Background: Turner Syndrome (TS) with a 45,X phenotype is generally more severe than TS with mosaicism, but the potential role of the degree of mosaicism in modulating TS phenotype has never been investigated. We assessed the impact of various degrees of 45,X/ 46,XX mosaicism on phenotypic features in a cohort of TS patients.
Method: We analysed a cohort of TS with 45,X/ 46,XX mosaicism (percentage mosaicism from peripheral blood lymphocytes, known in n=183/221 cases), in a national observational multicentre study (n=1536). Data were collected retrospectively from medical records and analysed according to the degree of mosaicism, classified as low (<10%), moderate (10-30%) or high (>30%). The genetic analyses carried out included standard karyotype analyses of more than 20 cells or fluorescence in situ hybridization on about 100 cells.
Results: A trend towards association with the degree of mosaicism was observed for birth weight SDS, birth length SDS and height deficit with respect to target height SDS before growth hormone treatment, the patients with lower levels of mosaicism being less likely to be affected. High levels of mosaicism were associated with a higher frequency of malformations of the kidneys (P<0.01) but not of the heart. During adolescence, mosaicism levels were higher in patients who were overweight/obese (P<0.03), and hearing impairment and Hashimoto thyroiditis were more frequent in patients with higher levels of mosaicism. Spontaneous puberty was not associated with the degree of mosaicism.
|Patients 45,X/46,XX patients (n=183)|
|45X <10% (n=28)||45X: 10-30% (n=72)||45X ≥ 31% (n=83)|
|Birth weight (SDS)||−0.42 (−0.96; 0.56)||−0.51 (−1.12; 0.12)||−0.77 (−1.65; 0.11)|
|Birth length (SDS)||−0.42 (−1.49; 0.43)||−0.72 (−1.38; 0.22)||−0.93 (−1.75; −0.14)|
|Congenital heart malformation||11%||13%||9%|
|Congenital kidney malformation||0%||11%||22%**|
|Median age (y) before GH treatment||11||9.8||9.6|
|Height deficit (SDS) with respect to target height before GH treatment||1.44 (0.89; 2.37)||2.08 (1.40; 2.39)||2.33 (1.52; 2.89)|
|Spontaneous onset of puberty||17%||15%||16%|
|Median age (y) at last evaluation||13.6||16.4||16.0|
Conclusions: In TS patients with 45,X/ 46,XX mosaicism, high levels of mosaicism seem to be associated with a more severe phenotype. Further studies of larger cohorts are required to improve our understanding of these associations.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology