromic children with otherwise unknown aetiology of hearing loss. Furthermore, the occurrence of combined congenital CMV infection and connexin 26 (Cx26) mutations was investigated. Methods: The dried blood spot (DBS) cards of 45 children with various degrees of hearing deficits and 46 children with severe/profound hearing loss were tested for CMV DNA with polymerase chain reaction (PCR) technique. The DBS cards of the 46 children with severe/profound hearing loss were also analysed for Cx26 mutations. Results: Of the 45 children with various degrees of hearing loss, nine were positive for CMV DNA (20%). The nine children represented severe/profound, mild and unilateral hearing loss. From the 46 children with severe/profound hearing loss, nine of 46 (20%) were positive for CMV DNA. In addition, three of the CMV DNA‐positive children were carriers of mutations of Cx26. Conclusion: Congenital CMV infection is a high risk factor in hearing impairment among children.     

Utilisation des tests virologiques pour le diagnostic,le pronostic et la surveillance des infections congénitales à cytomégalovirus

Cytomegalovirus (CMV) infection is the main cause of congenital infection in industrialized countries. The virological tools used for the diagnosis of congenital CMV are serology for diagnosis of primary infection in the mother, CMV PCR in amniotic fluid for diagnosis of fetal infection, PCR in urine or saliva for neonatal diagnosis and PCR in dried blood spots on Guthrie cards for retrospective diagnosis in young children. The prognostic value of viral load in amniotic fluid, fetal blood and neonatal blood will be discussed. The performance of the virological tests for antenatal or postnatal screening of congenital CMV will also be discussed.     

Prevalence and clinical aspects of congenital cytomegalovirus infection

OBJECTIVES: The objectives of the present study were to determine the prevalence of congenital CMV infection, as well as to evaluate the importance of this agent as cause of congenital disease, and to describe the clinical manifestations in children attended at a General Hospital in Ribeir?o Preto, SP, Brazil. POPULATION AND METHODS: A first group including 189 newborns and their mothers was evaluated for the prevalence of the congenital CMV infection. A second group including 130 newborns and 74 infants who presented clinical manifestations of congenital disease were also investigated to evaluate the importance of the CMV as a cause of this disease and to describe the clinical findings. Diagnosis of congenital CMV infection was established by detecting the virus using viral isolation in tissue culture, polymerase chain reaction DNA amplification in urine samples and detection of specific anti-CMV IgM and IgG by immunofluorescence indirect test. RESULTS: The prevalence of congenital CMV infection was 2.6% and the prevalence of CMV antibodies in mothers was 95%. In the first group, none of the 5 congenitally infected presented clinical apparent disease at birth, although one of them had intracranial calcifications. In the second group, CMV was recognized as a causative of congenital disease in 12 children (5.9%). Of these, 10(83%) were identified after the neonatal period. The clinical findings included hepatosplenomegaly (75%), jaundice with direct hyperbilirubinemia (42%), neurologic disease consisting of microcephaly and intracranial calcifications in 42% of these children. CONCLUSIONS: The prevalence of congenital CMV infection was similar to that reported in other studies about highly immune populations. Infants with asymptomatic congenital CMV infection may have diseases of the central nervous system that are not clinically evident at birth, such as punctate calcifications. CMV infected patients who are symptomatic at birth have a multisystem disease, and the differential diagnosis of any newborn with clinical abnormalities including involvement of the hepatobiliary, hematopoietic and central nervous systems should include congenital CMV infection. CMV was an important agent of these abnormalities, and the majority of symptomatic patients were identified after the neonatal period, making the diagnosis more difficult.     

Urine polymerase chain reaction as a screening tool for the detection of congenital cytomegalovirus infection

OBJECTIVES: To define the incidence of congenital cytomegalovirus (CMV) infection in a defined population in Israel as diagnosed by urine polymerase chain reaction (PCR), and to assess the utility of this method for screening for congenital CMV infection. DESIGN: A convenient sample of urine specimens from asymptomatic newborns were subjected to CMV PCR. Positive results were validated by urine tube culture and by determination of serum CMV IgM antibodies. Maternal CMV IgG was determined in a representative sample of mothers. Newborns with positive urine specimens underwent full clinical evaluation. Epidemiological characteristics of the mothers were extracted from the medical records. SETTINGS: Two medical centres in Israel with different population characteristics. PATIENTS: A total of 2000 newborns (1000 in each medical centre). MAIN OUTCOME MEASURE: Presence of CMV DNA in the urine. RESULTS: Despite significant epidemiological differences between the populations in the two hospitals, the CMV seroprevalence was similar, 80.5% and 85%. Fourteen of the 2000 newborns screened (0.7%) were PCR positive. Urine culture was positive in nine of 10 specimens; IgM was positive in only two of 13 newborns with positive PCR. Eleven newborns underwent full or partial evaluation, and only one (9%) was symptomatic. CONCLUSIONS: The incidence of congenital CMV infection in the study population was 0.7%; over 90% were asymptomatic. Urinary CMV PCR is a reliable, rapid, and convenient method, and thus may serve as a screening tool for the detection of congenital CMV infection.     

GJB2 and GJB6 mutations in children with congenital cytomegalovirus infection

Congenital cytomegalovirus (CMV) infection is a leading cause of sensorineural hearing loss (SNHL) in children. Whether connexin mutations are factors in the development of CMV-related hearing loss has not been explored. We examined gap junction protein beta-2 (GJB2) and gap junction protein beta-6 (GJB6) mutations in 149 children with congenital CMV infection and 380 uninfected neonates. Mutations in GJB2 and GJB6 were assessed by nucleotide sequencing and polymerase chain reaction (PCR) methods, respectively. The study population was predominantly African American, and 4.3% of the subjects were carriers of a connexin 26 mutation. The overall frequency of GJB2 mutations was significantly higher in the group of children with CMV infection and hearing loss (21%) compared with those with CMV infection and normal hearing (3%, p = 0.017) and the group of uninfected newborns (3.9%, p = 0.016). Eight previously reported mutations (M34T, V27I, R127H, F83L, R143W, V37I, V84L, G160S), and four novel mutations (V167M, G4D, A40T, and R160Q) were detected. None of the study children had the 342-kb deletion (delGJB6-D13S1830) in GJB6, which suggests that this mutation does not play a role in hereditary deafness in the African American population. Although GJB2 mutations were detected in children with and without CMV-related hearing loss, those with hearing loss had a higher frequency of GJB2 mutations.