Turner Syndrome – 45,X Explained

WHAT IS IT?

• Also known as 45,X ; monosomy X; Turner’s syndrome; Ullrich-Turner syndrome
• A sex chromosome abnormality that involves the presence of one functional X chromosome and no other X or Y chromosome
  • All cells can be monosomy X (having a single X chromosome) or 
  • There can be a mix of cell lines, where some cells are normal (46,XX) and others have only one X chromosome (mosaic Turner syndrome)
• Common findings on prenatal ultrasound:
  • Increased nuchal translucency (1st trimester), nuchal fold (2nd trimester), or cystic hygroma
  • Cardiac defects
    • Bicuspid aortic valve and coarctation of the aorta
  • Renal defects (i.e. horseshoe kidney)
• Other findings may not be apparent until postnatal life
  • Short stature is usually the most consistent finding, approximately 8 inches less than what would be expected for her family
    • Genetic mechanism resulting in short stature still unknown, however the absence of the SHOX gene, located on short arm of X chromosome, which helps coordinate bone development, is likely an important factor
  • Wide or webbed neck
  • Low-set ears
  • Low hairline at the back of the head
  • Broad chest with widely spaced nipples
  • Lymphedema, especially of the hands and feet
  • Absent, delayed, or partial spontaneous pubertal development (30%)
  • Absent or decreased fertility, depending on what percentage of cells have only one X chromosome, as two X chromosomes are required for ovarian development and function
• Intellectual development:
  • Females who have a 45,X karyotype usually have normal intelligence although there may be some learning disabilities, particularly with mathematical and spatial concepts, some difficulty in social situations
• Treatment and monitoring:
  • Cardiology monitoring
  • Growth hormone and hormone replacement therapy
  • Academic support for potential learning challenges
  • Fertility assessment

CAUSE:

Turner syndrome (45,X) is a condition caused by an abnormal karyotype that is present at the time of conception and results from a sperm or egg that is capable of undergoing fertilization, but has no X chromosome. As this appears to be a random event, Turner syndrome is generally not inherited and risk of recurrence in subsequent pregnancies is minimal.

KEY POINTS:

• ACOG requires all women be offered prenatal screening (biochemical/ cfDNA) or invasive diagnostic testing (amniocentesis/ CVS)
  • Turner (45,X) syndrome is included on some cfDNA screening panels but is associated with a higher false positive rate compared to Down syndrome
  • Confirmatory testing (amniocentesis or CVS) should be offered all women with a positive cfDNA screening report
    • Presently, invasive testing is the only way to diagnose fetal Turner syndrome
    • There is data supporting the use of amniocentesis rather than CVS for confirmation
• Present in 1/1500- 1/2500 live births
• Estimated to account for 3% of all conceptions
• Despite relatively functional outcomes, approximately 99% of cases are miscarried or stillborn
  • Mosaic Turner syndrome has a better chance of survival
• ACMG provides ACT sheets to assist healthcare professionals with ‘next steps’ following a positive NIPS report for 45,X (see ‘Learn More – Primary Sources’ below)

Learn More – Primary Sources:

ACMG: Noninvasive Prenatal Screening via Cell-Free DNA ACT Sheet [45,X: Positive Cell Free DNA Screen]

NHGRI: Turner syndrome

US NLM- Genetics Home Reference

The type of feto-placental aneuploidy detected by cfDNA testing may influence the choice of confirmatory diagnostic procedure

ACOG Practice Bulletin 226: Screening for Fetal Chromosomal Abnormalities

Locate a Genetic Counselor or Genetics services:

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC

Genetic Services Locator-CAGC