Clinical evaluation and etiologic diagnosis of hearing loss: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)

Li, Marilyn M.; Tayoun, Ahmad Abou; DiStefano, Marina T.; Pandya, Arti; Rehm, Heidi L.; Robin, Nathaniel H.; Schaefer, Amanda M.; Yoshinaga-Itano, Christine

doi:10.1016/j.gim.2022.03.018

Cited by 23 publications

(16 citation statements)

References 140 publications

(190 reference statements)

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“…24 Four experienced reviewers (R.J.C., T.W., A.A., and M.C.K.) independently interpreted all variants using the guidelines of the American College of Medical Genetics and Genomics 25 and best practices for expert interpretation of genomic data. 26 Variants were interpreted as potentially damaging if they were truncating, were predicted to lead to a loss of transcript, completely deleted a critical gene, or were missense with a predicted negative functional effect.…”

Section: Meaningmentioning

confidence: 99%

Association of Genetic Diagnoses for Childhood-Onset Hearing Loss With Cochlear Implant Outcomes

Carlson

Walsh

Mandell

et al. 2023

JAMA Otolaryngol Head Neck Surg

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ImportanceIn the US, most childhood-onset bilateral sensorineural hearing loss is genetic, with more than 120 genes and thousands of different alleles known. Primary treatments are hearing aids and cochlear implants. Genetic diagnosis can inform progression of hearing loss, indicate potential syndromic features, and suggest best timing for individualized treatment.ObjectiveTo identify the genetic causes of childhood-onset hearing loss and characterize severity, progression, and cochlear implant success associated with genotype in a single large clinical cohort.Design, Setting, and ParticipantsThis cross-sectional analysis (genomics) and retrospective cohort analysis (audiological measures) were conducted from 2019 to 2022 at the otolaryngology and audiology clinics of Seattle Children’s Hospital and University of Washington and included 449 children from 406 families with bilateral sensorineural hearing loss with an onset younger than 18 years. Data were analyzed between January and June 2022.Main Outcomes and MeasuresGenetic diagnoses based on genomic sequencing and structural variant analysis of the DNA of participants; severity and progression of hearing loss as measured by audiologic testing; and cochlear implant success as measured by pediatric and adult speech perception tests. Hearing thresholds and speech perception scores were evaluated with respect to age at implant, months since implant, and genotype using a multivariate analysis of variance and covariance.ResultsOf 406 participants, 208 (51%) were female, 17 (4%) were African/African American, 32 (8%) were East Asian, 219 (54%) were European, 53 (13%) were Latino/Admixed American, and 16 (4%) were South Asian. Genomic analysis yielded genetic diagnoses for 210 of 406 families (52%), including 55 of 82 multiplex families (67%) and 155 of 324 singleton families (48%). Rates of genetic diagnosis were similar for children of all ancestries. Causal variants occurred in 43 different genes, with each child (with 1 exception) having causative variant(s) in only 1 gene. Hearing loss severity, affected frequencies, and progression varied by gene and, for some genes, by genotype within gene. For children with causative mutations in MYO6, OTOA, SLC26A4, TMPRSS3, or severe loss-of-function variants in GJB2, hearing loss was progressive, with losses of more than 10 dB per decade. For all children with cochlear implants, outcomes of adult speech perception tests were greater than preimplanted levels. Yet the degree of success varied substantially by genotype. Adjusting for age at implant and interval since implant, speech perception was highest for children with hearing loss due to MITF or TMPRSS3.Conclusions and RelevanceThe results of this cross-sectional study suggest that genetic diagnosis is now sufficiently advanced to enable its integration into precision medical care for childhood-onset hearing loss.

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Section: Meaningmentioning

confidence: 99%

Association of Genetic Diagnoses for Childhood-Onset Hearing Loss With Cochlear Implant Outcomes

Carlson

Walsh

Mandell

et al. 2023

JAMA Otolaryngol Head Neck Surg

View full text Add to dashboard Cite

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“…Genetic testing is not typically recommended for the evaluation of children with unilateral or asymmetric HL due to previously reported low diagnostic yields 6,7 . For these children, we and others have suggested an imaging‐first approach to detect structural (cochleovestibular) anomalies 8 .…”

Section: Introductionmentioning

confidence: 99%

“…Genetic testing is not typically recommended for the evaluation of children with unilateral or asymmetric HL due to previously reported low diagnostic yields. 6,7 For these children, we and others have suggested an imaging-first approach to detect structural (cochleovestibular) anomalies. 8 The diagnostic yield of thin-cut computed tomography of the temporal bones and/or magnetic resonance imaging has been shown to be approximately 30% for these patients.…”

Section: Introductionmentioning

confidence: 99%

Exome Sequencing Expands the Genetic Diagnostic Spectrum for Pediatric Hearing Loss

et al. 2022

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ObjectivesGenetic testing is the standard‐of‐care for diagnostic evaluation of bilateral, symmetric, sensorineural hearing loss (HL). We sought to determine the efficacy of a comprehensive genetic testing method, exome sequencing (ES), in a heterogeneous pediatric patient population with bilateral symmetric, bilateral asymmetric, and unilateral HL.MethodsTrio‐based ES was performed for pediatric patients with confirmed HL including those with symmetric, asymmetric, and unilateral HL.ResultsES was completed for 218 probands. A genetic cause was identified for 31.2% of probands (n = 68). The diagnostic rate was 40.7% for bilateral HL, 23.1% for asymmetric HL, and 18.3% for unilateral HL, with syndromic diagnoses made in 20.8%, 33.3%, and 54.5% of cases in each group, respectively. Secondary or incidental findings were identified in 10 families (5.52%).ConclusionES is an effective method for genetic diagnosis for HL including phenotypically diverse patients and allows the identification of secondary findings, discovery of deafness‐causing genes, and the potential for efficient data re‐analysis.Level of Evidence4 Laryngoscope, 133:2417–2424, 2023

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“…Patients who present with both bilateral SNHL and severe CHD should undergo a prioritized test for SNHL followed by a supplemental test for CHD. The recommended genetic testing strategies for CHD 32,33 and for SNHL 34 have been described elsewhere. More extended testing with whole exome sequencing (WES) is recommended if the previous tests do not yield positive results, with whole genome sequencing (WGS) considered in selected patients or patients with negative WES results.…”

Section: Genetic Counseling For Co-occurring Snhl and Chdmentioning

confidence: 99%

Co‐Occurrence of Sensorineural Hearing Loss and Congenital Heart Disease: Etiologies and Management

Yang

Fan

et al. 2023

The Laryngoscope

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Objectives/HypothesisThe co‐occurrence of sensorineural hearing loss (SNHL) and congenital heart disease (CHD) is a rare condition with complex etiologies. The purpose of this study is to assess the etiologies, clinical features, and outcomes of cochlear implant (CI) in this patient population.Study DesignCase series and literature review.MethodsClinical data of children who were diagnosed with SNHL and CHD and received CIs at a tertiary hospital from 2016 to 2021 were retrospectively analyzed. A literature review was performed to identify patients with SNHL and CHD.FindingsOf the 382 children who underwent cochlear implantation at our center, eight (2.1%) were diagnosed with SNHL and CHD. A literature review identified 1525 patients from 254 studies; the database therefore consisted of 1533 patients. The most common genetic etiologies of co‐occurring SNHL and CHD were CHARGE syndrome (36.3%), Turner syndrome (8.4%), 22q11.2 deletion (3.0%), Noonan syndrome (2.9%), and Down syndrome (2.5%), whereas the most common non‐genetic etiologies were congenital rubella syndrome (22.9%) and SNHL after early cardiac surgery (5.5%). Most of the patients presented with congenital, bilateral, severe‐profound SNHL requiring early rehabilitation. Of the 126 children who received CIs at a median age of 2.5 years, half showed delayed speech development at last follow‐up.ConclusionsCo‐occurring SNHL and CHD is a rare condition with complex etiologies. Timely hearing intervention with long‐term follow‐up and proper timing of heart surgery is essential for these children.Level of Evidence4, case series Laryngoscope, 2023

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Clinical evaluation and etiologic diagnosis of hearing loss: A clinical practice resource of the American College of Medical Genetics and Genomics (ACMG)

Cited by 23 publications

References 140 publications

Association of Genetic Diagnoses for Childhood-Onset Hearing Loss With Cochlear Implant Outcomes

Association of Genetic Diagnoses for Childhood-Onset Hearing Loss With Cochlear Implant Outcomes

Exome Sequencing Expands the Genetic Diagnostic Spectrum for Pediatric Hearing Loss

Co‐Occurrence of Sensorineural Hearing Loss and Congenital Heart Disease: Etiologies and Management

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