January 17, 2006 Feature

Genetics and Hearing Loss: An Overview

Knowing the exact cause of a child's hearing loss can assist clinicians and parents in making decisions regarding treatment and educational options. It may surprise some parents to know that more than half of all children who are born deaf or who become deaf very early in life have a genetic cause for their hearing loss. In fact, recent  studies have revealed that approximately 50-60% of moderate to profound, congenital, or early-onset hearing loss is genetic. The remaining 40-50% of hearing loss is due to non-genetic effects, such as maternal infection (CMV or rubella), prematurity, postnata infection (meningitis, otitis media), ototoxic drugs, or acoustic/ cranial trauma.

Genetic forms of hearing loss result from changes in the genetic material. The genetic material, called DNA (deoxyribonucleic acid), is contained in almost every cell in the human body. The long chains of DNA can be divided into sections, called genes. Each person inherits two copies of each gene, one from each parent. Genes control the production and function of proteins, which form the structural and regulatory elements of the body. Genes, composed of a specific sequence of the chemical units adenine (A), guanine (G), cytosine (C), and thymine (T), are fairly consistent from person to person. Estimates suggest that humans have approximately 30,000 genes, of which at least 10% are involved in determining the structure and function of the ear. Recent progress in identification of these genes has provided insight into how the ear functions and how mutations in a single gene can cause hearing loss.

More than 400 different forms of hereditary hearing loss are known. Many of these forms can be distinguished from one another by audiologic characteristics (type, degree, or progression), vestibular characteristics, mode of inheritance, or the presence of other medical or physical characteristics. In the majority of cases (60-70%), hearing loss occurs as an isolated finding and is referred to as non-syndromic. The remaining 30-40% of hereditary hearing loss is syndromic, resulting from a mutation in a gene that affects the development of multiple organs. Some common syndromes associated with hearing loss are described in Table 1, however the complete list of genetic syndromes associated with hearing loss is long and complex. Although it is not essential that professionals who work with deaf children be familiar with all of the features of syndromic forms of hearing loss, an appreciation of the complexity of these disorders and the effect they can have on the health of these individuals as well as family members (siblings and offspring) emphasizes the importance of providing referrals for genetic evaluation and encouraging families to follow through with the referrals.

Genetic forms of hearing loss can also be classified by inheritance pattern. When only one copy of a mutation in a gene is necessary to cause hearing loss, the trait is inherited in a dominant pattern. Approxi-mately 10-20% of non-syndromic deafness is inherited in a dominant manner. When two copies of a mutation in the same gene (one from each parent) are necessary to cause hearing loss, the trait is inherited in an autosomal recessive pattern. Roughly 70-80% of hearing loss is inherited in an autosomal recessive pattern. When recessive genes for deafness are located on the X chromosome, the trait is inherited as X-linked recessive. A small percentage, around 1-2%, of hearing loss can be attributed to X-linked recessive inheritance.

Mitochondrial inheritance refers to the inheritance of a genetic mutation in the genes contained within the mitochondria. The mitochondria contain a small amount of DNA (37 genes) which is passed on to the next generation only through the egg cell. Thus, mitochondrial mutations are only inherited from the mother and are passed on to all of her children. These mutations may account for 0-20% of inherited hearing loss, depending on ethnic background.

The most common form of hereditary deafness is caused by mutations in the GJB2 gene. This gene, which encodes the gap junction beta protein connexin 26, is most commonly inherited in an autosomal recessive fashion. Hearing loss which results from mutations in the GJB2 gene varies in degree and progression, but most individuals have congenital, profound, stable sensorineural hearing loss. Between 10-37% of individuals with an "unknown" cause for their deafness have mutations in GJB2.

A genetic evaluation can often identify the exact cause of hearing loss or at the very least, exclude many causes of the hearing loss. At some point after the identification of their hearing loss, most children can benefit from a genetic evaluation. In 2002, the American College of Medical Genetics (ACMG) published a statement entitled "Genetic Evaluation Guidelines for the Etiologic Diagnosis of Congenital Hearing Loss."

In this statement, the ACMG emphasized that the appropriate management of all persons identified with congenital hearing loss requires a comprehensive genetic evaluation. The genetic evaluation should include a detailed family history, a complete physical examination, a thorough patient history, and examinations by other medical specialists, when necessary. During genetic evaluation and counseling the geneticist and/or genetic counselor will assist patients and families with the diagnosis of a genetic condition, identify associated medical issues and provide referrals for medical management. The geneticist/genetic counselor will also calculate and communicate the recurrence risk and provide psychosocial support for the family.

Audiologists can play an essential role in the process of genetic diagnosis. Whether providing the initial referral to genetic services, helping to reinforce or correct misinformation, or by identifying those in need of additional support, the audiologist is an important member of the health care team.

Audiologists, speech-language pathologists, and other interested professionals may obtain additional information about genetics and/or the Gallaudet University Genetics Program by viewing the Web site.

[Editor's note: Arnos, Pandya, and Burton gave the audiology keynote focused on genetics Nov. 18, 2005 at the ASHA Convention in San Diego.]

Kathleen S Arnos, is director of the genetics program and professor of biology at Gallaudet University in Washington, DC. She is currently the principal investigator of two NIH- funded projects to provide education in genetics to faculty of audiology education programs and to investigate hereditary deafness in the alumni of Gallaudet University.

Arti Pandya, is a pediatric geneticist at Virginia Commonwealth University. She is the principal investigator of two NIH-funded projects to map novel genes for hereditary deafness and to investigate the societal impact of testing for genes for deafness.

Sarah Burton, is a genetic counselor at Gallaudet University and the program coordinator for the summer program in genetics for audiology faculty. She is the research coordinator for the project entitled Potential Societal Impact of Advances in Genetic Deafness.

cite as: Arnos, K. S. , Pandya, A.  & Burton, S. (2006, January 17). Genetics and Hearing Loss: An Overview. The ASHA Leader.

Keynote Table

Table 1 Common Syndromic Forms of Hearing Loss 

Syndrome Inheritance Features
Waardenburg autosomal dominant with variable expression white forelock, moderate to profound unilateral or bilateral sensorineural deafness, vitiligo, hypopigmentation, and/or differently colored eyes or bright blue eyesType I includes the appearance of widely spaced eyes (dystopia canthorum)
Treacher-Collins autosomal dominant with variable expression downward sloping eye openings, flattened cheek bones, malformed or absent outer ears, small chin, coloboma (notch) of the lower eyelid, and conductive hearing loss
Branchio-oto-renal (BOR) autosomal dominant with variable expression sensorineural, conductive or mixed hearing loss with ear pits, fistulas or cysts of the neck; altered ear shape, and/or structural or functional changes in the kidney
Usher autosomal recessive sensorineural deafness with retinitis pigmentosa (a progressive disease of the rod cells in the retina resulting in visual impairment); vestibular dysfunction in some types
Jervell and Lange-Nielsen (JLN) autosomal recessive congenital sensorineural hearing loss associated with a heart defect, specifically a prolonged QT interval on EKG placing these individuals at risk for sudden death
Pendred autosomal recessive sensorineural hearing loss (may be progressive), goiter (usually euthyroid), enlarged vestibular aqueduct and/or Mondini dysplasia



References

Genetic Evaluation of Congenital Hearing Loss Expert Panel. (2002). Genetics evaluation guidelines for the etiologic diagnosis of congenital hearing loss. Genetics in Medicine, 4(3), 162-171.

Marazita, M. L., Ploughman, L. M., Rawlings, B., Remington, E., Arnos, K. S. & Nance, W. E. (1993). Genetic epidemiological studies of early-onset deafness in the U.S. school-age population. American Journal of Medical Genetics, 46, 486-491.

Gorlin, R. J., Torielo, H. V. & Cohen, M. M. (1995). Hereditary hearing loss and its syndromes. New York: Oxford University Press.

Tekin, M. Arnos, K.S. & Pandya, A. (2001). Advances in hereditary deafness. Lancet, 358, 1082-1090.

ASHA Resources

Elfenbein, Jill L. (2003). Genetics of hearing loss: Contributions of mitochondrial DNA. Perspectives on Aural Rehabilitation and Its Instrumentation, 10(1), 2-5. Special Interest  Division 7.

Keats, B. (2005, Sept. 6). Genetics and hearing loss. The ASHA Leader, pp. 6-7, 16-18.

Mason, P. (Ed.). (2003). Hot topic: Genetics and hearing loss. Access Audiology, Vol. 2, No. 3. Available from www.asha.org/members/aud/ access-aud-online/AAUD0503.



  

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