Defining Collective Priorities: Research and Learning Agendas for Family Planning Across 6 Countries.

Evidence should be the foundation for a well-designed family planning (FP) program, but existing evidence is rarely aligned with and/or synthesized to speak directly to FP programmatic needs. Based on our experience cocreating FP research and learning agendas (FP RLAs) in Côte d'Ivoire, Malawi, Mozambique, Nepal, Niger, and Uganda, we argue that FP RLAs can drive the production of coordinated research that aligns with national priorities.To cocreate FP RLAs, stakeholders across 6 countries conducted desk reviews of 349 documents and 106 key informant interviews, organized consultation meetings in each country to prioritize evidence gaps and generate research and learning questions, and, ultimately, formed 6 FP RLAs comprising 190 unique questions. We outline the process for consensus-driven development of FP RLAs and communicate the results of an analysis of the questions in each FP RLA across 4 technical areas: self-care, equity, high impact practices, and youth. Each question was categorized as a learning versus research question, the former indicating an opportunity to synthesize existing evidence and the latter to conduct new research to answer the question. Themes emerging from the data shed light on shared evidence gaps across the 6 countries. We argue that similarities and differences in the questions in each FP RLA reflect the unique implementation experience and context, as well as each country's placement on the FP S-curve. Early uses of the FP RLAs include informing the development of FP costed implementation plans and FP2030 commitments. FP RLAs have also been discussed in multiple thematic working groups. For FP stakeholders, these FP RLAs represent a consensus-based agenda that can guide the generation and synthesis of evidence to answer each country's most pressing questions, ultimately driving progress toward increasingly evidence-based programming and policy.

Adapting High Impact Practices in Family Planning During the COVID-19 Pandemic: Experiences From Kenya, Nigeria, and Zimbabwe.

BACKGROUND: We describe how High Impact Practices (HIPs) in family planning (FP) were adapted across Kenya, Nigeria, and Zimbabwe to maintain access to services in response to the coronavirus disease (COVID-19) pandemic. METHODS: Using a qualitative data collection tool structured around 3 HIP categories (service delivery, demand creation, and enabling environment), adaptations in FP programs during the pandemic were documented. We describe adaptations made to 3 specific HIPs: mobile outreach, community health workers, and digital health for social and behavior change. PROGRAM EXPERIENCES: In Zimbabwe, the Mhuri/Imuli project adapted its mobile outreach model integrating community-based outreach with facility-based outreach. The number of outreach clients served per week peaked at 1,759 (July 2020) from a low of 203 (May 2020). Clients choosing long-acting reversible methods increased from 22% to 59% during the 3 months before and after lockdown, respectively.In Kenya, a program addressed youth's hesitation to visit health facilities through youth community health volunteers, who provided counseling, community dialogues, contraceptive pills, and condoms. Over 6 months, the program reached 1,048 youth with community dialogues, and 4,656 youth received FP services. In Nigeria, peer mobilizers provided services through a socially distanced community-based program to help adolescent girls access contraceptive self-injection when movement restrictions limited youth's ability to travel to facilities.In Nigeria, Adolescents 360 adapted sexual and reproductive health information programs for virtual delivery through WhatsApp. A contraceptive education Facebook campaign gained more than 80,000 followers, reached 5.9 million adolescents, and linked 330 adolescents to program-supported facilities from January to March 2021. In Kenya, the Kibera-based project used WhatsApp to reach youth with discussion groups and health workers with skills strengthening. CONCLUSION: Monitoring how projects adapt HIPs to ensure continuity of care during the COVID-19 pandemic can help inform the implementation of successful adaptations in the face of present and future challenges.

Integrated delivery of family planning and childhood immunization services: a qualitative study of factors influencing service responsiveness in Malawi.

Evidence from several countries in sub-Saharan Africa suggests that the integration of family planning (FP) with childhood immunization services can help reduce the unmet need for FP among postpartum women without undermining the uptake of immunizations. However, the quality and responsiveness of FP services that are integrated with childhood immunizations remain understudied. A qualitative study was conducted in two districts of Malawi, which examined the factors influencing the responsiveness of FP services that were integrated with childhood immunizations in monthly public outreach clinics. Semi-structured interviews with clients (n = 23) and FP providers (n = 10) and a clinic audit were carried out in six clinics. Hardware (material) and software (relational) factors influencing service responsiveness were identified through thematic and framework analyses of interview transcripts, and clinic characteristics were summarized from the audit data to contextualize the qualitative findings. Overall, 13 factors were found to influence service responsiveness in terms of the ease of access, choice of provider, environment, service continuity, confidentiality, communication, dignity and FP counselling afforded to clients. Among these factors, hardware deficiencies, including the absence of a dedicated building for the provision of FP services and the lack of FP commodities in clinics, were perceived to negatively affect service responsiveness. Crucially, the providers' use of their agency to alter the delivery of services was found to mitigate the negative effects of some hardware deficits on the ease of access, choice of provider, environment and confidentiality experienced by clients. This study contributes to an emerging recognition that providers can offset the effect of hardware deficiencies when services are integrated if they are afforded sufficient flexibility to make independent decisions. Consideration of software elements in the design and delivery of FP services that are integrated with childhood immunizations is therefore critical to optimize the responsiveness of these services.

"It was my own decision": the transformational shift that influences a woman's decision to use contraceptives covertly.

BACKGROUND: Family planning (FP) is an important element of sexual and reproductive health and rights, but socio-cultural barriers and unbalanced gender relations often limit women's decision-making about contraceptive use. Covert contraceptive use (CCU) exemplifies the limits on women's decision-making and represents a way in which some women overcome constraints to achieve their reproductive goals. This study explores the decision-making process through which women choose to use contraceptives covertly. METHODS: A qualitative synthesis was conducted using data from women, health providers, community members, health administrators, and intervention implementers (n = 400) to explore the decision-making process through which women choose to use contraceptives covertly. Interviews and focus group discussions were conducted at two time points as part of an evaluation of interventions integrating FP and childhood immunisation services at sites in Benin, Kenya, Malawi and Uganda. The sexual and reproductive health empowerment framework by Karp et al. (2020) was adapted and used to guide the analysis. RESULTS: Women recognised that although they suffered the negative consequences of frequent pregnancies and of raising large families, they lacked overt decision-making power over their fertility. Women were confident to engage in CCU because they believed their husbands did not understand these consequences nor acknowledged their suffering, which justified not informing them. CCU was a difficult choice however, women felt comfortable voicing their reproductive preferences in settings where health providers were supportive. CONCLUSIONS: Women chose to use contraceptives covertly when they questioned the unfairness of their situation and recognised their own power to act in accordance with their reproductive preferences. This represented an important shift in a woman's perception of who is entitled to make decisions about contraceptive use. Importantly, health providers can play a key role in supporting women's autonomous decision making about contraceptive use and should be careful not to undermine women's confidence.

Integrated delivery of family planning and childhood immunisation services: a mixed methods assessment of service responsiveness.

BACKGROUND: Postpartum women represent a considerable share of the global unmet need for modern contraceptives. Evidence suggests that the integration of family planning (FP) with childhood immunisation services could help reduce this unmet need by providing repeat opportunities for timely contact with FP services. However, little is known about the clients' experiences of FP services that are integrated with childhood immunisations, despite being crucial to contraceptive uptake and repeat service utilisation. METHODS: The responsiveness of FP services that were integrated with childhood immunisations in Malawi was assessed using cross-sectional convergent mixed methods. Exit interviews with clients (n=146) and audits (n=15) were conducted in routine outreach clinics. Responsiveness scores across eight domains were determined according to the proportion of clients who rated each domain positively. Text summary analyses of qualitative data from cognitive interviewing probes were also conducted to explain responsiveness scores. Additionally, Spearman rank correlation and Pearson's chi-squared test were used to identify correlations between domain ratings and to examine associations between domain ratings and client, service and clinic characteristics. RESULTS: Responsiveness scores varied across domains: dignity (97.9%); service continuity (90.9%); communication (88.7%); ease of access (77.2%); counselling (66.4%); confidentiality (62.0%); environment (53.9%) and choice of provider (28.4%). Despite some low performing domains, 98.6% of clients said they would recommend the clinic to a friend or family member interested in FP. The choice of provider, communication, confidentiality and counselling ratings were positively associated with clients' exclusive use of one clinic for FP services. Also, the organisation of services in the clinics and the providers' individual behaviours were found to be critical to service responsiveness. CONCLUSIONS: This study establishes that in routine outreach clinics, FP services can be responsive when integrated with childhood immunisations, particularly in terms of the dignity and service continuity afforded to clients, though less so in terms of the choice of provider, environment, and confidentiality experienced. Additionally, it demonstrates the value of combining cognitive interviewing techniques with Likert questions to assess service responsiveness.

Improving provision of family planning among pastoralists in Kenya: Perspectives from health care providers, community and religious leaders.

There exist significant inequities in access to family planning (FP) in Kenya, particularly for nomadic and semi-nomadic pastoralists. Health care providers (HCP), are key in delivering FP services. Community leaders and religious leaders are also key influencers in women's decisions to use FP. We found limited research exploring the perspectives of both HCPs and these local leaders in this context. We conducted semi-structured interviews with HCPs (n=4) working in facilities in Wajir and Mandera, and community leaders (n=4) and religious leaders (n=4) from the nomadic and semi-nomadic populations the facilities serve. We conducted deductive and inductive thematic analysis. Three overarching themes emerged: perception of FP as a health priority, explanations for low FP use, and recommendations to improve access. Four overlapping sub-themes explained low FP use: desire for large families, tension in FP decision-making, religion and culture, and fears about FP. Providers were from different socio-demographic backgrounds to the communities they served, who faced structural marginalisation from health and other services. Programmes to improve FP access should be delivered alongside interventions targeting the immediate health concerns of pastoralist communities, incorporating structural changes. HCPs that are aware of religious and cultural reasons for non-use, play a key role in improving access.

"As a woman who watches how my family is I take the difficult decisions": a qualitative study on integrated family planning and childhood immunisation services in five African countries.

BACKGROUND: Family planning (FP) has the potential to improve maternal and child health outcomes and to reduce poverty in sub-Saharan Africa. However, substantial unmet need for modern contraceptive methods (MCMs) persists in this region. Current literature highlights multi-level barriers, including socio-cultural norms that discourage the use of MCMs. This paper explores women's choices and decision-making around MCM use and examines whether integrating FP services with childhood immunisations influenced women's perceptions of, and decision to use, an MCM. METHODS: 94 semi-structured interviews and 21 focus group discussions with women, health providers, and community members (N = 253) were conducted in health facilities and outreach clinics where an intervention was delivering integrated FP and childhood immunisation services in Benin, Ethiopia, Kenya, Malawi and Uganda. Data were coded using Nvivo software and an analytical framework was developed to support interpretative and thematic analyses on women's decision-making about MCM use. RESULTS: Most women shared the reproductive desire to space or limit births because of the perceived benefits of improved health and welfare for themselves and for their children, including the economic advantages. For some, choices about MCM use were restricted because of wider societal influences. Women's decision to use MCMs was driven by their reproductive desires, but for some that was stymied by fears of side effects, community stigma, and disapproving husbands, which led to clandestine MCM use. Health providers acknowledged that women understood the benefits of using MCMs, but highlighted that the wider socio-cultural norms of their community often contributed to a reluctance to use them. Integration of FP and childhood immunisation services provided repeat opportunities for health providers to counter misinformation and it improved access to MCMs, including for women who needed to use them covertly. CONCLUSIONS: Some women chose to use MCMs without the approval of their husbands, and/or despite cultural norms, because of the perceived health and economic benefits for themselves and for their families, and because they lived with the consequences of short birth intervals and large families. Integrated FP and childhood immunisation services expanded women's choices about MCM use and created opportunities for women to make decisions autonomously.

Context-acceptability theories: example of family planning interventions in five African countries.

BACKGROUND: Family planning (FP) can lengthen birth intervals and potentially reduce the risk of foetal death, low birthweight, prematurity, and being small for gestational age. Effective FP is most easily achieved through access to and acceptability of modern contraceptive methods (MCMs). This study aimed to identify mechanisms of acceptability and the contexts in which they are triggered and to generate theories to improve the selection and implementation of effective interventions by studying an intervention integrating FP with childhood immunisation services. METHODS: Qualitative interpretative synthesis of findings from realist evaluations of FP interventions in five African countries was guided by an analytical framework. Empirical mechanisms of acceptability were identified from semi-structured interviews and focus group discussions with key stakeholders (N = 253). The context in which these mechanisms were triggered was also defined. Empirical mechanisms of acceptability were matched to constructs of a theoretical framework of acceptability. Context-acceptability theories (CATs) were developed, which summarised constructs of acceptability triggered for specific actors in specified contexts. Examples of interventions that may be used to trigger acceptability for these actors were described. RESULTS: Seven CATs were developed for contexts with strong beliefs in religious values and with powerful religious leaders, a traditional desire for large families, stigmatisation of MCM use, male partners who are non-accepting of FP, and rumours or experiences of MCM side effects. Acceptability mechanisms included alignment with values and beliefs without requiring compromise, actors' certainty about their ability to avoid harm and make the intervention work, and understanding the intervention and how it works. Additionally, acceptability by one group of actors was found to alter the context, triggering acceptability mechanisms amongst others. CONCLUSIONS: This study demonstrated the value of embedding realist approaches within implementation research. CATs are transferable theories that answer the question: given the context, what construct of acceptability does an intervention need to trigger, or more simply, what intervention do we need to apply here to achieve our outcomes? CATs facilitate transfer of interventions across geographies within defined contexts.

Integrated delivery of family planning and childhood immunisation services in routine outreach clinics: findings from a realist evaluation in Malawi.

BACKGROUND: Family planning (FP) needs among postpartum women in low- and middle-income countries remain largely unmet. Integrating FP with childhood immunisation services could partially reduce this unmet need by creating multiple opportunities for timely contact with FP services during the 12 months following childbirth. METHODS: A realist evaluation of an intervention integrating FP and childhood immunisation services in routine outreach clinics in two rural districts of Malawi was conducted. A Context-Mechanism-Outcome (CMO) framework was used to describe the drivers of the intervention. A detailed programme theory was developed based on the analysis of semi-structured interviews and focus group discussions with 50 stakeholders. RESULTS: A total of 9 core mechanisms were identified, which centred on constructs of access. Findings revealed that on the demand side, women were motivated to attend outreach clinics due to shorter travel distances; they felt confident they could access FP services and use contraceptive methods covertly if needed; and when supported by their husband, they were empowered to take up the use of contraceptive methods. On the supply side, providers were empowered through the training they received to provide integrated services; they were confident in their ability to provide essential services; and they were motivated by teamwork and by the recognition they received for their work. Additionally, some providers were found to be unwilling to walk long distances to reach remote clinics, which was seen to negatively affect the availability of services. CONCLUSIONS: The delivery of integrated FP and childhood immunisation services in the context of routine outreach clinics in rural Malawi was seen to trigger mechanisms of accessibility and to improve the acceptability and availability of FP services. However, further research is needed to understand how the integration of these services in a routine outreach clinic setting may affect other dimensions of accessibility, including the approachability, appropriateness and affordability of services.

Use of SLC26A4 mutation testing for unilateral enlargement of the vestibular aqueduct.

IMPORTANCE: Approximately one-half of all subjects with unilateral or bilateral hearing loss with enlargement of the vestibular aqueduct (EVA) will have SLC26A4 gene mutations. The number (0, 1, or 2) of mutant alleles of SLC26A4 detected in an individual subject with EVA is each associated with a distinct combination of diagnostic and prognostic information as well as probability of recurrence of EVA in siblings. OBJECTIVE: To evaluate the results of SLC26A4 mutation testing in subjects with unilateral EVA. (The study objective was formulated before data were collected.) DESIGN: Prospective cross-sectional study of cohort ascertained between 1998 and 2012. SETTING: National Institutes of Health Clinical Center, a federal biomedical research facility. PARTICIPANTS: Twenty-four subjects (10 males, 14 females) with unilateral EVA, defined as a midpoint diameter greater than 1.5 mm, who were referred or self-referred to participate in a study about the clinical and molecular analysis of EVA. Twenty-one (87.5%) of 24 subjects were white. Mean age was 10.3 years (age range, 5-39 years). INTERVENTION: SLC26A4 mutation analysis. MAIN OUTCOMES AND MEASURES: Audiometric results, the presence or absence of EVA, and the number of mutant alleles of SLC26A4. RESULTS: Approximately 8.3% of the subjects with unilateral EVA had 2 mutant SLC26A4 alleles, 16.7% had 1 mutant allele, and 75.0% had 0 mutant alleles. CONCLUSIONS AND RELEVANCE: Unilateral EVA can be associated with all possible SLC26A4 genotype results. The distinct combination of prognoses and recurrence probability associated with each genotype supports the clinical use of testing for SLC26A4 mutations in subjects with unilateral EVA.

Promoting healthy timing and spacing of pregnancy with young married women in Northern Nigeria: a short report.

The persistence of early and closely spaced pregnancies in Northern Nigeria contributes to maternal and child morbidity and mortality. A technical working group to WHO recommended that following a birth, a woman should space her next pregnancy by at least 24 months, and following a miscarriage or abortion, a woman space her next pregnancy by at least six months. UNICEF, UNFPA and WHO also recommend that a woman delay her first pregnancy until 18. These recommendations comprise the concept of Healthy Timing and Spacing of Pregnancy. The Extending Service Delivery Project (ESD) partnered with the Federation of Muslim Women Association of Nigeria and religious leaders to educate communities about the benefits of using family planning to practice HTSP in five local government areas. Informal discussions with 148 women and 28 men found high recall of the HTSP recommendations and favorable attitudes toward spacing and family planning although many remain concerned about the side effects of contraceptive methods.

Commentary on "Otolaryngology-head and neck surgery physician workforce issues an analysis for future specialty planning" by Kim, Cooper, and Kennedy.

An impending physician shortage has been projected. The article by Kim, Cooper, and Kennedy, titled "Otolaryngology-Head and Neck Surgery Physician Workforce Issues: An Analysis for Future Specialty Planning," is an attempt to evaluate and address this potential shortage as it applies to otolaryngology. The authors of this comment have concerns about the article's assumptions, design, and recommendations. Kim et al attempt to extrapolate data from other specialties and other countries to the US otolaryngology workforce, use that data in modeling methods without demonstrated validity, and based on their analysis, they recommend drastic changes to otolaryngologic training and practice in the United States. Particularly troublesome are (1) the emphasis placed on gender and part-time work and (2) the measurement of productivity defined as hours worked per week. Before redefining our specialty, more thorough and systematic data acquisition and review are necessary to meet the needs of our patients now and in the future.

SLC26A4 genotype, but not cochlear radiologic structure, is correlated with hearing loss in ears with an enlarged vestibular aqueduct.

OBJECTIVES/HYPOTHESIS: Identify correlations among SLC26A4 genotype, cochlear structural anomalies, and hearing loss associated with enlargement of the vestibular aqueduct (EVA). STUDY DESIGN: Prospective cohort survey, National Institutes of Health, Clinical Center, a federal biomedical research facility. METHODS: Eighty-three individuals, 11 months to 59 years of age, with EVA in at least one ear were studied. Correlations among pure-tone hearing thresholds, number of mutant SLC26A4 alleles, and the presence of cochlear anomalies detected by computed tomography or magnetic resonance imaging were examined. RESULTS: Linear mixed-effects model indicated significantly poorer hearing in ears with EVA in individuals with two mutant alleles of SLC26A4 than in those with EVA and a single mutant allele (P = .012) or no mutant alleles (P = .007) in this gene. There was no detectable relationship between degree of hearing loss and the presence of structural cochlear anomalies. CONCLUSIONS: The number of mutant alleles of SLC26A4, but not the presence of cochlear anomalies, has a significant association with severity of hearing loss in ears with EVA. This information will be useful for prognostic counseling of patients and families with EVA.

Evaluation of the thyroid in patients with hearing loss and enlarged vestibular aqueducts.

OBJECTIVE: To evaluate thyroid structure and function in patients with enlargement of the vestibular aqueduct (EVA) and sensorineural hearing loss. DESIGN: Prospective cohort survey. SETTING: National Institutes of Health Clinical Center, a federal biomedical research facility. PATIENTS: The study population comprised 80 individuals, aged 1.5 to 59 years, ascertained on the basis of EVA and sensorineural hearing loss. MAIN OUTCOME MEASURES: Associations among the number of mutant alleles of SLC26A4; volume and texture of the thyroid; percentage of iodine 123 ((123)I) discharged at 120 minutes after administration of perchlorate in the perchlorate discharge test; and peripheral venous blood levels of thyrotropin, thyroxine, free thyroxine, triiodothyronine, thyroglobulin, antithyroid peroxidase and antithyroglobulin antibodies, and thyroid-binding globulin. RESULTS: Thyroid volume is primarily genotype dependent in pediatric patients but age dependent in older patients. Individuals with 2 mutant SLC26A4 alleles discharged a significantly (P < or = .001) greater percentage of (123)I compared with those with no mutant alleles or 1 mutant allele. Thyroid function, as measured by serologic testing, is not associated with the number of mutant alleles. CONCLUSIONS: Ultrasonography with measurement of gland volume is recommended for initial assessment and follow-up surveillance of the thyroid in patients with EVA. Perchlorate discharge testing is recommended for the diagnostic evaluation of patients with EVA along with goiter, nondiagnostic SLC26A4 genotypes (zero or 1 mutant allele), or both.

Hypo-functional SLC26A4 variants associated with nonsyndromic hearing loss and enlargement of the vestibular aqueduct: genotype-phenotype correlation or coincidental polymorphisms?

Hearing loss with enlargement of the vestibular aqueduct (EVA) can be associated with mutations of the SLC26A4 gene encoding pendrin, a transmembrane Cl(-)/I(-)/HCO(3)(-) exchanger. Pendrin's critical transport substrates are thought to be I(-) in the thyroid gland and HCO(3)(-) in the inner ear. We previously reported that bi-allelic SLC26A4 mutations are associated with Pendred syndromic EVA whereas one or zero mutant alleles are associated with nonsyndromic EVA. One study proposed a correlation of nonsyndromic EVA with SLC26A4 alleles encoding pendrin with residual transport activity. Here we describe the phenotypes and SLC26A4 genotypes of 47 EVA patients ascertained since our first report of 39 patients. We sought to determine the pathogenic potential of each variant in our full cohort of 86 patients. We evaluated the trafficking of 11 missense pendrin products expressed in COS-7 cells. Products that targeted to the plasma membrane were expressed in Xenopus oocytes for measurement of anion exchange activity. p.F335L, p.C565Y, p.L597S, p.M775T, and p.R776C had Cl(-)/I(-) and Cl(-)/HCO(3)(-) exchange rate constants that ranged from 13 to 93% of wild type values. p.F335L, p.L597S, p.M775T and p.R776C are typically found as mono-allelic variants in nonsyndromic EVA. The high normal control carrier rate for p.L597S indicates it is a coincidentally detected nonpathogenic variant in this context. We observed moderate differential effects of hypo-functional variants upon exchange of HCO(3)(-) versus I(-) but their magnitude does not support a causal association with nonsyndromic EVA. However, these alleles could be pathogenic in trans configuration with a mutant allele in Pendred syndrome.

Hedgehog signaling regulates sensory cell formation and auditory function in mice and humans.

Auditory perception is mediated through a finite number of mechanosensory hair cells located in a specialized sensory epithelium within the inner ear. The formation of the appropriate number of hair cells and the location of those cells is crucial for normal auditory function. However, the factors that regulate the formation of this epithelium remain poorly understood. Truncating mutations in the transcription factor GLI3, a downstream effector of the Hedgehog (HH) pathway, lead to a partial loss of HH signaling and cause Pallister-Hall syndrome (PHS). Here, we report that cochleae from a mouse model of PHS (Gli3(Delta699)), which produces only the truncated, repressor form of GLI3, have a variably penetrant phenotype that includes an increase in the size of the sensory epithelium and the development of large ectopic sensory patches in Kölliker's organ (KO). Consistent with the mouse model, some PHS individuals exhibit hearing loss across a broad range of frequencies. Moreover, inhibition of HH signaling in vitro results in an increase in the size of the prosensory domain, a precursor population that gives rise to the sensory epithelium, whereas treatment with Sonic hedgehog (SHH) inhibits prosensory formation. Finally, we demonstrate that HH signaling within the cochlea regulates expression of prosensory markers and that the effects of HH in KO are dependent on activation of Notch, an inducer of prosensory fate. These results suggest that HH signaling plays a key role in the specification, size, and location of the prosensory domain, and therefore of hair cells, within the cochlea.

Cochleosaccular dysplasia associated with a connexin 26 mutation in keratitis-ichthyosis-deafness syndrome.

OBJECTIVE: The objective of this study was to characterize the temporal bone phenotype associated with a mutation of GJB2 (encoding connexin 26). STUDY DESIGN: The authors conducted correlative clinical, molecular genetic, and postmortem histopathologic analysis. METHODS: The study subject was a male infant with keratitis-ichthyosis-deafness (KID) syndrome. We performed a nucleotide sequence analysis of GJB2 and a histopathologic analysis of the temporal bones. RESULTS: The subject was heterozygous for G45E, a previously reported KID syndrome mutation of GJB2. The primary inner ear abnormality was dysplasia of the cochlear and saccular neuroepithelium. CONCLUSIONS: GJB2 mutations can cause deafness in KID syndrome, and possibly in other GJB2 mutant phenotypes, by disrupting cochlear differentiation.

Investigation of the role of congenital cytomegalovirus infection in the etiology of enlarged vestibular aqueducts.

OBJECTIVE: To determine whether congenital cytomegalovirus (CMV) infection is an etiologic factor in the pathogenesis of enlarged vestibular aqueducts (EVA). DESIGN: Two different cohort studies. Subjects The study population comprised 19 subjects with a history of congenital CMV infection and sensorineural hearing loss (cohort 1); 39 subjects with nonsyndromic EVA and their unaffected mothers (cohort 2); and 16 control subjects with EVA associated with Pendred syndrome and bi-allelic mutations of the SLC26A4 gene and their unaffected mothers. RESULTS: In cohort 1, we detected EVA in 0 of 19 subjects with congenital CMV infection and sensorineural hearing loss. In cohort 2, anti-CMV serologic profiles were consistent with possible congenital CMV infection in 10 (26%) of 39 subjects with nonsyndromic EVA and 6 (38%) of 16 control subjects with Pendred syndrome (P = .52). These seroprevalence rates are similar to those expected in the general population (40%). CONCLUSION: In spite of their auditory phenotypic similarities, congenital CMV infection is not a significant factor in the etiology of EVA.