Ear and hearing problems in Turner syndrome

Abstract

Turner Syndrome is a common chromosomal disorder and affects approximately one in every 2000 newborn girl. The syndrome is defined as a total (45,X) or partial loss of the second sex chromosome in combination with the typical characteristic features, which are short stature (less than 150 cm), absent estrogen production due to ovarian dysgenesis, with failure to enter puberty spontaneously and infertility. Among other associated anomalies ear and hearing problems are common, involving both the middle and inner ear. In childhood repeated attacks of acute otitis media and serous otitis media are frequent, sometimes leading to chronic middle ear diseases. Also a sensorineural hearing loss is common, usually described as a typical dip in the mid-frequencies. Later in life, an early aging is seen, with a progressive sensorineural high frequency hearing loss (presbyacusis). When added to the dip, it results in a rapid onset of social hearing impairment, often requiring hearing aid use. The cause of the related hearing problems is not known.

Children with Turner syndrome were examined otologically and audiometrically. Also immunomarkers and autoantibodies were investigated. A high incidence of recurrent otitis media was found with eardrum pathology and conductive hearing loss as frequent sequelae. An immunodeficiency could not explain the repeated attacks of otitis media. The audiometric data confirm that the dip is progressing over time and show that the dip may be present as early as at the age of six, making it possible to predict a future hearing loss early. It is therefore important to have an early audiometric evaluation of every girl with Turner syndrome, including the testing of both air and bone conduction with absolute values, in order to discover the dip. In addition, a questionnaire, elucidating the influence of the hearing impairment on everyday life in 113 girls and women with Turner syndrome, was evaluated. The need for initiation of rehabilitative intervention is apparent, when the patient first begins to notice difficulty, as the hearing problems develop rather rapidly, leading to communication problems and tiredness due to intensive listening. Moreover it is established that the hearing problems are perceived as one of the most important problems associated with Turner syndrome.

An animal model, the Turner mouse, lacking the X-chromosome was investigated. The inner ear morphology was examined using light microscopy (agar and paraffin sections and phalloidin stained surface preparations), transmission- and scanning electron microscopy. The hearing was tested using auditory brainstem response and distortion product otoacoustic emissions. The "Turner mouse" appears to have ear and hearing problems quite similar to humans with Turner syndrome and can therefore be used in the future as a model to determine the auditory pathology underlying the syndrome. The results indicate that hearing problems in the "Turner mouse" are of cochlear origin, with an eight-nerve component.

Furthermore, to examine whether one of the reasons for the early presbyacusis in Turner syndrome can be due to the defect endogenous estrogen production, mapping of estrogen receptors in the inner ear was accomplished. Paraffin embedded inner ear sections from mouse, rat and human, both adult and fetal (normal and affected with Turner syndrome), were immunostained with antibodies against estrogen receptors a and b. For the first time estrogen receptors are shown to be present in the inner ear at specific locations important for hearing functions and inner ear homeostasis, implying that estrogens may have an effect on the hearing. If the lack of estrogens are important for development of presbyacusis in the normal population and patients with Turner syndrome can only be speculated upon. Maybe estrogens have certain protective effects.