Risk analyses for the cognitive phenotype in Turner's syndrome: evidence of familial influence as a decisive factor.

The interindividual varying cognitive performance in female patients with Turner's syndrome has usually been attributed to the interindividual varying mosaicism with a consecutive variable loss of X-chromosome DNA or to secondary risk factors such as estrogen deficiency owing to ovarian failure. The aim of our study was to determine the specific impact of X chromosome-related features and associated risk factors, on the one hand and familial influences, on the other hand on the interindividual variation in the cognitive phenotype. One hundred and one subjects with Turner's syndrome and 53 sisters as controls for familial influences were examined by comparing the cognitive information processing abilities (Kaufmann Assessment Battery for Children [K-ABC]). Subjects with Turner's syndrome performed at a significantly lower level than sisters on all subscales (eg, Mental Processing Composite: Turner's syndrome 86.4 [SD 15.0] versus sisters 99.3 [SD 10.6]; P < .001). For the neurocognitive phenotype in subjects with Turner's syndrome, a significant correlation was found only with the sisters' cognitive abilities (Mental Processing Composite: r = .38, P < .05). In contrast, neither the individual mosaic status nor the known associated risk factors predicted the neurocognitive phenotype in Turner's syndrome. These results are corroborated in the regression analyses in those subjects with Turner's syndrome with a sister (Simultaneous Processing(sister) for Simultaneous Processing(Turner's syndrome): beta = .346, P < .05, corrected R2 = .049; and Mental Processing Composite(sister) for Mental Processing Composite(Turner's syndrome): beta = .354, P < .05, corrected R2 = .033). The interindividual variation of intellectual abilities in Turner's syndrome seems to be primarily related to familial coinfluences and not to the interindividual varying loss of X-chromosome DNA in terms of hidden mosaicism or potential associated risk factors.

Familial factors and hearing impairment modulate the neuromotor phenotype in Turner syndrome.

In Turner syndrome (TS), an X-chromosomal anomaly characterised by total or partial loss of the second X-chromosome, muscle hypotonia, and lower proficiency in fine and gross motor skills have been described. It is assumed that the neuromotor phenotype in TS is linked with X-chromosomal factors (individual mosaicism) and with the oestrogen deficiency due to streak gonads. From studies in normal populations, a further risk factor may be recurrent otitis media (OM), which occurs frequently in TS, often in combination with hearing impairment (HI). It is also likely that familial factors are involved. The aim of our study was to specify the respective impact of the interindividual varying status of mosaicism and of hypergonadotropic hypogonadism as well as of the risk factors recurrent OM and HI in comparison to familial coinfluences on the neuromotor proficiency (MOP) in TS. We used the Bruininks-Oseretsky Test of Motor Proficiency to examine 105 subjects with TS (mean age 9.4 years; SD 3.3 years) and 52 sisters (mean age 9.8 years; SD 3.7 years). Significant correlations were found for familial covariance regarding the relation between TS subjects and their sisters ( r=0.42, P<0.01) and HI and MOP ( r=-0.39, P<0.01) CONCLUSION: we conclude that the familial influences and risk factors such as recurrent otitis media in combination with hearing impairment serve primarily as important predictors of the individual neuromotor phenotype in Turner syndrome.