Like many genetic disorders such as diabetes and epilepsy, deafness has a genetic predisposition. Deafness can occur at any time during the pre-birth, birth, and post-birth periods, and even age-related deafness is associated with genetic factors in individuals. Hereditary hearing impairment accounts for 60% of the prevalence of hearing impairment in children in developed countries, and is particularly significant in countries with high levels of consanguinity; many delayed hearing losses are also associated with their own genetic defects or are caused by genetic defects and polymorphisms that predispose patients to deafness-causing factors. However, in developing countries, hearing impairment due to infectious factors is more common, so the proportion of hereditary hearing impairment is relatively small (in China, hereditary deafness also accounts for 60%).
According to the projection of the second national sample survey of people with disabilities in 2006, the total number of people with all kinds of disabilities in China is 82.96 million, among which 27.8 million people have hearing disability, which is the first of all kinds of disabilities, and the number of newborn deaf children is increasing at the rate of about 20,000 or 30,000 every year, among which severe and very severe deafness accounts for about 80%, which shows that genetic factors are one of the most important factors leading to new deafness. The prevention of deafness caused by genetic factors should be the focus of deafness prevention and treatment for a period of time in the future.
1. How deafness is inherited
The material basis of human heredity is chromosomes, which are found in the nucleus of cells. There are 23 pairs of chromosomes, 22 of which are autosomes and one pair is sex-related, called sex chromosomes. Of these chromosomes, half come from the father and half from the mother. In other words, when parents transmit genetic information to their children, they first divide their chromosomes into two equal groups, and then pass them on to the next generation in a random combination of two, so that some of the parents’ characteristics are passed on to their children. If this is the case, why do some children born to congenitally deaf parents have no hearing impairment, while some parents with normal hearing give birth to deaf children? How can some families have several congenitally deaf children while others have only one deaf person in the family? The answer is that the difference in individual genetic background, i.e., the mode of inheritance, determines the difference in clinical appearance.
2. Mode of inheritance and characteristics of deafness
Seventy percent of hereditary deafness is non-syndromic deafness, i.e., no abnormalities other than hearing impairment; 30% of hereditary deafness is syndromic deafness, with multiple symptoms and signs other than hearing impairment, such as diseases of the skin system, eye disease, central nervous system, maxillofacial and/or skeletal system. In non-syndromic deafness, autosomal recessive mode of inheritance predominates, accounting for about 80%; autosomal dominant mode of inheritance accounts for about 20%, and sex-linked mode of inheritance and maternal mode of inheritance account for only 1% to 2%.
2. 1 Autosomal dominant deafness: In two sets of chromosomes, as long as one set has a deaf component, it will show deafness. We can then see some patterns ;
(1) If one of the parents is deaf, the probability of his or her child showing deafness is 50%; if both parents are deaf, the probability of the child showing deafness is 75%.
(2) The next generation of a deaf child may still be deaf, and the next generation of a non-deaf child will not develop hereditary deafness again.
(3) There is no gender difference in this hereditary deafness.
2. 2 Autosomal recessive hereditary deafness: deafness is expressed only when chromosomes from both parents contain deafness-causing information. If only one chromosome is faulty, the child does not develop deafness but becomes a carrier. Again, some patterns can be identified.
(1) If both parents are not deaf, but both are carriers, there is a 25% chance that their child will develop deafness, a 5O% chance that it will become a carrier, and a 25% chance that it will be completely normal. If one parent is deaf and the other is normal, neither child will become deaf, but both will be carriers. If both partners are deaf, the probability of their children becoming deaf is 100%, so it is important to avoid marriages between people with the same cause of deafness.
(2) If a deaf child marries a normal person, the next generation will not become deaf, but will be carriers. Whether the next generation of a child who is not deaf will develop deafness depends on whether he or she is a carrier, and also on the condition of his or her spouse, which means that the next generation of a child who is not deaf may also be deaf.
Among the many types of hereditary deafness, the chances of two people having the exact same deafness-causing gene are rare. Those of the same ancestry, on the other hand, have a much greater chance of being identical. Theoretically, cousins married to each other are 78 times more likely to have a congenitally deaf daughter than those who are not consanguineously married. And the incidence of genetic disease in the offspring of cousins married within three generations is 150 times higher than in the offspring of those who marry randomly. Consanguineous marriages can greatly increase the incidence of hereditary deafness.
3. Current status and significance of genetic testing technology
Due to the presence of environmental factors that cause prespeech deafness, it is sometimes impossible to determine whether a patient is genetically deaf, so routine screening and identification of common genetic mutations brings great help to genetic counseling.
3,1 Currently, several deafness focal genes have been identified in genetically deaf populations in the United States and Europe, and among them, GJB2 gene and PDS gene testing are listed as routine clinical tests by Harvard University Children’s Hospital and the University of Iowa Medical Center. In China, the GJB2 gene, PDS gene and mitochondrial DNA A1555G gene have been routinely tested for deafness by the Department of Otolaryngology and Head and Neck Surgery of the PLA General Hospital. Current research by scholars in China shows that deafness caused by mutations in the mitochondrial DNAA1555G gene, GJB2 gene, and PDS gene accounts for about 80% of the overall genetic deafness. Performing tests for these three genes can clarify the cause of most hereditary deafness.
3,2 Deafness gene testing also has the following implications.
(1) To guide the application of antibiotics (aminoglycosides): antibiotics are used for infection prevention and anti-inflammatory treatment. Aminoglycoside antibiotics such as gentamicin, streptomycin and butamycarbamycin are widely used in clinical practice because of their cheap price and good efficacy. The routes of administration include intravenous, intramuscular and topical. All antibiotics have certain side effects. Aminoglycoside antibiotics can cause deafness and nephrotoxicity. In some of these patients (mitochondria are extremely sensitive to the above-mentioned aminoglycosides, and deafness may occur after a small dose and short duration of application of these antibiotics, which is called “one shot to deafness”. It is essential to perform genetic testing for deafness before administering aminoglycoside antibiotics. In addition to clarifying the cause of deafness, it can also guide the administration of drugs to relatives of mothers who carry the mitochondrial gene mutation but do not develop the disease.
(2) Some deaf patients can be instructed to slow down the development of deafness: The large vestibular aqueduct syndrome is an autosomal recessive disorder caused by a mutation in the PDS gene. . This is the reason why mild head trauma may cause hearing loss in patients with large vestibular canals. Such patients should try to avoid head trauma and other causes of increased cranial pressure that can damage the inner ear, which may slow the development of deafness.
(3) The efficacy of cochlear implantation can be predicted: If the genetic diagnosis results suggest that congenital deafness is due to a mutation in the GJB2 gene or the PDS gene, then the auditory nerve and conduction pathway as well as the auditory speech center of this child should be normal and good results can be obtained with cochlear implantation.
(4) Patients and families with a confirmed diagnosis of hereditary deafness can be tested for genetic counseling. Evaluation of the chances of deafness in children born again.
As a new technology and method emerging in the field of otology, genetic diagnosis of deafness has several important features.
(1) The genetic diagnosis technique allows accurate molecular etiological analysis of a certain percentage of deafness patients, whereas previously the diagnosis of non-syndromic sensorineural deafness could only be made by history and exclusion methods to presume the etiology;
(2) Genetic diagnostic techniques can identify deafness susceptibility before symptoms and conventional audiometric or imaging techniques;
(3) Genetic diagnosis can be used as an adjunct and supplement to conventional audiometric or imaging techniques in some cases and can be used for remote diagnosis;
(4) Genetic diagnosis together with screening technology and prenatal diagnosis can reduce the occurrence of deafness, avoid the birth of deaf children, and effectively interrupt the transmission of hereditary deafness in deaf families.
4. Prevention of congenital inherited deafness should be the main focus.
4.1 Strictly enforce the marriage law and absolutely prohibit marriage between close relatives;
4.2 The re-birth of parents who have already had hereditary deaf children, because of its hereditary risk of 25% (recessive inheritance law), is a priority target for the prevention of birth of deaf patients;
4. 3 Young men and women who are deaf, to determine whether they have family heredity through deafness genetic counseling. Patients who are deaf due to the same genetic mutation (e.g. both spouses are deaf with GJB2 or both spouses are deaf with PDS mutation causing deafness in the large vestibular plumbing, 100% of their offspring will develop deafness), try to avoid marrying patients with the same genetic deafness; if one partner has identified the causative deafness genetic mutation, their spouse or subject shall undergo full sequence analysis of the corresponding gene for accurate genetic counseling and fertility guidance;
4.4 First- and second-degree relatives of patients with definite hereditary deafness have a 25-50% chance of being carriers of the deafness mutation in their families, and the re-birth of these relatives must be supervised by deafness genetic testing.
4,5 Mitochondrial DNA mutation deafness, as their maternal offspring will definitely carry their mother’s mutated mitochondrial gene, is a reason for them to become sensitive individuals to environmental factors, especially ototoxic drugs that cause deafness; in such families, continuous education and monitoring will be carried out, and there must be strict medication instructions for each of their medical visits, away from aminoglycosides.