English terminology: Hereditary deafness. Frequency: Approximately 1 in 1,000 births; roughly 60% of cases involve genetic hearing loss.
Origins and Causes
Hearing loss can result from both genetic and environmental factors. It may occur due to perinatal infections (contracted during pregnancy or shortly after birth), acoustic or cerebral trauma, and the use of ototoxic medications that damage the ear. Deafness can present as the sole symptom (non-syndromic forms) or may accompany other signs and symptoms (syndromic forms).
In syndromic deafness, additional signs define specific clinical presentations including Alport syndrome, Waardenburg syndrome, Usher syndrome, and Pendred syndrome, among others less frequently encountered. This overview examines the genetic causes of non-syndromic deafness. For syndromic forms, consult specialized resources.
Identified Genes
The following table lists genes identified to date:
| Designation | Gene | Chromosome |
|---|---|---|
| DFNA1 | Diaphanous | 5 |
| DFNA2 | Connexin 31 | 1 |
| DFNA3 | Connexin 26 | 13 |
| DFNA5 | ICERE-1 | 7 |
| DFNA8 | Alpha-tectorin | 11 |
| DFNA9 | COCH | 14 |
| DFNA11 | Myosin 7A | 11 |
| DFNA12 | Alpha-tectorin | 11 |
| DFNA15 | POU4F3 | 5 |
| DFNB1 | Connexin 26 | 13 |
| DFNB2 | Myosin 7A | 11 |
| DFNB3 | Myosin 15 | 17 |
| DFNB4 | Pendrin | 7 |
| DFNB9 | Otoferlin | 2 |
| DFNB21 | Alpha-tectorin | 11 |
| DFN1 | DDP | X |
| DFN3 | POU3F4 | X |
| Mitochondrial | 12S rRNA | Mitochondrial |
| Mitochondrial | tRNA | Mitochondrial |
Most Frequently Altered Genes
Connexin 26 Gene
The connexin 26 gene (Cx26, also designated GJB2 - gap-junction protein beta 2), identified in 1997 with support from Telethon-funded research, accounts for most autosomal recessive deafness cases (in Italy and Spain, up to 80% of cases). Connexins are membrane proteins forming channels essential for cellular exchange and communication. This gene is involved in two distinct non-syndromic deafness forms: DFNB1 and DFNA3. While DFNA3 is quite rare, DFNB1 represents the most common autosomal recessive form. This is a congenital condition (present at birth) with moderate to profound hearing loss, generally non-progressive. Molecular analysis of the connexin 26 gene proves highly valuable for diagnosing congenital hereditary deafness.
COCH Gene
The COCH gene is likely the most frequently involved in autosomal dominant non-syndromic deafness (DFNA9). This progressive form initially affects high frequencies and involves balance disturbances (vertigo) due to inner ear structure involvement. The COCH gene's function remains partially understood, but deposits of long sugar molecules (mucopolysaccharides) have been documented in the inner ear of affected individuals, likely causing nerve fiber degeneration.
POU3F4 Gene
The POU3F4 gene is the major contributor to X-linked forms. Information encoded in this gene likely produces a factor important for nervous system development.
12S rRNA Gene
The 12S rRNA gene resides not on chromosomes but in mitochondrial DNA. It is responsible for the most common mitochondrial hereditary deafness form.
Inheritance Patterns
Multiple forms of genetic deafness exist with different transmission modes:
- Autosomal recessive in approximately 75% of cases
- Autosomal dominant in approximately 20%
- X-linked in approximately 5%
- Mitochondrial in less than 1%
Genes or chromosomal regions (loci) associated with various non-syndromic genetic deafness forms are designated with the DFN abbreviation (from English DeaFNess):
- DFNA for autosomal dominant heredity forms
- DFNB for autosomal recessive heredity forms
- DFN for X-linked recessive heredity forms
The designation is followed by a number indicating chronological identification order of genes or chromosomal regions. Precise determination of the total number of deafness genes remains impossible, as knowledge about deafness genetics is quite recent. Nineteen genes responsible for various hereditary deafness forms have been identified thus far. Many others remain unidentified, so at present, defining the specific deafness form and identifying the DNA alteration (mutation) responsible for the pathology is not always possible in affected individuals. Additionally, some forms are particularly rare, being described only in individual families.
Diagnosis
Beyond clinical and instrumental evaluation, physicians can use molecular analysis for diagnostic confirmation in cases where the gene responsible for the specific deafness form is known. Molecular analysis is generally performed from a small blood sample or cells scraped from inside the mouth, and permits DNA analysis to search for mutations in known genes. Molecular analysis can also be performed on family members of affected individuals to identify healthy mutation carriers. Since not all genes responsible for numerous hereditary deafness forms have been identified, molecular analysis does not always permit identification of the alteration causing the disease.
Early diagnosis and prenatal diagnosis can only be performed if the mutation responsible for the pathology has already been identified in affected family members.
Treatment Approaches
No definitive therapy exists for hereditary deafness forms. Treatment includes speech therapy rehabilitation and hearing aids (analog or digital); in selected cases, cochlear implantation may be performed.
Medical Centers
Several specialized genetics centers throughout Italy offer diagnostic services for hereditary deafness, including facilities in Florence, Genoa, San Giovanni Rotondo, Modena, Padua, and Ferrara.
Important Notice: The information contained on this page serves educational purposes only. Although written by qualified personnel, this content cannot substitute the opinion of your treating physician in decisions and choices regarding your health.