Congenital sensory neural hearing loss
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Congenital Sensorineural Hearing Loss (SNHL)
Overview
Congenital SNHL affects 1-3 per 1,000 live births and is one of the most common congenital disabilities. The causes are broadly split 50:50 between genetic and acquired origins. Of genetic cases, 75% are non-syndromic and 25% are syndromic. - K.J. Lee's Essential Otolaryngology, p.1001; Bailey and Love's Surgery, p.781
1. Genetic Causes
A. Nonsyndromic (75% of genetic cases)
Autosomal Recessive (most common)
| Gene/Mutation | Mechanism | Key Features |
|---|---|---|
| GJB2 (Connexin 26) | Dysfunctional gap junctions impair K+ recycling in stria vascularis | Most common genetic cause; 35delG accounts for 80% of GJB2 mutations |
| GJB6 (Connexin 30) | Same pathway as above | Often co-inherits with GJB2 mutations |
| SLC26A4 (EVA) | Enlarged vestibular aqueduct | Mild-to-profound SNHL, can worsen with head trauma; flat or downsloping audiogram |
| OTOF (Otoferlin) | Vesicle membrane fusion defect | Auditory dyssynchrony: present OAEs, absent ABR |
| Mitochondrial A1555G | Mutation in mitochondrial 12S rRNA (maternally inherited) | 15% of US patients with aminoglycoside-induced SNHL; more prevalent in Mongolia |
Autosomal Dominant
- Wolfram syndrome: Most common cause of dominantly inherited low-frequency SNHL; progressive course.
B. Syndromic Genetic Causes (>400 syndromes)
Autosomal Recessive Syndromes
1. Pendred Syndrome
- Accounts for ~2% of profound congenital SNHL
- Mutation in SLC26A4 (iodine-chloride transporter defect)
- Bilateral/unilateral SNHL + Mondini malformation + euthyroid goiter
- Work-up: SLC26A4 testing, TSH, T3, T4
2. Usher Syndrome
- Affects 3% of the deaf population; 50% of the deaf-blind population
- Mutations in MYO7A, USH2A, and others (tip-link/usherin protein dysfunction)
- Three types:
- USH1 (most severe): profound SNHL, vestibular dysfunction, early retinitis pigmentosa
- USH2 (most common): moderate-severe SNHL, normal vestibular function, later retinitis pigmentosa
- USH3 (~3%, mostly Norwegian): progressive SNHL, variable vestibular function
3. Jervell and Lange-Nielsen
- 1 in 1,000 profoundly deaf patients
- Mutation in KVLQT1 - dysregulated potassium channel
- Severe/profound SNHL + prolonged QT interval + sudden death in young adults
- Treatment: beta-blockers; screen first-degree relatives for Romano-Ward syndrome
4. Biotinidase Deficiency
- Incidence: 1/60,000; screened in neonatal programs
- SNHL + hair loss + seizures + hypotonia
- Preventable/treatable with dietary biotin replacement
Autosomal Dominant Syndromes
1. Waardenburg Syndrome - Most common inherited congenital deafness (~2%)
- Mutation in neural crest cells → defective intermediate layer of stria vascularis
- Features: white forelock, dystopia canthorum, synophrys, heterochromia iridis, SNHL
- Four types: WS1 (PAX3), WS2A/Tietz (MITF), WS3 (Klein), WS4 (SOX10 + Hirschsprung)
2. Branchio-Oto-Renal (BOR) Syndrome
- EYA1 mutation (only 40% confirmed by testing)
- Major features: branchial clefts/fistulas, outer/middle/inner ear anomalies
- Temporal bone findings pathognomonic: fused malleoincudal complex, funnel-shaped IAC, hypoplastic cochlear apex
3. CHARGE Syndrome
- Sporadic microdeletion in CHD7 (chr 8) - only 50% have confirmed mutation
- Coloboma, Heart defects, Atresia choanae, Retardation, Genitourinary anomalies, Ear anomalies
- Inner ear: absent oval window, Mondini malformation, absent/hypoplastic semicircular canals
4. NF2 (Neurofibromatosis Type 2)
- Mutation in schwannomin (chr 22) → abnormal merlin protein
- Bilateral acoustic neuromas, hearing loss ~age 20, tinnitus, imbalance
5. Treacher-Collins (Mandibulofacial Dysostosis)
- Mutation in chr 5q → abnormal treacle protein
- Bilateral: microtia, aural atresia, mid-face hypoplasia, downsloping palpebral fissures, coloboma of lower eyelid, micrognathia
6. Stickler Syndrome
- Progressive mixed hearing loss (80%)
- Myopia, retinal detachment, cataracts, Robin sequence, hypermobile joints
X-Linked
1. Nonsyndromic - POU3F4 Mutation (Xq21)
- Most common X-linked deafness
- Males: stable hearing at birth → progressive mixed/SNHL (bilateral in 75%)
- Large IAC, absent lamina cribrosa; risk of perilymphatic gusher during surgery
2. Alport Syndrome
- COL4A5 mutation (X-linked) or COL4A3/COL4A4 (AR, 15%)
- Progressive high-frequency SNHL + glomerulonephritis + hematuria + anterior lenticonus
Chromosomal
- Down Syndrome (Trisomy 21): Stenotic EAC, middle ear disease, SNHL (common)
- Turner Syndrome (45,XO): Mixed conductive and SNHL
- Fetal Alcohol Syndrome: Microcephaly, mental retardation; conductive and SNHL
2. Acquired Causes
TORCH Infections
| Organism | Key Features |
|---|---|
| CMV (most common acquired cause in developed world) | Affects ~1% of pregnancies; 40% vertical transmission. IUGR, microcephaly, intracerebral calcification, SNHL (may be delayed onset, can be unilateral progressing to bilateral). Diagnose with PCR on neonatal dried blood spot |
| Rubella | CRS when maternal infection in first trimester; deafness + cataracts/glaucoma + PDA/pulmonary stenosis + microcephaly. Nearly eliminated in countries with vaccination |
| Toxoplasmosis | Part of TORCH screen |
| Syphilis (T. pallidum) | Vertical transmission 70-100% (primary stage); hearing loss is a late feature; congenital syphilis SNHL |
| Herpes | Part of TORCH spectrum |
Perinatal Causes
- Hypoxia / birth asphyxia
- Neonatal jaundice (kernicterus)
- Prematurity
Postnatal Causes
- Bacterial meningitis (Streptococcus most common organism)
- Mumps
3. Investigations / Diagnosis
| Test | Use |
|---|---|
| Newborn hearing screening | OAE (otoacoustic emissions) as first-pass screen; ABR (auditory brainstem response) for confirmation and thresholds |
| OAE | Tests outer hair cell function; present in auditory dyssynchrony (OTOF mutations) |
| ABR | Absent in otoferlin/auditory dyssynchrony despite present OAEs |
| Audiogram | Flat/downsloping in EVA; high-frequency loss in Alport |
| CT temporal bone | Mondini malformation, EVA, absent semicircular canals, funnel-shaped IAC |
| MRI | Cochlear nerve aplasia, CNS anomalies (CMV) |
| Genetic testing | GJB2/GJB6 first-line; SLC26A4 (Pendred/EVA); EYA1 (BOR); CHD7 (CHARGE); panel testing available |
| TORCH serology / PCR | CMV (PCR on dried blood spot preferred); rubella, syphilis serology |
| ECG | Prolonged QT for Jervell and Lange-Nielsen |
| Ophthalmology | Retinitis pigmentosa (Usher), lenticonus (Alport), coloboma (CHARGE) |
| Renal function / urinalysis | Hematuria in Alport syndrome |
| TSH, T3, T4 | Pendred (euthyroid goiter) |
4. Management
- Early identification - Universal newborn hearing screening programs are now standard (UK: OAE at birth; ABR if failed)
- Hearing aids - Fitting as early as possible to exploit neural plasticity of the developing auditory cortex
- Cochlear implantation - For profound SNHL; early intervention essential; stimulates cochlear neurones (which usually remain intact even when hair cells are lost); insertion through round window
- Auditory brainstem implant (ABI) - In cases of absent cochlear nerve (e.g., NF2, cochlear aplasia)
- Sign language / habilitation - Complementary to amplification
- Genetic counselling - Essential for families; test first-degree relatives
- Condition-specific management:
- Jervell-Lange-Nielsen: beta-blockers, screen relatives for Romano-Ward
- Pendred: monitor thyroid; avoid unnecessary thyroid surgery
- CMV: antiviral therapy (valganciclovir) may reduce progression of CMV-related SNHL
- Biotinidase deficiency: dietary biotin replacement
- K.J. Lee's Essential Otolaryngology, pp.1001-1006
- Bailey and Love's Short Practice of Surgery (28th ed.), p.781
- Scott-Brown's Otorhinolaryngology Head & Neck Surgery (Vol 2)
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