Presentation: Clinical suspicion of Turner syndrome

A 14-year-old girl is referred to the paediatric clinic by her GP because she hasn’t yet started her period. She is noted to be shorter than other members of the family.

Turner syndrome may be suspected at different ages following different presentations.

• Prenatally:
  • a raised nuchal translucency (often this is significantly raised and may be the result of a cystic hygroma) – see Presentation: Patient with raised nuchal translucency;
  • fetal oedema (hydrops); and
  • cardiac and/or renal anomalies, particularly coarctation of the aorta and/or horseshoe kidney.
• Neonatally:
  • 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;
  • webbed neck and unusual habitus, with widened carrying angle and widely spaced nipples; and
  • cardiac and/or renal anomalies, particularly coarctation of the aorta and/or horseshoe kidney.
• Teenage years:
  • the features listed under the childhood period apply here, plus:
  • no signs of puberty or absent menarche.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see Genomic testing in the devolved nations.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• Decide which of the panels best suits the needs of your patient or family.
  • R26 Likely common aneuploidy: This is a common aneuploidy (QF-PCR) test that looks for trisomy 21, trisomy 18, trisomy 13 and Turner syndrome.
  • R265 Chromosomal mosaicism – karyotype: This may be considered if the clinical picture is strongly suggestive of Turner Syndrome but R26 is negative. The test involves karyotyping an extended number of cells in order to identify mosaicism.
  • R297 Possible structural chromosomal rearrangement – karyotype or targeted chromosome analysis: If any structural chromosome rearrangements or a ring chromosome are suspected, based on findings from whole genome sequencing (WGS), microarray or other laboratory test.
  • R27 Paediatric disorders: This should be considered if there is developmental delay or intellectual disability in association with congenital malformation or overgrowth, and you would like to investigate chromosomal and single-gene causes. The test involves WGS of a large number of panels simultaneously.
    • R27 is an amalgamation of over 10 panels of genes known to be associated with a broad range of paediatric developmental disorders. It may now be ordered directly by paediatricians, though a discussion with clinical genetics services may be beneficial.
• For tests that do not include WGS, including R26, R265 and R297:
  • you can use your local Genomic Laboratory Hub (GLH) test order and consent (record of discussion) forms; and
  • parental samples may be needed for interpretation of the child’s result. Parental samples can be taken alongside that of the child, and their DNA stored, or can be requested at a later date if needed.
• For tests that are undertaken using WGS, including R27, you will need to:
  • complete an NHS GMS test order form with details of the affected individual (proband) and their parents where available, including details of the phenotype (using human phenotype ontology (HPO) terms) and the appropriate panel name(s) with associated R number (see How to complete a test order form for WGS for support in completing WGS-specific forms);
  • complete an NHS GMS RoD form for each person being tested – for example, if you are undertaking trio testing of an affected child and their parents, you will need three RoD forms (see How to complete a record of discussion form for support); and
  • submit parental samples alongside the child’s sample (this is trio testing) to aid interpretation, especially for the larger WGS panels (where this is not possible, for example because the child is in care or the parents are unavailable for testing, the child may be submitted as a singleton).
• The majority of tests are DNA-based, and an EDTA sample (typically a purple-topped tube) is required. Exceptions include karyotype testing and DNA repair defect testing (for chromosome breakage), which require lithium heparin (typically a green-topped tube).
• Most tests are DNA based, and an EDTA sample (typically a purple-topped tube) is required. Exceptions include karyotype testing (R265 and R297) and DNA repair defect testing (for chromosome breakage), which require lithium heparin (typically a green-topped tube). For more information, see Samples for genomic testing in rare disease.
• If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

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

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

• NHS England: Whole genome sequencing patient information leaflets
• NHS Health A to Z: Turner syndrome
• National Organization for Rare Disorders: Turner syndrome
• Turner Syndrome Support Society