ESPE Abstracts (2018) 89 P-P1-159

Does X-Chromosome Gene Dosage Determine Growth and Phenotypic Features in Turner Syndrome with 45,X/46,XX Mosaicism on Standard Karyotyping? A Cross-Sectional Analysis of the French National Rare Disease Network Database

Elodie Fiota, Delphine Zénatya, Paul Pickb, Patricia Boizeaub, Jeremy Haignereb, Sophie Dos Santosa, Sophie Christin-Maitrec, Jean-Claude Carela, Juliane Légera & French Turner Syndrome Study Groupd


aPaediatric Endocrinology and Diabetology Department, Reference Centre for Endocrine Growth and Development Diseases, Robert Debre University Hospital, Paris, France; bClinical Epidemiology Unit, Robert Debré University Hospital, Paris, France; cEndocrinology Department, Reference Centre for Endocrine Growth and Development Diseases, Saint-Antoine University Hospital, Paris, France; dReference Centre for Endocrine Growth and Development Diseases, Paris, France


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.

Table 1
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 malformation11%13%9%
Congenital kidney malformation0%11%22%**
Median age (y) before GH treatment119.89.6
Height deficit (SDS) with respect to target height before GH treatment1.44 (0.89; 2.37)2.08 (1.40; 2.39)2.33 (1.52; 2.89)
Spontaneous onset of puberty17%15%16%
Median age (y) at last evaluation13.616.416.0
Hearing impairment10%21%28%
Hashimoto thyroiditis7%20%33%
Overweight/obese7%10%23%*
*P<0.03; **P<0.01.

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.