Isolated (Nonsyndromic) Hearing Loss

​​​​​This introductory information is not intended to replace a consultation with a healthcare provider. Please see NSGC.org  or Find a Genetic Service - Find Genetic Clinics (acmg.net)  to locate a Genetics healthcare provider near you. ​

​Approximately 70% of all genetic hearing loss occurs by itself (nonsyndromic) with no accompanying symptoms or medical issues. 

Deafness and hearing loss genes are named “DFN" for deafness.

  • “DFNB" for autosomal recessive forms​​
  • “DFNA” for autosomal dominant forms 
  • “DFN” when the altered gene lies on the X chromosome (X-Linked).  
  • mt if the gene is part of the mitochondrial DNA

A number follows DFNB, DFNA, or DFN

  • The number notes the order that the gene was found by researchers. 
  • There may be more than one number; this means that researchers originally thought there were multiple genes at this genetic position, but further testing showed the conditions to be caused by the same gene. An example of this is DFNB8/10 due to pathogenic variants in the TMPRSS3 gene. For more information, visit https://www.tmprss3.org.
  • Some genes can be inherited in both autosomal recessive and autosomal dominant ways. For example, different pathogenic variants in the TECTA gene can cause DFNB21 or DFNA8/12.    
  • Some genes cause both isolated (nonsyndromic) hearing loss and hearing loss combined with other symptoms (syndromic). For instance, different pathogenic variants in the MYO7A gene can cause DFNB3, DFNA11, or Usher type 1B.  

Common forms of isolated (nonsyndromic) hearing loss

Autosomal Recessive

GJB2 genes produce the Connexin 26 (CX26) protein. Pathogenic variants in GJB2 can result in autosomal recessive hearing loss.

GJB6 genes produce the Connexin 30 (CX30) protein. Pathogenic variants in GJB6 result in autosomal recessive hearing loss.

Hearing loss can be due to a pathogenic variant in GJB2 gene paired with a deletion of the GJB6 gene. This form of inheritance is called “Digenic or double heterozygosity” because pathogenic variants in two different genes cause the condition in one individual. 

    • DFNB1 is the most common form of childhood hearing loss, and may account for as many as 50% 
    • Hearing loss 

Present from birth (congenital) 

Both sides (bilateral) 

Tends to have the same degree and pattern of loss on both sides (symmetric)

Degree of hearing loss may vary among siblings

Although there is no consistent hearing loss pattern, roughly 50-80% of individuals have severe to profound hearing loss. 

Progression is seen in 30% of individuals.

No structural changes in the cochlea

    • Balance (vestibular function) should be normal.

DFNB16 Gene STRC Protein Stereocilia

Characteristics of STRC Hearing Loss

  • The most common cause of mild to moderate genetic hearing loss and may be as common as DFNB1 in some populations. 
  • Degree of hearing loss may vary among siblings.
  • Hearing loss is present in both ears (bilateral). 
  • No structural changes are seen with imaging such as CT or MRI.
  • Hearing loss is thought to be stable.
  • Stereocilin (STRC or DFNB16) hearing loss typically results when both STRC genes are missing (deleted).
  • Sometimes both STRC genes are missing along with a gene that lies next to it, CATSPER2. In males, when both STRC genes and both CATSPER2 genes are missing, the boy will have combined hearing loss and infertility. The CATSPER2 gene is partially responsible for sperm motility. Since girls and women do not make sperm, girls do not have infertility even when missing both CATSPER2 genes. 
  • See also Deafness Infertility Syndrome 

There are many other autosomal recessive non-syndromic hearing loss genes.​ See the TMPRSS3 Hearing Loss Resource Website at www.tmprss3.org.​​

Autosomal Dominant

Several genes (DFNA) are known to cause dominant non-syndromic hearing loss.​
  • Age of onset, degree of hearing loss, and rate of progression may vary even among family members.
  • Examples of autosomal dominant hearing loss:

Accounts for 9.5% of autosomal dominant non-syndromic hearing loss

Age of onset is early childhood to adolescence.

Hearing loss progresses from mild in low frequencies and moderate in high frequencies to moderate in low frequencies to profound in high frequencies by age 50.

  • TECTA DFNA8/12

Accounts for 2.9 to 4% of autosomal dominant non-syndromic hearing loss 

Age of onset is within the first ten years of life.

The frequency of the hearing loss depends somewhat on the location of the pathogenic variant.

Progression was not noted over a 10 year period in one study​.

There are many other autosomal dominant non-syndromic hearing loss genes

DFN​ X-Linked (Sex-Linked)

  • Due to a pathogenic variant in a gene located on the X chromosome
  • Several X-linked genes are associated with an isolated form of hearing loss.
  • Males tend to be more affected, while in some forms, female carriers may have symptoms.
  • The type and degree of hearing loss varies depending on the gene involved.

Examples of DFN hearing loss can be found at link

Mitochondrial

  • Mitochondrial DNA is in the mitochondria of the cell.
  • Mitochondrial DNA is passed in the egg from mothers to their children, but not by men to their children.
  • Examples:

A type of sensorineural hearing loss

May be progressive

May lead to sudden hearing loss when exposed to aminoglycoside antibiotics such as: neomycin, gentamycin, streptomycin, kanamycin, tobramycin, or amikacin)

  • ​​​​​​​​MT-TS1 (m.7445A>G)

Usually, childhood onset isolated hearing loss

Nonsyndromic Hearing Loss and Deafness, Mitochondrial - GeneReviews® - NCBI Bookshelf (nih.gov)​

Genetic Testing

Without genetic testing it is nearly impossible to diagnose the cause of isolated hearing loss (link to FAQs)