Context: The phenotype in Turner syndrome (TS) is variable even in patients with a supposedly non-mosaic karyotype. Previous work suggested that there were X-linked parent-of-origin effects on the phenotype.

Hypothesis: TS phenotype is influenced by the parental origin of the missed X chromosome.

Design: Multicenter prospective study of TS patients and both their parents, determining parental origin of the X-chromosome, and characterizing the clinical phenotype.

Patients and methods: Eighty three TS patients and their parents. Inclusion criteria were TS with karyotype 45,X or 46Xi(Xq). Four highly polymorphic microsatellite markers on the X-chromosome DMD49, DYSII, DXS1283 and the androgen receptor gene, and three Y chromosome markers SRY, DYZ1, and DYZ3.

Outcome measures: The study determined the correlation between the parental origin of the X chromosome and the unique phenotypic traits of Turners syndrome including congenital malformations, anthropometry and growth pattern, skeletal defects, endocrine traits, education and vocation.

Results: An 83% of 45,X retained their maternal X (X^m), whereas 64% 46Xi(Xq) retained their paternal X^p (P < 0.001). Kidney malformations were exclusively found in X^m patients (P = 0.030). The X^m group had lower total and LDL cholesterol (P < 0.05higher BMI SDS (P = 0.03). that was not maintained after hGH treatment. Response to GH therapy was comparable. Ocular abnormalities were more common in the X^p group (P = 0.017), who also had higher academic achievement.

Conclusions: The parental origin of the missing short arm of the X- chromosome has an impact on overweight, kidney, eye and lipids, which suggests a potential effect of an as yet undetermined X chromosome gene imprinting.