Hereditary hearing loss and deafness
Hereditary hearing loss and deafness refers to the genetically caused loss or partial impairment of the ability to hear. It is estimated that at least half of the people with hearing loss and/or deafness in the developed world have it as the result of genetic causes.
Genetic forms of hearing loss can be congenital (present from birth) or delayed onset. These hearing losses can be progressive, in which the hearing impairment increases with time; or non-progressive, in which the hearing loss is stable over time. Both ears (bilateral) or only one ear (unilateral) may be affected and the hearing loss may be equal in both ears (symmetric) or different in
Conductive hearing loss results from a blockage of the auditory canal or some other dysfunction of the eardrum or one of the three small bones within the ear (the stapes, the malleus, and the incus) that are responsible for collecting sound. In hearing, sound vibrations enter the large fleshy part of the ear that is external to the head (the pinna) and travel down the auditory canal striking the eardrum (tympanic membrane), which begins to vibrate. As this membrane vibrates it touches the first of a series of three small bones (the malleus, the incus, and the stapes) that mechanically transfer the vibrations to the cochlea. The cochlea is a fluid-filled tube that bends back on itself such that the two open ends lie one on top of the other. One end is covered by a membrane called the oval window, while the other end is covered by a membrane called the round window. It is the oval window that is struck by the stapes. Since the cochlea is filled with fluid, the oval window cannot vibrate without the assistance of the round window: as the oval window is pushed in by the stapes, the round window bulges out; as the oval window oscillates out, the round window bulges inward.
The vibrations imparted to the oval window by the stapes striking the round window are picked up by the organ of Corti within the cochlea. It is this structure that is the true receptor, in a nerve sense, of sound waves. The organ of Corti consists of hair cells embedded in a gelatinous membrane (the tectorial membrane) that rest on a basilar membrane. Sensory neurons terminate on the hair cells of the organ of Corti. Vibration of the fluid in the cochlea causes the basilar membrane to move, which causes the hairs to bend creating an electrical signal. This is picked up by the sensory neurons and transferred to the auditory nerve (or cochlear nerve), which sends the impulse to the brain. Sensorineural hearing loss results from a dysfunction of the auditory nerve. In conductive hearing loss, the auditory nerve is normal.
Mixed type hearing loss involves both conductive and sensorineural types of hearing impairment.
The ear is also involved in maintaining balance. As a result, many individuals affected with hearing loss may also have balance problems. Body position, body movement, and balance are assisted by the vestibular apparatus of the inner ear, which consists of three functional parts. Two of these, the saccule and the utricle, signal what the body position is relative to gravity. The third structure of the vestibular apparatus is the semicircular canal, of which there are three in each ear. These canals contain structures (ampulae) that detect movement of the internal fluid of the canals as the head moves. Most hearing impaired people with balance problems experience difficulties with the proper functioning of the semicircular canals. Since the function of these canals is partially duplicated by the functioning of the saccule and the utricle, most individuals can "learn" to use these other systems to compensate for the dysfunction in the semicircular canals. Therefore, balance problems associated with hearing loss usually diminish over time.
Syndromic hearing loss
Syndromic hearing loss is generally classified by the overall syndrome that leads to hearing impairment. Based on a database search conducted in 1995 for the National Institute on Deafness, there are at least 396 multi-symptom genetic syndromes in which hearing loss is indicated as a major feature. As a part of this work, Dr. G. Bradley Schaefer compiled a list of the top ten syndromes in terms of incidence and prevalence in the population. This list, in order of prevalence, is: hemifacial microsomia and related oculo-auriculo-vertebrali (OAV) spectrum disorders; Stickler syndrome; congenital cytomegalovirus (not genetic); Usher syndrome; branchiootorenal (BOR) syndrome; Pendred syndrome; CHARGE association; neurofibramatosis 2; mitochondrial disorders; and Waardenburg syndrome. Other syndromes of which hereditary hearing loss is a feature include: the oto-palatal-digital syndromes; the oral-facial-digital syndromes, skeletal dysplasias (particularly osteogenesis imperfecta); metabolic storage disorders (particularly mucopolysaccharidoses and Refsum disease); Townes-Brock syndrome; and Wildervank syndrome. Each syndrome within each group may be quite rare, but the combined number of individuals affected with hereditary hearing loss in each group of syndromes is significant.
Non-syndromic hearing loss
Non-syndromic hearing loss is generally classified by the age of onset, the degree of audiological impairment, the progressive or non-progressive nature of the impairment, and the mode of inheritance.
Otosclerosis is the most common form of non-syndromic progressive conductive hearing loss in adults. It is caused by a growth of the spongy bone tissue in the middle ear which prevents the ossicles (malleus, incus, stapes) from being able to move as well as they once did. In certain advanced cases of otosclerosis, there may also be damage to the auditory nerve (sensorineural hearing
Dominant progressive hearing loss (DPHL) and prebycusis (hearing loss related to aging) are the most common forms of non-syndromic progressive sensorineural hearing loss. DPHL tends to have an earlier age of onset than prebycusis, but this is highly variable between families. Within families, the age of onset of DPHL is generally fairly constant. The typical age of onset of DPHL is early childhood, but in some families it does not show symptoms until early or middle adulthood. Some individuals affected with DPHL also have problems with balance because of an alteration of the semicircular canal structures within their inner ears. These balance problems are not observed in other individuals with DPHL, suggesting that DPHL is caused by more than one gene or gene mutation. Prebycusis is not thought to be due to genetic causes. It is the most common form of hearing loss and everyone who lives beyond a certain age develops it to some degree. Prebycusis is thought to be caused by the combined effects of aging and the noises from the environment that a person has been exposed to. People who live, work, or entertain themselves in loud environments generally develop prebycusis to a greater degree than those people who exist in quieter surroundings.
As of early 2001, mutations in at least 70 separate genes have been determined to cause hereditary hearing loss. This number is expected to increase markedly as the genetic mutations causing the nearly 400 syndromes associated with hearing loss are identified.
Approximately 75-80% of non-syndromic hereditary hearing loss is due to mutations that are autosomal (non-X linked) recessive. Approximately 20% are due to autosomal dominant gene mutations. The rare remaining cases of non-syndromic hereditary hearing loss are attributed to X-linked disorders. Mutations in the mitochondrial DNA, which are just beginning to be understood, may contribute to many cases of hereditary hearing loss that have formerly been assigned to one of the above categories by inheritance patterns alone, not on the basis of knowledge of the involvement of a specific gene.
While most genetic data is carried on the chromosomes in the nucleus of the cell, there are also tiny chromosomes in the mitochondria of cells. The method of inheritance of mitochondrial abnormalities is nearly exclusively maternal (through the mother). The mitochondria that develop in a human are almost all produced by replication of the maternal mitochondria from the egg, or ovum. The sperm contains almost no mitochondria. The percentage of hereditary hearing loss due to abnormalities in mitochondrial DNA is not yet known. Hearing loss due to mitochondrial inheritance may be either syndromic or non-syndromic. Mitochondrial mutations are known to be the cause of at least some of the adult onset hearing loss seen in individuals also affected with diabetes mellitus.
Otosclerosis is inherited via an autosomal dominant mutation located at the terminal end of the q arm of chromosome 15 (15q26.1-qter). The inheritance characteristics of otosclerosis show reduced penetration. A dominant condition with complete penetrance should show symptoms of the gene mutation in all individuals possessing the mutation (100% penetrance). However, because of the age-related symptoms of otosclerosis, many individuals possessing the genetic mutation known to cause otosclerosis do not have any symptoms of the disease. Similarly, when obtaining a family history, it is very possible that individuals from previous generations died of other causes prior to showing any signs of being affected with otosclerosis.
DPHL is transmitted between generations via one of several autosomal (non X-linked) dominant genes called the DFNA genes. By early 2001, 18 genes had been identified as DFNA genes. Children of a parent with DPHL have a 50% chance of inheriting the altered gene and having hearing loss. If both parents have DPHL each child has a 75% chance of inheriting hearing loss. DFNA1 has been localized to chromosome 5, while DFNA3 has been localized to chromosome 13.
Deafness is estimated to affect 1.3 to 2.3 out of 1,000 children in the United States. Partial hearing loss is suspected to affect more than double that number. In adults, the incidence of some form of hearing loss is much higher than in children. As the population ages, the percentage of Americans affected with some type of hearing impairment is likely to climb.
It is estimated that approximately 10% of the population of the United States has partial hearing loss or deafness. This number is higher worldwide because non-genetic causes of hearing loss that are no longer as prevalent in the United States are still affecting individuals in many other parts of the world. These non-genetic causes of hearing impairment or loss include rubella, premature birth, meningitis, and incompatibility in the Rh blood factor between mother and fetus.
From studies of pupils at schools for the deaf in the United States, it is estimated that approximately 50% of
Otosclerosis is estimated to affect between 10% and 18% of all white and Hispanic women and between 7% and 9% of all white and Hispanic men. People of Asian descent are affected with otosclerosis at about half the rate seen in whites and Hispanics, with the same observed sex differences. In African-Americans, only about 1% of the total population is affected with otosclerosis, with minimal differences between males and females. Otosclerosis is exceedingly rare in people of Native American descent.
Accurate demographic figures on the rate of occurrence of DPHL were not available in early 2001. This is because past epidemiological studies of progressive hearing loss have failed to separate DPHL out from the other progressive sensorineural hearing losses.
Signs and symptoms
Syndromic types of hearing loss are generally characterized by the findings and symptoms additional to hearing loss that are associated with the particular syndrome.
Otosclerosis is characterized by an initial loss of hearing in the low frequencies, followed by a loss of the high frequencies, then a loss of the middle frequencies. It may rapidly advance through these stages in some affected individuals, while in others, it may stabilize for a period of years before progressively worsening. Many affected individuals have symptoms only in one ear at first, but otosclerosis almost inevitably will affect both ears. The maximum hearing loss due to otosclerosis without involvement of the auditory nerve is in the moderate range. As an affected person ages and the auditory nerve becomes involved, the hearing loss may progress to severe, or even profound, when this person reaches their 60s and 70s.
There are four main categories of DPHL: early-onset, high frequency, midfrequency, and low frequency. Early-onset types of DPHL tend to occur in early childhood and progress at varying rates to deafness. The other three types are categorized by the frequency range in which hearing loss first occurs.
Hearing is generally tested using earphones. Sounds are sent into the earphones at various decibel and frequency levels. This test allows the observer to determine the amount of hearing loss in decibels and the range of
Hearing loss is categorized by determining the hearing threshold of the affected person. The hearing threshold is the amount of sound that that individual can just barely hear. The hearing threshold of an individual is the hearing level (HL) of that person. It is measured in decibels (dB). A person with up to a 25 dB HL is categorized as having "normal" hearing. Mild hearing loss is defined as an HL in the 26 to 45 dB range. Moderate hearing loss is defined as an HL in the 46 to 65 dB range. Severe hearing loss is defined as an HL in the 66 to 85 dB range. Profound hearing loss is defined as an HL greater than 85 dB. The average person speaking English in a conversational tone tends to speak in the 30 to 60 dB range depending on the particular sounds being made. Persons with mild hearing loss will generally be able to hear and understand one-on-one conversations if they are close to the speaker. These individuals may have difficulty hearing a speaker who is far away, has a soft voice, or is surrounded by background noise. Persons with moderate hearing loss may have problems hearing conversational speech, even at relatively close range and in the absence of background noises. Persons with severe hearing loss have difficulty hearing in all situations. These people are not usually able to hear speech unless the speaker is talking loudly and is at relatively close range. Persons with profound hearing loss may not hear loud speech or environmental sounds. These people are unlikely to use hearing and speech as primary means of communication.
Hearing loss is also measured in terms of the frequency of the sounds that can or cannot be heard. Frequency is measured in hertz (Hz). The normal hearing range for humans is from approximately 100 Hz to 8,000 Hz. The normal frequency of the sounds of the English language fall between approximately 240 Hz and approximately 7,500 Hz. In individuals with progressive conductive hearing loss, it is generally the highest frequency range or the lowest frequency range that is lost first; the middle frequency range is generally lost last. In individuals affected with progressive sensorineural hearing loss, it may be any of the three frequency ranges that is lost first.
Hearing loss is generally plotted on a graph called an audiogram. This is a graph of frequency (in Hz) versus HL (in dB).
Syndromic hereditary hearing loss is differentially diagnosed by the presence of the non-hearing loss symptoms that the patient also possesses. Non-syndromic hereditary hearing loss is differentially diagnosed from syndromic by the absence of such other symptoms. Types of non-syndromic hereditary hearing loss are differentially diagnosed by the age of onset of the symptoms; the progressiveness, or non-progressiveness, of the hearing loss; the degree of symmetry of the hearing loss from one ear to the other; and the type of hearing loss: conductive, sensorineural, or mixed. Occasionally, a differential diagnosis also includes the inheritance pattern of the non-syndromic hearing loss. This inheritance pattern is generally determined by obtaining family medical history information on the affected person's family. Tests looking for specific gene changes in specific genes for certain non-syndromic hearing losses, including prenatal testing, are also beginning to become more available.
Treatment and management
Certain types of conductive hearing loss can be treated by surgery to correct the dysfunctional portion of the ear. Sensorineural hearing loss is generally not able to be repaired by surgery.
Most people with partial hearing loss can benefit from the use of hearing aids and/or sign language. Sign language and writing are often the primary forms of communication used by people suffering from severe, profound, or complete hearing loss.
The prognosis for individuals affected with hereditary hearing loss is largely dependent on the type of hearing loss experienced. In the absence of non-hearing loss related symptoms, the loss of hearing does not generally present any increased risk of illness and death. Hearing aids and/or the use of sign language can often improve the quality of life of those affected with a hereditary hearing loss.
Gorlin, Robert J., Helga V. Toriello, and M. Michael Cohen, Jr., eds. Hereditary Hearing Loss and Its Syndromes. Oxford: Oxford University Press, 1995.
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League for the Hard of Hearing. 71 West 23rd St., New York, NY 10010. (917) 305-7700 or (917) 305-7999. Fax: (917) 305-7888. <http://www.lhh.org/index.htm>.
National Association of the Deaf. 814 Thayer, Suite 250, Silver Spring, MD 20910-4500. (301) 587-1788. firstname.lastname@example.org. <http://www.nad.org>.
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Paul A. Johnson