Hereditary Hearing Loss (Non-Syndromic and Syndromic)
Hereditary hearing loss (HHL) refers to congenital or early-onset sensorineural hearing impairment caused by genetic mutations affecting the inner ear structures, hair cell function, or auditory nerve. It can occur either as an isolated defect (non-syndromic) or as part of a multisystem disorder (syndromic). Approximately 50–60% of congenital deafness is genetic in origin.
I. HEREDITARY NON-SYNDROMIC HEARING LOSS (NSHL)
Genetic and Molecular Basis
- Inheritance patterns:
- Autosomal recessive (AR): ~75–80% (congenital, severe–profound).
- Autosomal dominant (AD): ~15–20% (progressive, post-lingual).
- X-linked / mitochondrial: rare forms.
- Most common locus: DFNB1 – caused by mutations in:
- GJB2 gene (Connexin-26) and GJB6 (Connexin-30) on chromosome 13q11–12.
- These encode gap-junction proteins essential for potassium ion recycling within the cochlear hair cells.
Pathophysiology
- Connexin-26/30 gap-junction defects → impaired K⁺ ion homeostasis in the cochlea.
- Disturbed endocochlear potential → defective hair-cell depolarization.
- Leads to loss of cochlear hair cell function → sensorineural hearing loss.
- No structural abnormalities elsewhere → isolated deafness (non-syndromic).
Clinical Features
- Usually bilateral, symmetric sensorineural hearing loss.
- Onset: congenital or early infancy.
- Severity: moderate to profound (depending on mutation).
- No other organ involvement.
- Speech development delay common in children if untreated.