Turner syndrome

Prenatal:

• A raised nuchal translucency: often this is significantly raised and may be the result of a cystic hygroma.
• Fetal oedema (hydrops).
• Cardiac and/or renal anomalies, particularly coarctation of the aorta and/or horseshoe kidney.

Neonatal:

• Lymphoedema with puffy hands and feet.
• Webbed neck with extra skin fold crease.
• Cardiac and/or renal anomalies, particularly coarctation of the aorta and/or horseshoe kidney.

Childhood:

• Short stature: height is usually normal for the first three years of life but then growth velocity slows.
• Webbed neck and unusual habitus with widened carrying angle and widely spaced nipples.
• Cardiac and/or renal anomalies, particularly coarctation of the aorta and/or horseshoe kidney.
• Recurrent otitis media.
• Typically normal IQ; however, a mild cognitive-behavioural phenotype is recognised, including difficulties in visual-spatial, executive function and emotional processing.
• Increased risk of certain autoimmune conditions, such as diabetes, thyroid disease and coeliac disease.

Teenage years:

• As above with childhood.
• Of note, the usual puberty associated growth spurt does not occur in Turner syndrome; and/or
• no signs of puberty/absent menarche, usually associated with infertility (streak ovaries).

Turner syndrome (TS) occurs when there is an anomaly in an X chromosome. There are a number of ways this can happen, but monosomy X is by far the most common:

• Monosomy X: where there is complete absence of one of the two X chromosomes. This usually occurs due to maternal or paternal nondisjunction.
• Partial deletion or structural rearrangement: where one of the X chromosomes is partially missing +/- structurally rearranged, rather than entirely absent.
• Mosaic Turner syndrome may occur where an individual has a combination of cell lines (such as 45,X/46,XX or 45,X/46,XY).

Females with partial deletion +/- rearrangement/mosaic forms may have streak ovaries without the full phenotypic features.

Turner syndrome is primarily a condition that affects girls but, rarely, boys can have a mosaic 46,XY/45X karyotype with some of the features of TS. These individuals are also at risk of gonadoblastoma.

Individuals with a ring chromosome X can have a more severe phenotype that includes intellectual disability.

Turner syndrome is usually a result of sporadic nondisjunction, or chromosome breakage during gametogenesis (or post-zygotically in mosaic cases), and recurrence risk for parents with a child affected by TS is therefore low (<1%).

In cases of non-mosaic 45,X, parental karyotypes are not routinely requested. If testing reveals a partial deletion or structural rearrangement, it may be helpful to check that the parental chromosomes are normal, for reassurance and to exclude the possibility of a structural rearrangement or rare heritable partial deletion. Women found to be carriers of an X chromosome structural rearrangement have a high recurrence risk.

Females with TS are usually infertile. Most girls have primary amenorrhoea, and for the few who do enter menarche, premature ovarian failure occurs. Spontaneous pregnancy is therefore very rare, although some women with TS have had successful pregnancies through egg donation.

Management of children with TS is complex and should be delivered via a multi-disciplinary team. For links to management guidelines, please see resources below.

For clinicians

• NHS Health A-Z: Turner syndrome
• NHS England: National Genomic Test Directory and eligibility criteria

References:

• Gravholt CH, Viuff MH, Brun S and others. ‘Turner syndrome: mechanisms and management’. National Reviews Endocrinology 2019: volume 15, pages 601-14. doi: 10.1038/s41574-019-0224-4

For patients

• Information on Turner syndrome: Turner Syndrome Support Society
• National Organisation for Rare Disorders: Turner syndrome
• NHS health A-Z: Turner syndrome