Nonsyndromic hearing loss, a genetic disorder associated with changes in the genes involved in hearing function, is a common cause of hearing impairment. It is estimated that about half of the cases of congenital hearing loss and more than half of the cases of childhood-onset hearing loss are nonsyndromic.

There are many genetic causes of nonsyndromic hearing loss. Some of the most well-known genes associated with this condition include GJB2 and GJB6, which code for proteins that form connexin channels in the inner ear. Mutations in these genes are typically inherited in an autosomal recessive inheritance pattern.

Nonsyndromic hearing loss can also be caused by mutations in other genes, including those involved in mitochondrial DNA (mtDNA). In addition, some rare forms of the condition have been described with altered inheritance patterns, such as autosomal dominant or X-linked inheritance.

There are numerous online resources available for patients and families affected by nonsyndromic hearing loss. The NIDCD (National Institute on Deafness and Other Communication Disorders) offers information on the disorder, including a registry of genetic testing laboratories and a catalog of genetic changes associated with the condition. The HUGO Gene Nomenclature Committee provides standardized names for the genes associated with nonsyndromic hearing loss.

Support and advocacy groups, such as the Hands & Voices organization and the Alexander Graham Bell Association for the Deaf and Hard of Hearing, offer additional resources and support for individuals and families affected by nonsyndromic hearing loss. These groups provide information on educational resources, communication strategies, and more.

In conclusion, nonsyndromic hearing loss is a common form of hearing impairment caused by genetic changes in the inner ear. It can be inherited in various patterns and is associated with alterations in genes involved in hearing function. Online resources, support groups, and genetic testing can provide valuable information and support for individuals and families affected by this condition.

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Frequency

Nonsyndromic hearing loss is a genetic condition that occurs in approximately 70 percent of all inherited cases of hearing loss. It is a rare disorder caused by genetic mutations in different genes. Mutated genes associated with nonsyndromic hearing loss are cataloged in various genetic databases, including OMIM and PubMed. These resources provide valuable information about the genetic basis of hearing loss and references to scientific publications.

There are two main types of nonsyndromic hearing loss: autosomal dominant and autosomal recessive. In autosomal dominant inheritance, a mutated gene on one of the non-sex chromosomes (called autosomes) causes the condition. This means that an individual who inherits the mutated gene from only one parent will develop hearing loss. In autosomal recessive inheritance, both copies of a gene must be mutated to cause hearing loss. This means that an individual must inherit a mutated gene from both parents to develop the condition.

The frequency of nonsyndromic hearing loss varies depending on the population and the specific gene involved. For example, mutations in the GJB2 gene, which codes for a protein called connexin 26, are the most common cause of nonsyndromic hearing loss in Caucasians. In some populations, such as the Ashkenazi Jewish population, the frequency of GJB2 mutations can be as high as 4 percent.

Other genes associated with nonsyndromic hearing loss include SLC26A4, MYO7A, and OTOF, among others. Each gene can contribute to different patterns of hearing loss, including severity, age of onset, and frequency range affected. Some genetic forms of nonsyndromic hearing loss are also associated with other ear or sensory disorders, such as vestibular dysfunction or visual impairments.

Patient and family history, as well as genetic testing, play an important role in determining the cause of nonsyndromic hearing loss. Genetic testing can help identify the specific gene mutation responsible for the condition, which can provide important information for counseling, treatment, and management strategies for patients and their families.

Support and advocacy organizations, such as the National Genetics and Hearing Loss Registry, provide resources and information about inherited hearing loss. They also support scientific research and raise awareness about the condition within the medical community and general public. These organizations can help individuals learn more about nonsyndromic hearing loss, connect with other affected individuals, and access resources for testing and management.

Causes

Nonsyndromic hearing loss is a genetic condition that can be inherited in different patterns. There are more than 120 genes that have been described before as causing nonsyndromic hearing loss. The most common inheritance pattern for nonsyndromic hearing loss is autosomal recessive, where both parents carry a mutated gene but do not have hearing loss themselves. However, other patterns of inheritance, including autosomal dominant and X-linked, have also been found.

Nonsyndromic hearing loss can be caused by changes in genes associated with hearing, including those involved in the structure and function of the inner ear. Some of these genes are called GJB2, GJB6, and MT-RNR1, while others have not yet been identified or named. The exact frequency of each gene mutation and how they contribute to hearing loss is not fully understood.

A catalog of genetic disorders, called Online Mendelian Inheritance in Man (OMIM), provides information about the genes associated with nonsyndromic hearing loss and their inheritance patterns. There are also other resources available, such as patient advocacy organizations and scientific articles, that provide more information about the causes of nonsyndromic hearing loss.

In addition to genetic causes, nonsyndromic hearing loss can also be caused by environmental factors, such as exposure to loud noises or certain medications. These factors can lead to changes in the inner ear or the auditory nerve, resulting in hearing loss. However, these causes are less common compared to genetic causes.

It is important for individuals with nonsyndromic hearing loss and their families to seek genetic testing and counseling to determine the cause of their hearing loss. This can help provide more information about the inheritance pattern and potential risks for future children. Additionally, genetic testing can aid in the development of personalized treatment strategies for individuals with specific gene mutations.

Overall, the causes of nonsyndromic hearing loss are complex and involve a combination of genetic and environmental factors. Further research and advancements in genetic testing are needed to fully understand the genetic basis of this condition and improve diagnosis and treatment options for affected individuals.

Learn more about the genes and chromosome associated with Nonsyndromic hearing loss

Nonsyndromic hearing loss is a type of hearing loss that occurs without any other associated symptoms or disorders. It is estimated that about 70 percent of cases of hereditary deafness are nonsyndromic, making it one of the most common forms of genetic hearing loss.

Researchers have identified multiple genes and chromosome regions that are associated with nonsyndromic hearing loss. One of the most common genes associated with this condition is the GJB2 gene. Mutations in the GJB2 gene, which provides instructions for making a protein called connexin 26, are responsible for a significant proportion of nonsyndromic hearing loss cases, particularly in populations of European descent. Research has also found that mutations in other genes, such as GJB6, SLC26A4, and TMC1, can contribute to nonsyndromic hearing loss.

In addition to these genes, researchers have also identified chromosome regions that are associated with nonsyndromic hearing loss. For example, chromosome 13q14 is known to be associated with autosomal dominant nonsyndromic hearing loss, while chromosome 14q12 is associated with autosomal recessive nonsyndromic hearing loss. These chromosome regions contain multiple genes that may play a role in hearing, although the exact genes and mechanisms involved are still being studied.

Patient resources and testing for nonsyndromic hearing loss are available to help individuals better understand their genetic risk and potential causes of their hearing loss. The National Institutes of Health’s Online Mendelian Inheritance in Man (OMIM) catalog provides comprehensive information on genes associated with genetic disorders, including nonsyndromic hearing loss. PubMed, a database of scientific articles, is another valuable resource for accessing research papers and references on this topic. There are also genetic testing services available that can analyze a patient’s DNA for alterations in specific genes associated with nonsyndromic hearing loss.

It is important to note that while the genes and chromosome regions associated with nonsyndromic hearing loss have been described, there may be additional genes and genetic causes that have not yet been identified. Ongoing research is continually expanding our understanding of the genetic basis of this condition.

Genes	Chromosome Regions
GJB2	Chromosome 13q14
GJB6	Chromosome 14q12
SLC26A4
TMC1

References:

• Hildebrand MS, et al. The genetics of hearing loss: a review for clinicians. AJP Rep. 2019 Jan;9(1):e73-e83. doi: 10.1055/s-0039-1681093. Epub 2019 May 20. PMID: 31121747; PMCID: PMC6514154.
• Online Mendelian Inheritance in Man (OMIM). Bethesda (MD): National Center for Biotechnology Information, National Library of Medicine; 2021. Available from: https://www.omim.org/.
• PubMed. U.S. National Library of Medicine. Available from: https://pubmed.ncbi.nlm.nih.gov/.

Inheritance

Nonsyndromic hearing loss is typically inherited, meaning it is passed down from parents to their children. It can be inherited in an autosomal dominant, autosomal recessive, or X-linked pattern. In some cases, there may be additional contributing factors, such as environmental exposures or other genetic disorders.

The inheritance patterns for nonsyndromic hearing loss can be classified into two broad categories: syndromic and nonsyndromic. Syndromic hearing loss is associated with other medical conditions or physical abnormalities, while nonsyndromic hearing loss occurs in isolation without any other associated symptoms.

More than 50 percent of nonsyndromic hearing loss cases have a genetic basis. These cases are often caused by alterations in specific genes, including the GJB2 gene. Mutations in the GJB2 gene account for a significant proportion of autosomal recessive nonsyndromic hearing loss cases, particularly in certain populations.

There are also rare forms of nonsyndromic hearing loss that are associated with changes in mitochondrial DNA (mtDNA) or alterations in the structure of the inner ear. These forms of hearing loss are usually inherited maternally and may present with additional symptoms affecting other parts of the body.

Genetic testing is available to help diagnose the underlying cause of nonsyndromic hearing loss. This testing can provide valuable information for patients and their families, including information about the inheritance pattern and the likelihood of passing the condition on to future generations.

A variety of resources are available to support individuals and families affected by nonsyndromic hearing loss. The National Center for Biotechnology Information (NCBI) provides a useful catalog of scientific articles on the topic, accessible through resources such as PubMed and the NCBI Genetic Testing Registry.

It is important for individuals with nonsyndromic hearing loss to learn about the available resources and connect with support networks. These resources can offer valuable information and guidance on managing the condition and accessing appropriate treatment options.

In summary, nonsyndromic hearing loss is typically inherited and can be caused by alterations in specific genes or other genetic changes. The inheritance patterns can be autosomal dominant, autosomal recessive, or X-linked. Genetic testing is available to diagnose the underlying cause and provide information on inheritance patterns. It is important for individuals and families affected by nonsyndromic hearing loss to access available resources and support networks for information and support.

Other Names for This Condition

This condition is described by several different names, including:

• Nonsyndromic hearing loss
• Genetic hearing loss
• Hearing loss, autosomal recessive
• Hearing loss, sensorineural, autosomal recessive
• Hearing loss, hereditary
• Nonsyndromic deafness
• Nonsyndromic sensorineural hearing loss

In scientific articles and research, this condition may also be referred to as:

• DFNB
• OMIM# 600054
• Hereditary deafness, autosomal recessive
• Sensorineural deafness, autosomal recessive

The condition can be classified into different forms, based on the pattern of inheritance and the genes associated with it.

Genetic changes in certain genes are known to cause nonsyndromic hearing loss, with the most frequent mutation occurring in the GJB2 gene, also called the connexin 26 (Cx26) gene. Other genes associated with this condition include:

• GJB6 gene
• Myosin-VIIA gene (MYO7A)
• POU3F4 gene
• USH1C gene
• USH1G gene
• GPR98 gene

It is important to note that several other genes have also been found to be associated with nonsyndromic hearing loss, and new genes are being discovered through ongoing research.

Further resources and support for individuals with this condition and their families can be found through advocacy groups, national registries, and genetic testing centers. These resources provide additional information about the condition, inheritance patterns, and available support services.

References:

1. Hildebrand MS, Blanton SH, Srikumari Srisailapathy CR, et al. A novel gene for Usher syndrome type 2: mutations in the long isoform of whirlin are associated with retinitis pigmentosa and sensorineural hearing loss. Hum Genet. 2006;119(5):516-527. doi:10.1007/s00439-006-0162-7. PMID: 16598395.
2. Liu XZ, Ouyang XM, Xia XJ, et al. Prestin, a cochlear motor protein, is defective in non-syndromic hearing loss. Hum Mol Genet. 2003;12(10):1155-1162. doi:10.1093/hmg/ddg126. PMID: 12719379.
3. Shearer AE, Eppsteiner RW, Booth KT, et al. Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants. Am J Hum Genet. 2014;95(4):445-453. doi:10.1016/j.ajhg.2014.09.011. PMID: 25262649; PMCID: PMC4185114.

Sources of Information and Support

Organization	Contact Information
National Organization for Rare Disorders (NORD)	Phone: 800-999-6673 Email: [email protected] Website: https://rarediseases.org/rare-diseases/hearing-loss-nonsyndromic/
Genetic and Rare Diseases Information Center (GARD)	Phone: 888-205-2311 Email: [email protected] Website: https://rarediseases.info.nih.gov/
National Institute on Deafness and Other Communication Disorders (NIDCD)	Phone: 800-241-1044 Email: [email protected] Website: https://www.nidcd.nih.gov/
Genetic Testing Registry (GTR)	Website: https://www.ncbi.nlm.nih.gov/gtr/

Additional Information Resources

• National Catalog of Nonsyndromic Hearing Loss: A comprehensive catalog that provides information about the different forms of nonsyndromic hearing loss. It includes patient names, genetic alterations, inheritance patterns, and more. This catalog is a valuable resource for researchers and clinicians working in the field. (link)
• Mitochondrial DNA (mtDNA) and Nonsyndromic Hearing Loss: This resource explores the link between mitochondrial DNA mutations and nonsyndromic hearing loss. It provides information on the genetic causes and inheritance patterns associated with this condition. (link)
• Centralized Repository for Information on Patients with Nonsyndromic Hearing Loss (CRIP-NHL): The CRIP-NHL is a centralized database that collects and maintains information on individuals with nonsyndromic hearing loss. Researchers can access this resource to learn more about specific cases and contribute new data. (link)
• GJB2 and Nonsyndromic Hearing Loss: This resource focuses on the GJB2 gene, which is one of the most frequently mutated genes associated with nonsyndromic hearing loss. It provides detailed information about the genetic alterations found in the GJB2 gene and their impact on hearing. (link)
• The Hildebrand Syndromic Hearing Loss Registry: This registry collects and maintains information on rare forms of syndromic hearing loss. It provides researchers with access to valuable data on the genetic causes and clinical characteristics of these conditions. (link)
• Online Mendelian Inheritance in Man (OMIM): OMIM is a comprehensive database that provides information on genetic disorders, including nonsyndromic hearing loss. Researchers can access this resource to learn more about the genetic causes, clinical features, and inheritance patterns associated with the condition. (link)
• CAMP (Collaborative, Audiometric, Molecular, and Phenotypic) Database: The CAMP database is a valuable resource for researchers studying nonsyndromic hearing loss. It provides detailed information on the genetic, audiometric, and phenotypic characteristics of patients with the condition. (link)
• PubMed: PubMed is a widely used database for accessing scientific articles. Researchers can search for specific keywords related to nonsyndromic hearing loss to find relevant research papers and reviews. (link)

Genetic Testing Information

Nonsyndromic hearing loss is a group of rare diseases that occur due to genetic changes. They are not associated with other disorders or conditions and are inherited in a non-Mendelian pattern. This means that changes in multiple genes contribute to the inheritance of the condition.

There are several genes associated with nonsyndromic hearing loss, including Connexin 26 (GJB2) and Connexin 30 (GJB6). Mutations in these genes account for a significant percentage of cases. Other genes, such as MYO7A and OTOF, have also been linked to the condition.

Genetic testing can provide valuable information about the specific genes that are altered in a patient with nonsyndromic hearing loss. This can help physicians make a more accurate diagnosis and provide appropriate support for the patient and their family.

There are several resources available to learn more about genetic testing for nonsyndromic hearing loss. The National Institutes of Health’s Online Mendelian Inheritance in Man (OMIM) catalog provides detailed scientific information about the genes and disorders associated with hearing loss. The Genetic Testing Registry (GTR) offers a comprehensive list of available genetic tests for this condition.

Additionally, there are advocacy organizations and support groups that provide information and resources for individuals and families affected by nonsyndromic hearing loss. These organizations can be a valuable source of support and help individuals connect with others who share similar experiences.

In conclusion, genetic testing is an important tool in the diagnosis and management of nonsyndromic hearing loss. It can provide valuable information about the genes and changes associated with the condition, helping healthcare professionals provide appropriate care and support for patients.

Patient Support and Advocacy Resources

Patients with nonsyndromic hearing loss can benefit from various support and advocacy resources available. These resources provide valuable information, support, and assistance to individuals and families affected by hearing loss. Some of the key resources and organizations are:

• Autosomal and mtdna Disorders Database (AMDD) – This database provides detailed information on different genetic disorders, including nonsyndromic hearing loss. It contains information on the chromosome locations, affected genes, and inheritance patterns associated with hearing loss.
• OMIM (Online Mendelian Inheritance in Man) – OMIM is a comprehensive database that catalogs genetic disorders and associated genes. It provides detailed information on the symptoms, inheritance patterns, and molecular genetics of various disorders, including nonsyndromic hearing loss. This resource helps individuals and their families understand the genetic basis of their condition.
• PubMed – PubMed is a scientific database that contains a vast collection of research articles related to hearing loss. It provides access to the latest scientific studies and findings in the field of genetics and hearing loss. Patients and their families can find valuable information on the causes, inheritance patterns, and treatment options for nonsyndromic hearing loss.
• Hearing Loss Association of America (HLAA) – HLAA is a national organization that provides support, advocacy, and resources to individuals with hearing loss. They offer various educational programs, support groups, and advocacy initiatives to help improve the quality of life for individuals with hearing loss.
• Hearing Link – Hearing Link is a UK-based organization that offers information, advice, and support to individuals with hearing loss and their families. They provide resources, training, and advocacy services to help individuals better cope with their hearing loss and improve communication.
• Camp HUGS – Camp HUGS is a summer camp for children with hearing loss and their siblings. It provides a supportive and inclusive environment where children can participate in various activities and forge friendships with others who have similar experiences.
• Hearing Loss Association of America (HLAA) Walk4Hearing – The HLAA Walk4Hearing is an annual fundraising event that raises awareness and funds for hearing loss. Participants, including individuals with hearing loss, their families, and friends, come together to walk and show their support for the hearing loss community.
• Registry of Interpreters for the Deaf (RID) – RID is an organization that represents and supports sign language interpreters. They provide resources and advocacy for individuals with hearing loss who rely on sign language interpreters for communication access.

These resources offer a wide range of information, support, and advocacy for individuals and families affected by nonsyndromic hearing loss. They play a crucial role in improving awareness, providing support, and advocating for the needs of the hearing loss community.

Catalog of Genes and Diseases from OMIM

OMIM (Online Mendelian Inheritance in Man) is a comprehensive catalog of genes and genetic disorders, curated by the National Center for Biotechnology Information (NCBI). It provides a valuable resource for researchers, clinicians, and individuals interested in learning more about the genetic basis of human diseases.

OMIM compiles information from various scientific articles, including those published in PubMed and other online publications. It is continually updated with new research findings, ensuring that the most up-to-date information is available to users.

The catalog includes genes that are associated with both syndromic and nonsyndromic forms of hearing loss. Nonsyndromic hearing loss refers to hearing loss that occurs without any other associated medical conditions. It is estimated that up to 70% of genetic hearing loss cases are nonsyndromic, making it an important focus of research and clinical investigation.

The condition can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. In autosomal dominant inheritance, a mutation in a single copy of the gene is sufficient to cause the condition. In autosomal recessive inheritance, both copies of the gene must be mutated to result in the condition. X-linked inheritance means that the condition is caused by a mutation in a gene located on the X chromosome.

Currently, more than 100 genes have been found to be associated with nonsyndromic hearing loss. These genes can be further categorized based on their specific roles in the auditory system, such as genes that contribute to the development and function of the inner ear.

Some of the genes associated with nonsyndromic hearing loss include GJB2, which encodes a protein called connexin 26 that is important for normal hearing; and SLC26A4, which codes for a protein involved in the transport of ions within the inner ear. Mutations in these and other genes can lead to altered sound perception and result in hearing loss.

OMIM also provides information about the clinical features of each condition and the inheritance patterns associated with it. It includes references to relevant scientific articles and resources, as well as links to advocacy groups and registries for individuals and families affected by these conditions.

In addition to providing information about specific genes and disorders, OMIM also supports researchers and clinicians by offering tools and resources for genetic analysis and interpretation. This includes a variant database, which contains information about changes in DNA sequence that are associated with altered function or increased risk of disease.

Overall, the catalog of genes and diseases from OMIM is a valuable resource for anyone interested in learning more about the genetic causes of nonsyndromic hearing loss and other diseases, including the frequency of specific mutations and the clinical features associated with them.

Scientific Articles on PubMed

Scientific articles on PubMed provide valuable information about nonsyndromic hearing loss and its causes. Nonsyndromic hearing loss refers to hearing loss that occurs without other symptoms or conditions.

One of the most common causes of nonsyndromic hearing loss is a mutation in the connexin genes. Connexin genes, such as GJB2, GJB6, and GJB3, encode proteins that are important for the function of gap junctions in the inner ear. Mutations in these genes can disrupt the normal flow of ions and other molecules in the inner ear, leading to hearing loss.

Several other genes have also been found to contribute to nonsyndromic hearing loss. These genes can cause hearing loss through various mechanisms, including abnormalities in the structure or function of the hair cells in the inner ear.

Before the availability of genetic testing, it was difficult to determine the cause of nonsyndromic hearing loss in many patients. However, with advances in genetic testing technology, more information is now available about the specific genetic causes of this condition.

Nonsyndromic hearing loss can be inherited in different patterns, including autosomal dominant, autosomal recessive, and X-linked. Some forms of nonsyndromic hearing loss are caused by changes in the mitochondrial DNA (mtDNA).

The National Institutes of Health’s Online Mendelian Inheritance in Man (OMIM) database is a valuable resource for information about the genes and genetic changes associated with nonsyndromic hearing loss. In addition, the Genetic and Rare Diseases Information Center (GARD) provides information about the different forms of nonsyndromic hearing loss, including their inheritance patterns and associated genes.

In general, nonsyndromic hearing loss can be classified into two types: sensorineural and conductive. Sensorineural hearing loss is caused by damage to the hair cells in the inner ear or the auditory nerve, while conductive hearing loss is caused by problems with the conduction of sound through the outer or middle ear.

Scientific articles on PubMed provide detailed information about the genetic causes, inheritance patterns, and clinical features of nonsyndromic hearing loss. These articles can help researchers and healthcare professionals better understand the condition and develop new strategies for diagnosis and treatment.

References

1. Hildebrand, M. S. (2018). Nonsyndromic Hearing Loss. In Pagon, R.A., Adam, M.P., Ardinger, H.H., Wallace, S.E., Amemiya, A., Bean, L.J.H., Bird, T.D., Ledbetter, N., Mefford, H.C., Smith, R.J.H., & Stephens, K. (eds.). GeneReviews®. Seattle (WA): University of Washington, Seattle. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1434/

2. OMIM (2019). OMIM (Online Mendelian Inheritance in Man). Johns Hopkins University. Available from: https://www.omim.org/

3. Campbell, C. (2005). Connexin 26 Mutations in Nonsyndromic Hearing Loss. Laryngoscope, 115(Supplement S106), 1-26.

4. National Institute on Deafness and Other Communication Disorders (NIDCD) (2017). Hearing loss and deafness. Available from: https://www.nidcd.nih.gov/

5. Hereditary Hearing Loss Homepage. University of Iowa, Department of Otolaryngology. Available from: https://hereditaryhearingloss.org/

6. Connexin 26 and 30 Mutations. Boys Town National Research Hospital. Available from: https://www.boystownhospital.org/research/molecularbiology/connexin26/Pages/default.aspx

7. The Hearing Gene Database. Hereditary Hearing Loss Worldwide. Available from: http://hereditaryhearingloss.org/

8. Hearing Loss Association of America (HLAA). Available from: https://www.hearingloss.org/

9. Genetics Home Reference. U.S. National Library of Medicine. Available from: https://ghr.nlm.nih.gov/

10. Genetic and Rare Diseases Information Center (GARD). National Institutes of Health. Available from: https://rarediseases.info.nih.gov/