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Purpose: Turner syndrome is a developmental disorder caused by partial or complete monosomy for the X chromosome in 1 in 2,500 females. We hypothesized that single-nucleotide polymorphism (SNP) array genotyping could provide superior resolution in comparison to metaphase karyotype analysis to facilitate genotype-phenotype correlations., Methods: We genotyped 187 Turner syndrome patients with 733,000 SNP marker arrays. All cases met diagnostic criteria for Turner syndrome based on karyotypes (60%) or characteristic physical features. The SNP array results confirmed the diagnosis of Turner syndrome in 100% of cases., Results: We identified a single X chromosome (45,X) in 113 cases. In 58 additional cases (31%), other mosaic cell lines were present, including isochromosomes (16%), rings (5%), and Xp deletions (8%). The remaining cases were mosaic for monosomy X and normal male or female cell lines. Array-based models of X chromosome structure were compatible with karyotypes in 104 of 116 comparable cases (90%). We found that the SNP array data did not detect X-autosome translocations (three cases) but did identify two derivative Y chromosomes and 13 large copy-number variants that were not detected by karyotyping., Conclusion: Our study is the first systematic comparison between the two methods and supports the utility of SNP array genotyping to address clinical and research questions in Turner syndrome.

This review highlights recent developments in the detection and management of congenital heart disease and osteoporosis in patients with monosomy X, or Turner syndrome (TS). Magnetic resonance angiography (MRA) using gadolinium as a contrast agent demonstrates a higher prevalence and greater diversity of congenital cardiovascular defects than previously recognized in TS. Almost 50% of girls and women with TS have marked tortuosity or ectasia of the aortic arch, suggesting that these individuals may be at greater risk for aneurysm formation or dissection and therefore require closer monitoring. MRA also reveals that major venous anomalies are common in TS, with partial anomalous pulmonary venous return and persistent left superior vena cava each found in about 13% of patients. MR imaging even without contrast is a valuable complement to routine cardiac ultrasound in detecting abnormalities of the aortic valve. Abnormal electrocardiographic findings, including prolongation of the QTc interval, have recently been documented in many individuals with TS. Conduction and repolarization abnormalities have not been associated with congenital anatomic defects and are as common in young girls as adults. The clinical significance of these electrophysiological findings is unknown at present, but attention to the ECG in TS is important, particularly in monitoring the QTc when prescribing drugs associated with QT prolongation. Patients with TS are at high risk for osteoporosis as a result of premature ovarian failure and intrinsic bone abnormalities specific to the syndrome. Low cortical bone mineral density (BMD) is apparent in prepubertal girls, and it remains low in adults, independent of estrogen treatment and other hormonal factors. The low mineralization of cortical bone in TS may be associated with a small increased fracture risk, but no treatments are known to increase cortical bone mineral content in TS. Trabecular BMD is normal in TS women who have received continuous estrogen treatment from their mid-teens, although areal densitometry scores may be misleadingly low in very small patients. However, young women with ovarian failure who have not received estrogen treatment for extended periods of time are at high risk for osteoporosis of trabecular bone of the spine, with associated compression fractures and height loss. Therefore, judicious management of estrogen therapy to prevent osteoporosis while minimizing estrogen-associated adverse events is a challenging aspect of care for girls and women with TS.