Nonsyndromic deafness
Encyclopedia
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.
Genetic changes are related to the following types of nonsyndromic deafness.
Each type is 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 involves changes to the small amount of DNA
found in mitochondria, the energy-producing centers within cells.
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 bone
s that help transfer sound from the eardrum to the inner ear. Some forms of nonsyndromic deafness 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
.
, CDH23
, CLDN14
, COCH
, COL11A2
, DFNA5
, ESPN
, EYA4
, GJB2
, GJB6, KCNQ4
, MYO15A
, MYO6
, MYO7A
, OTOF
, PCDH15
, POU3F4
, SLC26A4, STRC
, TECTA
, TMC1
, TMIE, TMPRSS3
, USH1C
, and WFS1
genes cause nonsyndromic deafness, with weaker evidence currently implicating genes GJB3
, and MYO1A
.
The causes of nonsyndromic deafness can be 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. Gene mutations interfere with critical steps in processing sound, resulting in hearing loss. 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 families
, the gene(s) involved have yet to be identified.
Deafness can also result from environmental factors or a combination of genetic and environment
al factors, including certain medications, peri-natal infections (infections occurring before or after birth), and exposure to loud noise over an extended period.
Types include:
Another 20% to 25% 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% and 2% of cases show an X-linked pattern of inheritance, which means the mutated gene responsible for the condition is located on the X chromosome. 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. Fathers will not pass X-linked traits to their sons since they do not pass on the X chromosome to their male offspring.
Mitochondrial nonsyndromic deafness, which results from changes to the DNA in mitochondria, occurs in fewer than 1% of cases in the United States. The altered mitochondrial DNA is passed from a mother to her sons and daughters. This type of deafness is not inherited from fathers.
Late onset progressive deafness is the most common neurological disability of the elderly. Although hearing loss of greater than 25 decibels is present in only 1% of young adults between the ages of 18–24 years of age, this increases to 10% in persons between 55–64 years of age and approximately 50% in octogenarians.
The relative contribution of heredity to age –related hearing impairment is not known, however the majority of inherited late-onset deafness is autosomal dominant and non-syndromic (Van Camp et al., 1997). Over forty genes associated with autosomal dominant non-snydromic hearing loss have been localized and of these fifteen have been cloned.
Hearing impairment
-Definition:Deafness is the inability for the ear to interpret certain or all frequencies of sound.-Environmental Situations:Deafness can be caused by environmental situations such as noise, trauma, or other ear defections...
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.
Genetic changes are related to the following types of nonsyndromic deafness.
- DFNA: nonsyndromic deafness, autosomal dominant
- DFNB: nonsyndromic deafness, autosomal recessive
- DFNX: nonsyndromic deafness, X-linkedX chromosomeThe X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...
- nonsyndromic deafness, mitochondrial
Each type is 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 involves changes to the small amount of DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
found in mitochondria, the energy-producing centers within cells.
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
Cochlea
The cochlea is the auditory portion of the inner ear. It is a spiral-shaped cavity in the bony labyrinth, making 2.5 turns around its axis, the modiolus....
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
Sensorineural hearing loss
Sensorineural hearing loss is a type of hearing loss in which the root cause lies in the vestibulocochlear nerve , the inner ear, or central processing centers of the brain....
. Hearing loss that results from changes in the middle ear
Middle ear
The middle ear is the portion of the ear internal to the eardrum, and external to the oval window of the cochlea. The mammalian middle ear contains three ossicles, which couple vibration of the eardrum into waves in the fluid and membranes of the inner ear. The hollow space of the middle ear has...
is called conductive hearing loss. The middle ear contains three tiny bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
s that help transfer sound from the eardrum to the inner ear. Some forms of nonsyndromic deafness 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
Pitch (music)
Pitch is an auditory perceptual property that allows the ordering of sounds on a frequency-related scale.Pitches are compared as "higher" and "lower" in the sense associated with musical melodies,...
.
Nonsyndromic deafness can occur at any age. Hearing loss that is present before a child learns to speak is classified as prelingual
Prelingual deafness
A profoundly prelingually deaf individual is someone who was born with insufficient hearing to acquire speech normally, or who lost their hearing prior to the age at which speech is acquired....
or congenital. Hearing loss that occurs after the development of speech is classified as postlingual
Post-lingual deafness
Post-lingual deafness is a deafness which develops after the acquisition of speech and language, usually after the age of six.Post-lingual hearing impairments are far less common than prelingual deafness...
.
Epidemiology
About 1 in 1,000 children in the United States is born with profound deafness. By age 9, about 3 in 1,000 children have hearing loss that affects the activities of daily living. More than half of these cases are caused by genetic factors. Most cases of genetic deafness (70 % to 80 %) are nonsyndromic; the remaining cases are caused by specific genetic syndromes. In adults, the chance of developing hearing loss increases with age; hearing loss affects half of all people older than 80 years.Genes related to nonsyndromic deafness
Mutations in the ACTG1ACTG1
Actin, gamma 1, also known as ACTG1, is a gene.-Interactions:ACTG1 has been shown to interact with TMSB4X and CAP1.-Further reading:...
, CDH23
CDH23
Cadherin-23 is a protein that in humans is encoded by the CDH23 gene.-Further reading:...
, CLDN14
CLDN14
Claudin-14 is a protein that in humans is encoded by the CLDN14 gene. It belongs to the group of claudins.-Further reading:...
, COCH
COCH
Cochlin is a protein that in humans is encoded by the COCH gene.-Further reading:...
, COL11A2
COL11A2
COL11A2 is a human gene that is one of several genes that provide instructions for the production of type XI collagen. The COL11A2 gene produces one component of this type of collagen, called the pro-alpha2 chain...
, DFNA5
DFNA5
Non-syndromic hearing impairment protein 5 is a protein that in humans is encoded by the DFNA5 gene.-Further reading:...
, ESPN
Espin (protein)
Espin, also known as autosomal recessive deafness type 36 protein or ectoplasmic specialization protein, is a protein that in humans is encoded by the ESPN gene. Espin is a microfilament binding protein.- Function :...
, EYA4
EYA4
Eyes absent homolog 4 is a protein that in humans is encoded by the EYA4 gene.-Further reading:...
, GJB2
GJB2
Gap junction beta-2 also known as connexin-26 is a protein that in humans is encoded by the GJB2 gene. Defects in this gene lead to the most common form of congenital deafness in developed countries, called DFNB1, also known as Connexin 26 deafness or GJB2-related deafness.- Function :Gap...
, GJB6, KCNQ4
KCNQ4
Potassium voltage-gated channel subfamily KQT member 4 is a protein that in humans is encoded by the KCNQ4 gene.- External links :*...
, MYO15A
MYO15A
Myosin-XV is a protein that in humans is encoded by the MYO15A gene.-Further reading:...
, MYO6
MYO6
Myosin VI, also known as MYO6, is a protein. It has been found in humans, mice, fruit flies , and nematodes .-Interactions:MYO6 has been shown to interact with GIPC1 and DAB2....
, MYO7A
MYO7A
Myosin VIIA is protein that in humans is encoded by the MYO7A gene. Myosin VIIA is a member of the unconventional myosin superfamily of proteins...
, OTOF
OTOF
Otoferlin is a protein that in humans is encoded by the OTOF gene.-External links:* -Further reading:...
, PCDH15
PCDH15
Protocadherin-15 is a protein that in humans is encoded by the PCDH15 gene.-External Links:* -Further reading:...
, POU3F4
POU3F4
POU domain, class 3, transcription factor 4 is a protein that in humans is encoded by the POU3F4 gene. Mutations in POU3F4, located on the X chromosome, may cause deafness. The role of POU3F4 in the hypothalamus where it was originally described remains unknown....
, SLC26A4, STRC
STRC
Stereocilin is a protein that in humans is encoded by the STRC gene.-Further reading:...
, TECTA
TECTA
Alpha-tectorin is a protein that in humans is encoded by the TECTA gene.-Further reading:...
, TMC1
TMC1
Transmembrane channel-like protein 1 is a protein that in humans is encoded by the TMC1 gene.-Further reading:...
, TMIE, TMPRSS3
TMPRSS3
Transmembrane protease, serine 3 is an enzyme that in humans is encoded by the TMPRSS3 gene.-Further reading:...
, USH1C
USH1C
Harmonin is a protein that in humans is encoded by the USH1C gene.-External links:* -Further reading:...
, and WFS1
WFS1
Wolframin is a protein that in humans is encoded by the WFS1 gene.-Function:Wolframin is a transmembrane protein. Wolframin appears to function as a cation-selective ion channel.-Clinical significance:...
genes cause nonsyndromic deafness, with weaker evidence currently implicating genes GJB3
GJB3
Gap junction beta-3 protein is a protein that in humans is encoded by the GJB3 gene.- Function :This gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of...
, and MYO1A
MYO1A
Myosin-Ia is a protein that in humans is encoded by the MYO1A gene.The protein encoded by this gene belongs to the myosin superfamily. Myosins are molecular motors that, upon interaction with actin filaments, utilize energy from ATP hydrolysis to generate mechanical force. Each myosin has a...
.
The causes of nonsyndromic deafness can be 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. Gene mutations interfere with critical steps in processing sound, resulting in hearing loss. 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 families
Congenital disorder
A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...
, the gene(s) involved have yet to be identified.
Deafness can also result from environmental factors or a combination of genetic and environment
Environment (biophysical)
The biophysical environment is the combined modeling of the physical environment and the biological life forms within the environment, and includes all variables, parameters as well as conditions and modes inside the Earth's biosphere. The biophysical environment can be divided into two categories:...
al factors, including certain medications, peri-natal infections (infections occurring before or after birth), and exposure to loud noise over an extended period.
Types include:
| OMIM | Gene | Type |
|---|---|---|
Genetics
Nonsyndromic deafness can have different patterns of inheritance. Between 75% and 80% of cases are inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Usually, each parent of an individual with autosomal recessive deafness is a carrier of one copy of the altered gene. These carriers do not have hearing loss.Another 20% to 25% 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% and 2% of cases show an X-linked pattern of inheritance, which means the mutated gene responsible for the condition is located on the X chromosome. 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. Fathers will not pass X-linked traits to their sons since they do not pass on the X chromosome to their male offspring.
Mitochondrial nonsyndromic deafness, which results from changes to the DNA in mitochondria, occurs in fewer than 1% of cases in the United States. The altered mitochondrial DNA is passed from a mother to her sons and daughters. This type of deafness is not inherited from fathers.
Late onset progressive deafness is the most common neurological disability of the elderly. Although hearing loss of greater than 25 decibels is present in only 1% of young adults between the ages of 18–24 years of age, this increases to 10% in persons between 55–64 years of age and approximately 50% in octogenarians.
The relative contribution of heredity to age –related hearing impairment is not known, however the majority of inherited late-onset deafness is autosomal dominant and non-syndromic (Van Camp et al., 1997). Over forty genes associated with autosomal dominant non-snydromic hearing loss have been localized and of these fifteen have been cloned.
External links
- GeneReviews/NCBI/NIH/UW entry on Nonsyndromic Hearing Loss and Deafness, Mitochondrial
- GeneReviews/NCBI/NIH/UW entry on Nonsyndromic Hearing Loss and Deafness, DFNA3
- GeneReviews/NCBI/NIH/UW entry on Nonsyndromic Hearing Loss and Deafness, DFNB1
- GeneReviews/NCBI/NIH/UW entry on DFNX1 Nonsyndromic Hearing Loss and Deafness
- GeneReviews/NCBI/NIH/UW entry on OTOF-Related Deafness