Turner Syndrome (45,X)

 

Epidemiology and Etiology:

    • 1:2000 – 5000 livebirths
    • One of the most common chromosome abnormalities in spontaneous abortions
      • Estimated 1-2% of conceptuses
      • 99% of 45,X fetuses spontaneously abort by 28 weeks
    • 45,X (50% of Turner)
      • X is maternal in origin 75% of the time
      • No parental age effect
    • Turner syndrome variants:
      • Structurally abnormal sex chromosome (47%)
        • Structurally abnormal X (41%)
          1. i(X)(q10) (18%)
            1. most commonly in mosaicism with 45,X
          2. r(X) (15%)
            1. most commonly in mosaicism with 45,X
        • Structurally abnormal Y (6%)
      • 45,X mosaicism (with 46,XX or 46,XY) (15-20%)
        • It has been proposed that ALL surviving 45,X patients have some form of cryptic mosaicism
      • 45,X/47,XXX mosaicism (2%)
        • Milder phenotype in general

 

Common sites:

    •  

 

Gross features:

    • Hydrops fetalis maybe
    • Decreased birth weight
      • Short stature
    • Facies
      • Posteriorly rotated ears
      • Down-slanting eyes maybe
      • Low posterior hairline maybe
    • Neck webbing
    • Broad chest
    • Edema of hands and feet
    • Short 4th metacarpals
    • Cubitus valgus
    • Congenital heart defects (common)
      • Coarctation of the aorta especially
    • Structural renal anomalies (common)
    • Lack of secondary sexual characteristics (without hormonal supplementation)
    • Streak ovaries
    • External genitalia features may range from normal male to ambiguous to female in 45,X/46,XY mosaicism
      • Phenotype does not correlate with the number of Y-containing cells

 

Histologic features:

    •  

 

Immunophenotype:

Marker:

Sensitivity:

Specificity:

 

 

 

 

Molecular features:

    • SHOX gene on distal part of pseudoautosomal region of Xp
      • Escapes X inactivation
      • Haploinsufficiency causes short stature and Turner skeletal features

 

Other features:

    • Intelligence average to above average
    • Neurocognitive defects (not generalized mental retardation)
      • Visual-spatial and visual-perceptual defects
      • Impaired motor function
      • Impaired nonverbal memory
      • Impaired executive function
      • Impaired attention
      • Nonverbal learning disability
        • Defects in arithmetic, mathematics, and science
        • Impaired adaptation to novel situations
        • Impaired social competence
        • Anxiety and depression
    • Hydrops fetalis maybe
    • Ultrasound:
      • Septate cystic hygroma
      • Cardiac defects
      • Renal anomalies
    • Primary amenorrhea
    • The presence of Y mosaicism imparts a risk of gonadoblastoma

 

References:

·         Evans MI, ed.  Prenatal Diagnosis (2006)

·         Ross J, Roeltgen D, Zinn A.  Cognition and the sex chromosomes: studies in Turner syndrome.  Horm Res.  2006;65(1):47-56.

·         Gersen SL, Keagle MB, eds.  The Principles of Clinical Cytogenetics (2005).