What is the etiology of hearing loss in a child?

Etiology of Hearing Loss in a Deaf Child

Genetic causes account for the majority of congenital hearing loss in children in developed countries, with approximately 50-60% of cases attributable to hereditary factors, while environmental causes including congenital infections (particularly cytomegalovirus), prematurity, and ototoxic medication exposure comprise the remainder. 1, 2, 3

Genetic Etiologies

Nonsyndromic Genetic Hearing Loss (70% of genetic cases)

• Autosomal recessive inheritance accounts for approximately 77% of nonsyndromic genetic hearing loss, typically presenting as profound prelingual deafness 1, 4
• Autosomal dominant inheritance represents 22% of cases, with more variable phenotypes and severity 1, 4
• X-linked inheritance comprises only 1% of nonsyndromic cases 1, 4
• Over 90% of children with autosomal recessive profound hearing loss are born to parents with normal hearing, making family history an unreliable screening tool 1, 4
• Mutations in the GJB2 gene (Connexin 26) account for more than half of all genetic cases in some populations, making it the single most common genetic cause 5, 6

Syndromic Genetic Hearing Loss (30% of genetic cases)

• Syndromic forms comprise 3-4% of all childhood hearing loss cases and include Waardenburg syndrome, Usher syndrome, Pendred syndrome, and Jervell and Lange-Nielsen syndrome 4, 7
• More than 400 syndromes associated with deafness have been described, often accompanied by outer ear malformations and/or systemic findings 7

Mitochondrial Inheritance

• Mitochondrial DNA variants may account for 1-20% of cases depending on population, with variable phenotypes 1, 4
• The m.1555A>G variant in the MT-RNR1 gene causes extreme sensitivity to aminoglycoside ototoxicity, even at therapeutic serum levels, and is present in less than 1% of the general US population 8, 5

Environmental and Acquired Etiologies

Congenital Infections

• Congenital cytomegalovirus (cCMV) is the most common infectious cause of hearing loss, prompting several states (Utah, Connecticut, Iowa, Virginia) to mandate cCMV screening after failed newborn hearing screening 1
• Congenital rubella was a common cause in the mid-1960s but now occurs rarely in Western populations due to successful immunization programs, with no endemic cases in the Americas between 2009-2012 1
• Other prenatal infections include syphilis, toxoplasmosis, and herpes 4
• Culture-positive postnatal bacterial and viral meningitis is a well-established risk factor for delayed-onset hearing loss 4

Perinatal Complications

• Prematurity, asphyxia, and complicated perinatal courses account for approximately 10% of bilateral sensorineural hearing loss 4
• Specific risk factors include NICU stay exceeding 5 days, ECMO, assisted ventilation, hyperbilirubinemia requiring exchange transfusion, and ototoxic medication exposure 4

Ototoxic Medications

• Aminoglycosides can cause total irreversible bilateral congenital deafness when administered during pregnancy, as they cross the placenta 8
• Aminoglycosides and cisplatin cause bilateral sensorineural hearing loss in children, often with concurrent vestibular loss and oscillopsia 4, 8
• Cochlear damage from aminoglycosides includes high-frequency deafness and usually occurs before clinical hearing loss can be detected 8

Structural and Traumatic Causes

• Craniofacial anomalies involving the pinna, ear canal, ear tags, ear pits, and temporal bone anomalies are associated with hearing loss 4
• Significant head trauma, basal skull/temporal bone fractures, and barotrauma can cause bilateral hearing loss 4

Metabolic and Mitochondrial Disorders

• MELAS (metabolic encephalopathy, lactic acidosis, and stroke-like episodes) presents with confusion, elevated lactate, MRI white matter changes, and hearing loss 4

Clinical Approach to Etiologic Diagnosis

Because genetic etiology is likely in most infants and children with hearing loss, clinical genetics evaluation including genetic counseling should be offered to every child with confirmed hearing loss 1

Key Diagnostic Considerations

• The distribution of causes varies significantly between developed and developing countries, with environmental and prenatal factors prevailing in low-income settings 2
• Genetic testing should prioritize GJB2 gene analysis first, given its high prevalence, followed by comprehensive hearing loss gene panels 6
• Testing for mitochondrial variants (particularly m.1555A>G) is critical to prevent future aminoglycoside-induced ototoxicity in the patient and at-risk relatives 1, 8
• Evaluation must assess for syndromic features through physical examination for craniofacial anomalies, pigmentary abnormalities, cardiac abnormalities, and renal anomalies 4, 7
• Congenital CMV testing should be performed in newborns with failed hearing screening, particularly in states with mandated screening protocols 1

Important Caveats

• The etiology of lesser degrees of hearing loss in the newborn period is not well understood, with most data focusing on profound hearing loss 1
• More than 77 loci for nonsyndromic hearing loss have been mapped, but many genes and mutations await discovery, meaning negative genetic testing does not exclude genetic etiology 1
• Different mutations at the same locus can cause both syndromic and nonsyndromic forms of deafness, complicating phenotype-genotype correlations 1
• Digenic interactions (mutations at two loci) are increasingly recognized, such as Connexin 26 heterozygotes with Connexin 30 deletions 5