Marie-Louise Barrenäs

Ear and hearing in relation to genotype and growth in Turner syndrome

Hearing loss, auricular anomalies and middle ear infections are common findings in many genetic disorders, but the mechanisms have remained unknown. We studied ear and hearing problems in Turners syndrome (TS) in relation to the degree of X chromosome loss (i.e. degree of mosaicism) and growth. One hundred and nineteen girls and women with TS were studied regarding audiometry, fluorescent in situ hybridisation, serum concentration of insulin-like growth factor-1 (IGF-1) and body height. It was found that sensorineural hearing loss and occurrence of auricular anomalies were significantly increased the greater the proportion of 45,X cells in a particular individual (P<0.05 and P<0.001, respectively). Middle ear infections and sensorineural hearing loss were negatively correlated with IGF-1 (P<0.05 and P<0.001, respectively). Hearing correlated positively with height (P<0.01) and IGF-1 independently of age (P<0.05). Height correlated positively with IGF-1 (P<0.001). Auricular malformations, middle ear infections and hearing impairment in TS were interpreted as due to growth disturbances during development. A new hypothesis on the pathophysiology of external, middle and inner ear disorders due to a delayed cell cycle caused by chromosomal aberrations per se and not only to the specific X chromosome deletion is presented.

Predictive Factors for the Severity of Tinnitus: Factores predictivos de la severidad del tinnitus

The majority of patients with tinnitus experience a lessening of their symptoms during an 18-month period after their first consultation. The exception to this rule is severe incapacitating tinnitus, the sometimes very troublesome symptoms of which show no sign of diminishing with time. The aim of the present study was to investigate risk factors for incapacitating tinnitus, as measured by absence from work related to tinnitus (AWT) of more than 1 month during an 18-month period after the first visit to the tinnitus clinic. Audiometric data and the scores from the Tinnitus Severity Questionnaire and the Nottingham Health Profile at the first visit to the clinic were correlated to AWT by a logistic regression model. By using this risk model, an individual risk score for AWT could be estimated. Depression and physical immobility were strong predictors of AWT, and hearing loss was moderate. Based on these results, we suggest that the aetiology of tinnitus severity could be described as depression-/anxiety-related, somatic, and auditory tinnitus.

Living with a male with noise-induced hearing loss: Experiences from the perspective of spouses

The aim of this inductive study was to describe, from the perspective of the spouses, their experiences of living close to a male with severe noise-induced hearing loss. An additional aim was to generate the first step of a theory of how these spouses managed their daily life. The study sample consisted of 10 strategically selected females who differed in age, educational status, number of children and years of marital relationship. Verbatim transcribed thematized interviews were analysed according to a method influenced by the constant comparative method for grounded theory. Two main variables, or core concepts, were identified: the husbands reluctance to acknowledge hearing difficulties and the impact of hearing loss on the intimate relationship. Combinations of these main variables were related to four qualitatively different strategies used by the spouses: co-acting, minimizing, mediating and distancing strategies. It is suggested that the type of strategy chosen by the spouse influences the outcome of the audiological rehabilitation.

Chromosomal mosaicism mitigates stigmata and cardiovascular risk factors in Turner syndrome.

Objective  To study genotype–phenotype correlations in Turner syndrome (TS) regarding body composition, cardiovascular risk factors, stigmata and age at diagnosis vs. degree of mosaicism estimated as the percentage of 45,X and 46,XX cells.

The influence of karyotype on the auricle, otitis media and hearing in Turner syndrome.

The study has investigated the relationship between the chromosomal aberration and ear and/or hearing disorders in 115 girls/women with Turner syndrome (TS). A dose-response relationship was found between the karyotype and hearing function. Hearing deteriorated more rapidly with increasing age in TS women lacking the whole p-arm of chromosome X (i.e. monosomy 45,X, or isochromosome cases 46,X,i(Xq)) as compared to women having a partial deletion of the p-arm (structural deletions or mosaicism cases), who, in turn, had poorer hearing than a female random population sample (46,XX) (P<0.001). Moreover, TS subjects having total deletion of the p-arm were three times more likely to have auricular anomalies or conductive hearing loss due to otitis media than subjects with partial deletion (P<0. 05). The results support the hypothesis that lack of growth-regulating genes such as the short stature homeobox-containing gene (SHOX), which is located within the pseudo-autosomal region on the p-arm of the X chromosome, may increase the occurrence of auricular malformations and otitis media and also induce an earlier loss of hearing function. Accordingly, the ear and hearing disorders in TS may be a result of growth disturbances of the auricle, the mastoid, the Eustachian tube and the organ of Corti during development. It is suggested that karyotype may be used as a predictor for future ear and hearing problems in TS.

Impact of Growth Hormone Therapy on Quality of Life in Adults with Turner Syndrome

CONTEXT GH and/or oxandrolone are used to promote growth in Turner syndrome (TS). OBJECTIVE The aim of this study was to compare quality of life (QoL) in TS women with controls and determine the impact of growth promoting therapy on QoL in TS women. DESIGN This was a cross-sectional, case-control study. SETTING The study was conducted at an outpatient clinic at Sahlgrenska University Hospital, Göteborg, Sweden. PATIENTS PATIENTS included 111 TS women (age range 18-59 yr) and 111 randomly selected, age-matched women (25-54 yr) from the World Health Organization Monitoring Trends and Determinants for Cardiovascular Disease project (Göteborg, Sweden) served as controls. MAIN OUTCOME MEASURES QoL was estimated by the Psychological General Well-Being scale (anxiety, depressed mood, positive well-being, self-control, general health and vitality) and the Nottingham Health Profile (physical mobility, pain, sleep, energy, social isolation, and emotional reactions). RESULTS TS women reported more social isolation than controls (P < 0.001). After age adjustment, significantly less pain (<0.05) was reported attributable to GH treatment within TS. No significant difference in any other subscales used could be shown. In TS, QoL was negatively affected by higher current age and age at diagnosis and positively affected by better body balance, fine motor function, and higher bone mineral density. CONCLUSIONS Social isolation was more commonly reported in the whole TS cohort than in the population. Except for less pain, no significant impact on QoL attributable to GH treatment could be found, despite the mean +5.1 cm final height.

The influence of eye colour on susceptibility to TTS in humans

In order to investigate the function of the inner ear melanin, noise-induced temporary hearing loss (temporary threshold shift, TTS) was studied in humans with either blue or brown iris colour. Sixty-eight normally hearing teenage boys participated in this study. Hearing thresholds before and after exposure were established with a computerized sweep frequency audiometer in the frequency range 0.8-8 kHz. The noise exposure consisted of a 1/3 octave band-filtered noise with centre frequency 2 kHz at 105 dB SPL for 10 min. The mean TTS in the frequency range 2-8 kHz showed a significant difference with the brown-eyed subjects developing least TTS, and the blue-eyed subjects most TTS.

Morbidity and mortality after childbirth in women with Turner karyotype

STUDY QUESTION Do women with Turner karyotype have increased mortality and morbidity in the years after childbirth? SUMMARY ANSWER No mortality occurred during pregnancy and follow-up in women with Turner karyotype, but a higher rate of circulatory and endocrine diseases and a high risk of aortic aneurysm were confirmed. WHAT IS KNOWN ALREADY Pregnancies in women with Turner karyotype are high-risk pregnancies with an increased risk of maternal mortality from aortic dissection and morbidity from hypertensive disorders. STUDY DESIGN, SIZE, DURATION A retrospective Swedish population-based registry study of 124 women with Turner karyotype born between 1957 and 1987 and who gave birth between 1973 and 2010. Women with Turner karyotype without childbirth (n = 378) were selected as controls. A second control group consisted of women from the Swedish Medical Birth Register (MBR) (n = 1230) matched for maternal age, number of children and year of birth of the first child. PARTICIPANTS/MATERIALS, SETTING AND METHODS Women with Turner karyotype were identified in the Swedish Genetic Turner Register. Data were obtained by using the unique personal identification number with cross linkage to the Swedish MBR, the Cause of Death Register, the National Patient Register and the Swedish Cancer Register. Hazard ratio (HR) with 95% confidence interval (CI) was used in the analysis of morbidity. MAIN RESULTS AND THE ROLE OF CHANCE No mortality occurred in women with Turner karyotype and childbirth. Diseases of the circulatory system occurred more often in women with Turner syndrome under the age of 40 years compared with the MBR control group (HR 4.59; 95% CI 2.75-7.66) but was similar at or above the age of 40 years. Morbidity from circulatory diseases was increased before pregnancy (HR 3.83; 95% CI 1.02-14.43) and during pregnancy or within 1 year after (HR 5.78; 95% CI 1.94-17.24), but was similar after 1 or more years after delivery (HR 1.91; 95% CI 0.74-4.96). Aortic aneurysm occurred in 11/502 (2.2%) women with Turner karyotype and in three women (2.4%) during pregnancy. The long-term follow-up showed that aortic dissection was a common cause of death in young women with Turner karyotype without childbirth. A thorough cardiac evaluation before pregnancy in women with Turner karyotype is of utmost importance. LIMITATIONS, REASONS FOR CAUTION Although this was a population-based registry study performed over a period of more than 20 years, a much longer follow-up and larger series are needed to assess rare events. The study also lacks information on phenotype and mode of conception in women with Turner karyotype. Women who gave birth probably represent a selection of healthier women with Turner karyotype. WIDER IMPLICATIONS OF THE FINDINGS The high risk of aortic aneurysm in young women with Turner karyotype is in agreement with the literature.

Tinnitus in the general population with a focus on noise and stress: a public health study.

Objectives: To evaluate the influence of noise and stress on the probability of tinnitus in the general population. Design: Questionnaire data were obtained from 12,166 subjects. Results: Each year of age increased the odds ratio of tinnitus by about 3%. Men generally showed a higher risk for tinnitus compared with women. Exposure to noise and stress emerged important for the probability of tinnitus. However, for the transition from mild to severe tinnitus, stress turned out to be especially important. Conclusions: Stress management strategies should be included in hearing conservation programs, especially for individuals with mild tinnitus who report a high stress load.

The association between short stature and sensorineural hearing loss.

In order to test the Thrifty Phenotype Hypothesis on hearing, data from two cross-sectional studies on hearing were re-evaluated. The data sets comprised 500 18-year-old conscripts, and 483 noise-exposed male employees. Sensorineural hearing loss (SNHL) was over-represented among conscripts with a short stature (odds ratio=2.2) or hearing loss in the family (odds ration=4.2), but not among noise-exposed conscripts (odds ratio=0.9-1.3). Among noise-exposed short employees, hypertension and age exhibited a negative impact on high frequency hearing thresholds, while among tall employees hypertension had no effect on hearing and the influence of age was less pronounced (p<0.01 for body height; p<0.02 for age, hypertension and the interaction between body height and hypertension; p<0.05 for the interaction between body height and age). This suggests that mechanisms linked to fetal programming and growth retardation and/or insulin-like growth factor 1 levels during fetal life, such as a delayed cell cycle during the time window when the cochlea develops, may cause SNHL in adulthood.