More than 24,000 children are born with hearing loss in the United States each year. Boys Town National Research Hospital is a national leader in the diagnosis and treatment of children with moderate to profound hearing loss.
Information on Hearing Loss - Genetics and Deafness -
X-Linked Hearing Loss and Perilymphatic Gusher
X-linked hearing loss with perilymphatic gusher during stapes surgery is a complex but medically descriptive name for a genetic deafness syndrome. X-linked refers to the pattern of inheritance. This particular hearing loss has both sensorineural and conductive components with the conductive portion due to immobility of the stapes, one of the bones in the middle ear. Perilymphatic gusher during stapes surgery refers to a complication that occurs during surgery performed in an attempt to improve hearing.
X-linked Inheritance
X-linked refers to genes on the X chromosome. There are hundreds to thousands of genes on each chromosome and there are 23 pairs of chromosomes. One pair of chromosomes is called the set of sex chromosomes because they carry among others, the genes that provide the instructions for development of sexual characteristics. There are two sex chromosomes, the X and the Y. Females have a matched pair of X chromosomes with both having the same number and order of genes but not necessarily the same message on each gene in any given pair. Males have a mismatched pair with one X and one Y chromosome. The Y chromosome is smaller and does not have the same genes as the X, therefore the genes on the male's X come in only one copy. The genes on the sex chromosomes can be dominant or recessive just as the genes on the other twenty-two pairs of chromosomes, but a recessive gene on a male's X chromosome always will be expressed since he does not have a dominant gene to counteract it.
Most X-linked hearing loss genes are recessive. A woman with an X-linked hearing loss gene will most likely have a dominant gene for hearing on her other X chromosome and be a carrier. A carrier has a fifty-fifty chance of passing on the hearing loss gene. If a son receives the hearing loss gene, he will have a hearing loss because he has only one X chromosome. There will be no dominant gene for normal hearing on his Y chromosome. However, if a daughter receives the hearing loss gene, she most likely will have a dominant normal gene on her other X chromosome from her father and be a carrier like her mother. A male with an X-linked hearing loss cannot pass it on to his son because he will give his son a Y chromosome rather than an X. However all of his daughters will be carriers because he has only one X to pass to them and it has the gene for the hearing loss.
Hearing Loss
The hearing loss in males associated with the X-linked hearing loss with perilymphatic gusher during stapes surgery syndrome is a severe, mixed hearing loss which seems to be present at birth but becomes progressively worse(1). The conductive component of this loss results from immobility of the stapes, one of the tiny bones (ossicles) in the middle ear.
Usually, sound is received by the outer ear and passes through the ear canal, causing vibration of the ear drum or tympanic membrane. The malleus, which is pressed against the back side of the tympanic membrane, is the first of three tiny bones (ossicular chain) in the middle ear. The other bones in the ossicular chain are the incus and the stapes. Vibration of the tympanic membrane causes movement of the malleus. This is passed along the ossicular chain causing pressure on the stapes footplate and into the perilymph fluid behind the oval window. This causes a wave in the perilymph fluid which travels through the cochlea, where the mechanical energy is transformed to electrical energy that travels along the auditory nerve to the brain.
The immobilization of the stapes in this X-linked hearing loss is thought to be due to a higher than normal pressure of the perilymphatic fluid behind the oval window. The pressure interferes with movement of the stapes footplate and, thus, the transmission of sound waves.
About half of carrier females who have been studied have a mild mixed, or purely sensorneural hearing loss(2). The females with hearing loss have normal vestibular responses. Males also have an absent or strongly reduced vestibular response.
Genetic Mapping
Researchers have determined that the gene for X-linked hearing loss with perilymphatic gusher during stapes surgery is located in region 21 of the long arm of the X chromosome(3).
Because of the inheritance pattern of this syndrome, it was obvious to the geneticists that the gene had to be on the X chromosome. The geneticists were assisted in determining which part of the chromosome carries the gene by families who have males with a group of findings including choroideremia (an eye condition), hearing loss with perilymphatic gusher during stapes surgery, and mental retardation(4). Since choroideremia was known to be caused by an X-linked gene, it was postulated that these males might be missing part of the X chromosome which normally would include the genes needed for normal hearing and vision. Indeed, the chromosome (cytogenetic) testing of the affected males and the carrier females in these families revealed a small part of the X chromosome was missing in the carriers and the affected males. This information narrowed down the area of the X chromosome that needed to be studied with DNA testing in the attempt to find the gene itself.
Stapes Surgery
Most conductive hearing losses due to immobility of the footplate are due to a bony abnormality of the stapes which is called stapes fixation. This can be alleviated by surgically removing part or all of the stapes and replacing it with a prosthesis. Surgery has been performed on the stapes of some individuals with this X-linked hearing loss in an attempt to increase the mobility of the footplate.
However, in these cases, there is also an abnormality of the cochlea resulting in a small space through which the fluid around the brain can pass into the inner ear adding increasing the pressure of the perilymph fluid. The increased pressure of the perilymph fluid behind the oval window causes the fluid to gush out when even a pin size hole is made in the footplate. This can be a serious complication putting the individual at high risk for losing more or even all of their residual hearing in the affected ear, and also at risk for the development of meningitis.
References
Cremers, C.W.R.J., et al. (1985). X-linked progressive mixed deafness with perilymphatic gusher during stapes surgery. Archives of Otolaryngology 111: 249-254.
Cremers, C.W.R.J. & Huygen, P.L.M. (1983). Clinical features of the female heterozygote in the X-linked mixed deafness syndrome (with perilymphatic gusher during stapes surgery). International Journal of Pediatric Otorhinolaryngology 6: 179-185.
Brunner, H.G., et al. (1988). The gene for X-linked mixed deafness with perilymphatic gusher during stapes surgery (DFN3) is linked to PGK. Human Genetics 80: 337-340.
Nussbaum, R.L., et al. (1987). Isolation of anonymous DNA sequences from within a submicroscopic chromosomal deletion in a patient with choroideremia, deafness, and mental retardation. Proceedings of the National Academy of Sciences USA 84: 6521-6525.
Phelps, P. D., et al. (1991). X-linked deafness, stapes gushers and a distinctive defect of the inner ear. Neuroradiology 33: 326-330.
Date Originally Created: Spring of 1991
The information presented here first appeared in publications of the Boys Town National Research Register for Hereditary Hearing Loss, the National Institute on Deafness and Other Communication Disorders (NIDCD), Hereditary Hearing Impairment Resource Registry (HHIRR), or the Boys Town Research Registry for Hereditary Hearing Loss.
The Boys Town Research Registry for Hereditary Hearing Loss
The Boys Town Research Registry for Hereditary Hearing Loss (Registry) is designed to foster a partnership between families, clinicians and researchers in the area of hereditary hearing loss/deafness through three primary functions. First, the Registry disseminates information to professionals and families about clinical and research issues related to hereditary deafness/hearing loss. Second, the Registry collects information from individuals interested in supporting and participating in research projects. This information is used to support the third function of the Registry - matching families with collaborating research projects.
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