Turner syndrome

Turner syndrome can present prenatally, neonatally, in childhood, during teenage years and beyond, with a range of clinical features, including a raised nuchal translucency, cardiac/renal anomalies, short stature, webbed neck and absent menarche. It is typically a sporadic condition caused by monosomy X, though mosaic individuals are recognised and often have milder features.

• Prenatal:
  • a nuchal translucency that is raised, often significantly so, which may be the result of a cystic hygroma;
  • fetal oedema (hydrops); and
  • 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; and
  • 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 a normal IQ, however a mild cognitive-behavioural phenotype is recognised, including difficulties in visual-spatial function, executive function and emotional processing; and
  • increased risk of certain autoimmune conditions such as diabetes, thyroid disease and coeliac disease.
• Teenage years:
  • all features listed under childhood also apply to teenage years; and
  • the usual puberty associated growth spurt does not occur in Turner syndrome, and/or there are no signs of puberty at all (or menarche is absent), which is usually associated with infertility (streak ovaries).

Turner syndrome occurs when there is an anomaly of one X chromosome. There are a number of ways in which this can happen.

• Monosomy X: By far the most common anomaly to cause Turner syndrome. In monosomy X there is a complete absence of one of the two X chromosomes. This usually occurs due to maternal or paternal nondisjunction.
• Mosaic Turner syndrome may occur where an individual has a combination of cell lines (for example, 45,X/46,XX or 45,X/46,XY).

Females with partial deletion (with or without rearrangement) or mosaic forms may have streak ovaries without the full phenotypic features.

Although Turner syndrome is a condition that primarily affects girls, boys can have a mosaic 45,X/46,XY karyotype with some of the features of Turner syndrome (though this is rare). These individuals are also at risk of gonadoblastoma.

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

Where Turner syndrome is suspected on clinical findings, chromosomal analysis can confirm the diagnosis. Common aneuploidy (QF-PCR) testing will look for the common trisomies (trisomy 21, 18 and 13) as well as sex chromosome anomalies which includes Turner syndrome (45, X).

Where initial testing is normal and the clinical picture is strongly suggestive of Turner Syndrome, a karyotype can be completed with an extended number of cells reviewed in order to identify mosaicism.

Postnatal diagnostic testing is usually completed on blood samples. Prenatal diagnostic testing may be completed on samples obtained via chorionic villus sampling (CVS) or amniocentesis.

For information about testing, see Presentation: Clinical suspicion of Turner syndrome. Prenatally and where nuchal translucency that is raised, consider Presentation: Fetus with raised nuchal translucency.

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

Females with Turner syndrome 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 Turner syndrome have had successful pregnancies through egg donation.

Management of children with Turner syndrome should be delivered via a multidisciplinary team, typically including paediatric, endocrinology, cardiology and genetic teams. You can find management guidelines in the references list below.

For clinicians

• Genomics England: NHS Genomic Medicine Service (GMS) Signed Off Panels Resource
• NHS England: National Genomic Test Directory
• NHS Health A to Z: Turner syndrome
• U.S. National Library of Medicine: ClinicalTrials.gov database

References:

• Gravholt CH, Andersen NH, Christin-Maitre S and others. ‘Clinical practice guidelines for the care of girls and women with Turner syndrome: Proceedings from the 2023 Aarhus International Turner Syndrome Meeting‘. European Journal of Endocrinology 2024: volume 190, issue 6, pages G53–G151. DOI: 10.1093/ejendo/lvae050
• Gravholt CH, Viuff MH, Brun S and others. ‘Turner syndrome: Mechanisms and management’. Nature Reviews Endocrinology 2019: volume 15, pages 601–614. DOI: 10.1038/s41574-019-0224-4

For patients

• National Organization for Rare Disorders: Turner syndrome
• NHS Health A to Z: Turner syndrome
• Turner Syndrome Support Society