StudyRareStudyRare
Presentations

Congenital sensorineural hearing loss

Log in to star
Hearing Presentations/Sensorineural hearing loss

Last updated 2mo ago

Log in to add personal notes on this page.

A newborn with a failed universal newborn hearing screen, confirmed by diagnostic auditory brainstem response (ABR) as sensorineural hearing loss (SNHL). Permanent congenital hearing loss occurs in roughly 1-3 per 1,000 newborns. Roughly half is genetic; of the genetic share, ~70% is non-syndromic and ~30% is syndromic. The acquired half is dominated by congenital CMV, the single most common non-genetic cause and the one that benefits from antiviral treatment when caught early. The diagnostic posture is to rule out CMV in the first three weeks (after that, distinguishing congenital from postnatal CMV becomes impossible from a single test) while running the genetic work-up in parallel.

Three questions structure the work-up:

  1. Is the loss isolated or are there other features? Syndromic clues: pigmentary anomalies (Waardenburg), branchial cleft anomalies or preauricular pits (BOR), hematuria or family history of kidney disease (Alport), syncope or family history of SCD (Jervell-Lange-Nielsen), goiter (Pendred), retinitis pigmentosa as the child grows (Usher).
  2. Is congenital CMV ruled in or out? Test within the first three weeks of life. After 21 days a positive test cannot reliably distinguish congenital from acquired infection.
  3. What is the family history? Many recessive forms have no prior family history (consanguinity raises pretest probability); a positive parental or sibling history with similar age of onset is a strong prior.

Non-syndromic SNHL (~70% of genetic)

  • GJB2-related hearing loss (connexin 26, AR): the single most common cause of non-syndromic hearing loss in many populations. The 35delG variant is common in European-ancestry populations; other prevalent variants in East Asian and African ancestry populations. Bilateral, prelingual, mild to profound.
  • GJB6 (connexin 30) deletions: large deletions in cis with a GJB2 variant cause a digenic recessive phenotype. Most GJB2 panels include GJB6 deletion screening.
  • SLC26A4 (pendrin): can be non-syndromic (DFNB4 with enlarged vestibular aqueduct on imaging) or syndromic (Pendred syndrome with goiter; below).
  • OTOF (otoferlin): auditory neuropathy phenotype; recognizable because OAEs are present but ABR is absent.
  • STRC, TMC1, MYO15A, CDH23, OTOA: other recessive non-syndromic loci, often on comprehensive panels.
  • KCNQ4, COCH, WFS1, TECTA: dominant non-syndromic forms with later or progressive onset.

Syndromic SNHL (~30% of genetic)

  • Pendred syndrome (SLC26A4, AR): SNHL + enlarged vestibular aqueduct (often with Mondini malformation) + euthyroid goiter (later childhood). The second most common syndromic cause overall.
  • Usher syndrome (multiple genes including MYO7A, USH2A, CDH23, PCDH15, CLRN1, AR):
    • Type 1: profound congenital SNHL + vestibular dysfunction + retinitis pigmentosa starting in childhood.
    • Type 2: moderate to severe congenital SNHL + normal vestibular function + later-onset RP.
    • Type 3: progressive postlingual SNHL + variable vestibular + RP.
    • The discriminating point: always send any genetic SNHL patient for baseline ophthalmologic evaluation to track RP progression.
  • Waardenburg syndrome (PAX3, MITF, EDN3, EDNRB, SOX10, SNAI2, AD mostly): pigmentary anomalies (white forelock, heterochromia iridum, premature graying) + dystopia canthorum (type 1) + SNHL + Hirschsprung disease in some types.
  • Alport syndrome (COL4A5 X-linked is most common, COL4A3/COL4A4 AR or AD): progressive SNHL + glomerular nephritis with hematuria + ocular anomalies (anterior lenticonus, dot-and-fleck retinopathy). Family history of kidney failure in young men is the clue.
  • Branchio-oto-renal (BOR) syndrome (EYA1, SIX1, SIX5, AD): branchial cleft fistulae or cysts + preauricular pits or tags + ear anomalies (microtia, conductive or mixed hearing loss) + renal anomalies (agenesis, hypoplasia, dysplasia).
  • Jervell-Lange-Nielsen syndrome (KCNQ1 or KCNE1, biallelic = AR): profound congenital SNHL + long QT + syncope + SCD risk. The discriminating contrast with Romano-Ward (AD long QT without deafness) is high-yield. Any deaf child with a syncopal episode gets an ECG today.
  • Stickler syndrome (COL2A1, COL11A1, COL11A2, AD mostly): SNHL or mixed loss + flat midface + Pierre Robin sequence + high myopia + vitreoretinal degeneration with retinal detachment risk.
  • CHARGE syndrome (CHD7): coloboma + heart + atresia of choanae + retardation + genital + ear anomalies including SNHL.
  • Mitochondrial hearing loss: MT-RNR1 m.1555A>G variant causes aminoglycoside-induced ototoxicity even at therapeutic doses. Screen any patient with hearing loss and aminoglycoside exposure.

Acquired (always on the differential)

  • Congenital CMV: the single most common non-genetic cause of permanent congenital hearing loss. Hearing loss may be present at birth or develop in the first months/years. Antiviral therapy (valganciclovir) for symptomatic congenital CMV improves hearing outcomes when started in the first month.
  • Other congenital infections: rubella, syphilis, toxoplasmosis, HSV.
  • Perinatal asphyxia, prematurity, hyperbilirubinemia, ototoxic medication exposure, meningitis (postnatal).
  • Bilateral profound SNHL in an otherwise well newborn with normal imaging → GJB2 first reach.
  • SNHL + enlarged vestibular aqueduct on temporal bone imaging → Pendred syndrome or non-syndromic SLC26A4. Goiter develops later.
  • SNHL + pigmentary anomalies (white forelock, heterochromia) → Waardenburg.
  • SNHL + family history of kidney failure in young men → Alport. Get a urinalysis.
  • SNHL + preauricular pits + branchial cleft fistulae → BOR. Renal ultrasound.
  • SNHL + syncope + family history of sudden death → Jervell-Lange-Nielsen. ECG today.
  • SNHL + flat midface + Pierre Robin + high myopia → Stickler.
  • SNHL in a child treated with gentamicin who lost hearing during therapy → m.1555A>G mitochondrial variant. Screen siblings and mother.
  • Present OAEs with absent ABR (auditory neuropathy) → OTOF otoferlin or hyperbilirubinemic injury.
  1. Confirmatory diagnostic ABR + OAE (the screen is just a screen). Audiologic characterization (severity, configuration, laterality).
  2. Congenital CMV testing in the first three weeks of life: urine CMV PCR or dried bloodspot PCR. After 21 days a positive test cannot reliably distinguish congenital from postnatal infection.
  3. Comprehensive non-syndromic and syndromic hearing-loss gene panel (first-tier GJB2 + GJB6 + SLC26A4, then comprehensive panel if negative; or comprehensive panel up front).
  4. Ophthalmologic examination (baseline and follow-up): Usher (RP), Alport (lenticonus, dot-and-fleck), Stickler (high myopia, vitreoretinal degeneration), Waardenburg (heterochromia).
  5. Renal ultrasound + urinalysis: BOR, Alport.
  6. 12-lead ECG: Jervell-Lange-Nielsen.
  7. Thyroid ultrasound or function tests as the child grows: Pendred goiter develops in late childhood or adolescence.
  8. Temporal bone CT or MRI: enlarged vestibular aqueduct (Pendred / DFNB4), Mondini malformation, cochlear nerve aplasia.
  9. Family pedigree with attention to consanguinity, similar hearing loss in relatives, kidney disease, sudden death, vision loss, thyroid disease.
  • The 21-day window for CMV testing is a hard deadline. Universal CMV screening at the same time as the newborn hearing screen is now standard in several US states for this reason.
  • Any genetic SNHL patient gets baseline ophthalmology. Usher syndrome reveals itself as RP in childhood; identifying it early lets families prepare and lets the patient consider cochlear implant timing in the context of future visual loss.
  • A deaf child with syncope or a family history of sudden death gets an ECG today. Jervell-Lange-Nielsen is the AR pairing of LQT and deafness; the diagnosis is missed at the family's peril.
  • Aminoglycoside exposure in a patient with maternal-line hearing loss is the m.1555A>G screen. A single dose can be enough to cause permanent profound loss.
  • Counseling is high-stakes here. Many families enter the work-up assuming "just hearing loss" and learn there is a syndromic, progressive, or systemic dimension. The counselor's framing matters.