Nonsyndromic deafness

Nonsyndromic deafness is hearing loss that is not associated with other signs and symptoms. In contrast, syndromic deafness involves hearing loss that occurs with abnormalities in other parts of the body. Different types of nonsyndromic deafness are named according to their inheritance patterns.

Most forms of nonsyndromic deafness are associated with permanent hearing loss caused by damage to structures in the inner ear. The inner ear consists of three parts: a snail-shaped structure called the cochlea that helps process sound, nerves that send information from the cochlea to the brain, and structures involved with balance. Loss of hearing caused by changes in the inner ear is called sensorineural deafness.

Hearing loss that results from changes in the middle ear is called conductive hearing loss. The middle ear contains three tiny bones that help transfer sound from the eardrum to the inner ear. Some forms of nonsyndromic deafness, particularly a type of deafness called DFN3, involve changes in both the inner ear and the middle ear. This combination is called mixed hearing loss.

The severity of hearing loss varies and can change over time. It can affect one ear (unilateral) or both ears (bilateral). Degrees of hearing loss range from mild (difficulty understanding soft speech) to profound (inability to hear even very loud noises). The loss may be stable, or it may progress as a person gets older. Particular types of nonsyndromic deafness often show distinctive patterns of hearing loss. For example, the loss may be more pronounced at high, middle, or low tones.

Nonsyndromic deafness can occur at any age. Hearing loss that is present before a child learns to speak is classified as prelingual or congenital. Hearing loss that occurs after the development of speech is classified as postlingual.

About 1 in 1,000 children in the United States is born with profound deafness, and another 2 to 3 per 1,000 children are born with partial hearing loss. More than half of these cases are caused by genetic factors. Most cases of genetic deafness (70 percent to 80 percent) are nonsyndromic; the remaining cases are caused by specific genetic syndromes.

In adults, the chance of developing hearing loss increases with age; hearing loss occurs in half of all people older than 80 years. Overall, 1 in 10 people in the United States—more than 28 million—are currently affected by hearing loss, and this number continues to increase as the population ages.

Nonsyndromic deafness is a condition related to changes in mitochondrial DNA.

Mutations in the ACTG1, CDH23, CLDN14, COCH, COL11A2, DFNA5, DFNB31, DFNB59, ESPN, EYA4, GJB2, GJB6, KCNQ4, LHFPL5, MT-TS1, MYO15A, MYO6, MYO7A, OTOF, PCDH15, POU3F4, SLC26A4, STRC, TECTA, TMC1, TMIE, TMPRSS3, TRIOBP, USH1C, and WFS1 genes cause nonsyndromic deafness.

Variations of the MT-RNR1 gene increase the risk of developing nonsyndromic deafness.

Variations in the ATP2B2 gene modify the course of nonsyndromic deafness.

The GJB3 and MYO1A genes are associated with nonsyndromic deafness.

The causes of nonsyndromic deafness are complex. Researchers have identified more than 30 genes that, when mutated, may cause nonsyndromic deafness; however, some of these genes have not been fully characterized. Many genes related to deafness are involved in the development and function of the inner ear. Mutations in these genes result in hearing loss by interfering with critical steps in processing sound. Different mutations in the same gene can cause different types of hearing loss, and some genes are associated with both syndromic and nonsyndromic deafness. In many affected families, the gene responsible for hearing loss has not been found.

Mutations in the GJB2 gene are a major cause of prelingual nonsyndromic deafness. This gene provides instructions for making a protein called connexin 26. The GJB6 gene also provides instructions for making a connexin protein, connexin 30. These proteins form parts (subunits) of channels called gap junctions, which allow communication between neighboring cells. Mutations in connexin proteins that make up gap junctions may affect the function or survival of cells that are needed for hearing.

DFN3 deafness is caused by mutations in the POU3F4 gene, which is located on the X chromosome. In people with this condition, one of the small bones in the middle ear (the stapes) cannot move normally, which interferes with hearing. This characteristic sign of DFN3 is called stapes fixation. At least four other regions of the X chromosome are involved in hearing loss, but the responsible genes have not been discovered.

Alterations in the MT-RNR1 and MT-TS1 genes have been found to increase the risk of developing nonsyndromic deafness. These genes are found in mitochondria, which are structures within cells that convert the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA (called mitochondrial DNA). People with particular mutations in the MT-RNR1 gene have an increased risk of hearing loss if they are exposed to certain antibiotic medications called aminoglycosides; however, some people with a mutation in the MT-RNR1 gene develop hearing loss even without exposure to these antibiotics.

Deafness can also result from environmental factors or a combination of genetic and environmental factors. Environmental causes of hearing loss include certain medications, specific infections before or after birth, and exposure to loud noise over an extended period.

Read more about the ACTG1, ATP2B2, CDH23, CLDN14, COCH, COL11A2, DFNA5, DFNB31, DFNB59, ESPN, EYA4, GJB2, GJB3, GJB6, KCNQ4, LHFPL5, MT-RNR1, MT-TS1, MYO15A, MYO1A, MYO6, MYO7A, OTOF, PCDH15, POU3F4, SLC26A4, STRC, TECTA, TMC1, TMIE, TMPRSS3, TRIOBP, USH1C, and WFS1 genes and mitochondrial DNA.

Nonsyndromic deafness can have different patterns of inheritance. Between 75 percent and 80 percent of cases are inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Usually, each parent of an individual with autosomal recessive deafness is a carrier of one copy of the mutated gene, but is not affected by this form of hearing loss.

Another 20 percent to 25 percent of nonsyndromic deafness cases are autosomal dominant, which means one copy of the altered gene in each cell is sufficient to result in hearing loss. People with autosomal dominant deafness most often inherit an altered copy of the gene from a parent who has hearing loss.

Between 1 percent and 2 percent of cases show an X-linked pattern of inheritance, which means the mutated gene responsible for the condition is located on the X chromosome (one of the two sex chromosomes). Males with X-linked nonsyndromic deafness tend to develop more severe hearing loss earlier in life than females who inherit a copy of the same gene mutation. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Mitochondrial nonsyndromic deafness, which results from changes to mitochondrial DNA, occurs in fewer than 1 percent of cases in the United States. The altered mitochondrial DNA is passed from a mother to all of her sons and daughters. This type of deafness is not inherited from fathers.

Types of nonsyndromic deafness are named according to their inheritance patterns. Autosomal dominant forms are designated DFNA, autosomal recessive forms are DFNB, and X-linked forms are DFN. Each type is also numbered in the order in which it was described. For example, DFNA1 was the first described autosomal dominant type of nonsyndromic deafness. Mitochondrial nonsyndromic deafness does not have a special designation.