Hereditary hearing loss is one of the forms of congenital hearing impairment caused by genetic mutations and for this reason can be inherited from parents to offspring. Symptoms of this condition are hearing loss of varying severity, often occurring in the first months and years of a child’s life (very rarely after 6 years), as well as secondary speech disorders. Diagnosis is carried out on the basis of audiometric studies (audiometer, sound test), hereditary history of the patient and molecular genetic analysis. There is no specific treatment, patients often require training in specialized centers and rehabilitation.
Hereditary hearing loss is a broad group of various genetic diseases that are accompanied by hearing loss up to complete deafness (depending on the form of pathology). These diseases account for more than half of the cases of early hearing loss – the remaining variants are the result of prenatal damage to the fetus or acquired hearing loss in early childhood. Such conditions have been known for a very long time. They were actively studied by otolaryngologists, neurologists, and in the XX century by geneticists who were able to determine the hereditary nature of some of these diseases.
It was also found that some varieties are found in combination with other symptoms of a genetic disease (syndromic forms), and other types are manifested only by hearing disorders (non-syndromic forms). Further studies have shown the presence of a huge number of varieties of the disease, which required the creation of a complex classification of this condition depending on its type, the mechanism of damage to the hearing organ, the type of inheritance and other factors. Hereditary hearing loss is a fairly common pathology – according to some data, its occurrence is 1-2 cases per 1000 newborns.
Causes and classification
All forms of hereditary hearing loss are divided according to the following characteristics: combination with other disorders within the same genetic pathology (syndromic and non-syndromic forms), the mechanism of transmission to offspring (autosomal dominant, autosomal recessive and X-linked), the cause of hearing impairment (conductive, sensorineural and mixed hearing loss). In addition, clinicians divide all cases of the disease according to the degree of hearing impairment (mild, moderate, moderate-severe and deep) and the age of occurrence of speech development disorders (prelingual and postlingual). The complexity of classifying all forms is due to the fact that this condition can be the result of a huge number of different genetic mutations, which, moreover, can lead to unequal phenotypic manifestations of pathology.
Non–syndromic forms are the most common variants of this condition – in various populations they account for 60 to 80% of all cases of congenital hearing disorders that are inherited. Usually (about 75-80%) these are autosomal recessive pathologies caused by a mutation of the GJB2 gene located on chromosome 13. The gene encodes a protein called connectin-26, which is involved in the formation of intercellular connections in the sensorineural apparatus of the inner ear. As a result of mutation in homozygotes, this protein is not formed at all or contains a certain defect. This becomes the cause of pronounced (most often deep) prelingual hereditary hearing loss of a sensorineural nature. Other genes that give a similar clinical picture have not yet been thoroughly studied.
Dominant forms of nonsyndromic hereditary hearing loss are almost always allelic variants of other genetic diseases, which, among other things, are characterized by hearing disorders. They account for approximately 20% of all cases of non-syndromic hearing aid lesions. Thus, one of the forms of dominant hereditary hearing loss (DFNB18) is caused by a mutation of the USH1C gene located on the 11th chromosome. The expression product of this gene is the PZD protein, which is actively involved in the formation of hair cells and other components of the inner ear. The USH1C mutation is also responsible for some variants of Usher syndrome (type 1C).
Dominant nonsyndromic hereditary hearing loss of type DFNB12 is caused by a defect in the CDH23 gene localized on the 10th chromosome. It encodes one of the main proteins-cadherins, which are involved in the formation of many neurostructures and sensory organs, so CDH23 mutations are manifested not only by hearing disorders, but also by Usher syndrome 1D, retinopathy pigmentosa and other similar conditions. Similarly, allelic diseases are dominant hereditary hearing loss DFNB4 and Pendred syndrome caused by a mutation of the SLC26A4 gene located on the 7th chromosome. The expression product of this gene is one of the transmembrane anion channels called pendrin, most commonly found in the hearing organ, thyroid gland and some other organs. Most dominant forms of hereditary hearing loss develop after the formation of speech in a child.
Much rarer (about 1-3% of all cases) are forms with an X-linked inheritance mechanism. The most common variant of this pathology is mutations of the POU3F4 gene, which encodes an important transcription factor necessary for the expression of other proteins (not thoroughly studied) involved in the formation of hearing organs. The violation of the functioning of this sense organ in this case has a conductive character and is caused by abnormal circulation of the perilymph. Mutations of the PRPS1 gene, which encodes the sequence of one of the enzymes (phosphoribosyl pyrophosphate synthetase-1), can also lead to X-linked hereditary hearing loss – the pathogenesis of the development of hearing disorders remains unclear. The rarest described form of hereditary hearing loss is mutations of the MTRNR1 gene, which is localized not in the cell nucleus, but in mitochondrial DNA – for this reason, the disease is transmitted only through the female line or from the mother to children.
The main manifestation of hereditary hearing loss, as can be understood from the name of the pathology, is hearing loss of varying severity and character. Symptoms of the disease often appear in early childhood (prelingual development), while eventually speech development may suffer – there is a direct correlation between the degree of hearing loss and the delay or underdevelopment of the speech apparatus. Such an early occurrence of hereditary hearing loss may indicate the autosomal recessive nature of this pathology. Gradual postlingual hearing loss (after 6-8 years) most often has an autosomal dominant nature of inheritance. When conducting audiography, it is possible to determine the degree of hereditary hearing loss, as well as its frequency (the sounds of which frequency the patient perceives the weakest). In some cases, hearing loss may occur in adulthood.
In addition to hearing loss itself, various forms of hereditary hearing loss can manifest other symptoms. The most frequent of them is the dysfunction of the vestibular apparatus, due to the anatomical and functional proximity of the organs of hearing and balance. In addition, there may be signs of other genetic and congenital malformations: disorders of the thyroid gland, skin (hyperkeratosis, psoriasis), urinary system, visual organs. This is most characteristic of the syndromic forms of hereditary hearing loss: Waardenburg disease, Stickler disease, Usher’s disease, Pendred’s disease and a number of others. In total, more than 400 genetic pathologies have been described, which can manifest as hereditary hearing loss syndrome.
Diagnosis and treatment
To determine hereditary hearing loss, traditional otolaryngological techniques are used: audiometry, examination of the auditory passages, the response of the auditory part of the brain stem (the so-called BAYER technique), induced otoacoustic emission. Since in most cases this pathology is determined in childhood, audiometry is often performed in a playful way. With hereditary hearing loss of different types, both a violation of the air conduction of sound vibrations (especially with conductive mechanisms of the development of the disease) and a combined decrease in bone and air conduction can be determined. A certain role in the diagnosis of pathology can be played by anomalies in the development of hearing organs – for example, a wide whirlpool of the vestibule in non-syndromic hereditary hearing loss type 4 (DFNB4) or Pendred syndrome.
Hearing loss can be observed both in relation to certain sound frequencies and in a wide range of vibrations. The severity of the disorders also varies quite a lot with various forms of hereditary hearing loss. With the sensorineural mechanism of the lesion, there will be a decrease in the activity of impulses in the auditory nerve, which is determined during electrophysiological studies. Delayed speech development is found in prelingual forms of hereditary hearing loss. For a number of types of the disease (for example, caused by mutations of the genes GJB2, SLC26A4, POU3F4), methods of modern genetics are used as diagnostics – sequencing of the gene sequence to detect mutations.
Treatment of hereditary hearing loss, as a rule, boils down to the selection of hearing aids of various types, which should be used as early as possible to prevent the pathology of speech development. In some cases, with isolated conductive lesions of the hearing organs, surgical correction can be performed, but its results are ambiguous. Most forms of hereditary hearing loss rarely progress to absolute deafness, so lifelong use of hearing aids provides an acceptable quality of life for the patient.
Prognosis and prevention
The prognosis of hereditary hearing loss regarding recovery is unfavorable – in most cases, hearing loss persists throughout life. Extremely slow progression of symptoms or even lack of progression allows the use of hearing aids. In cases where prelingual hearing loss was detected late in the child, correction of speech defects by a speech therapist may be required. For a number of syndromic forms of hereditary hearing loss in children, the prognosis largely depends on concomitant disorders and malformations. To prevent this condition, methods of genetic prenatal diagnosis are used, as well as the identification of the carriage of defective genes (with recessive and X-linked types of the disease), followed by medical and genetic counseling of parents before conception.