• Clinical science

Chromosomal aberrations

Summary

Structural and numerical chromosomal aberrations may affect either the autosomes or gonosomes and are a common cause of spontaneous abortions. Autosomal aberrations that are frequently observed are trisomy 13 (Patau syndrome), trisomy 18 (Edwards syndrome), and the most common and widely recognized chromosomal aberration, trisomy 21 (Down syndrome). These conditions have an extra copy of the chromosome to which their name refer. The risk of autosomal aberrations increases with maternal age. Characteristic features include facial and skeletal malformations, which are usually recognizable at birth. The conditions are further associated with congenital heart defects and malformations of other internal organs. Turner syndrome and Klinefelter syndrome are gonosomal aberrations in which individuals have a missing X chromosome or an additional X chromosome, respectively. These conditions are primarily characterized by impaired development of secondary sexual characteristics and infertility secondary to gonadal dysgenesis. The diagnosis for all chromosomal aberrations is confirmed via karyotyping.

General information

Definitions

Epidemiology

  • Chromosomal aberrations are the most common cause of spontaneous abortions (accounting for 60% of cases).
    • Approx. 50% of anomalies are trisomies.
    • Approx. 20% of anomalies are triploidies.

Overview of viable numerical chromosomal aberrations

References:[1]

Trisomy 13 (Patau syndrome)

  • Karyotype: : 47 XX+13; : 47 XY+13
  • Frequency: ∼ 1:10,000 children
  • Clinical features
    • Microcephaly, holoprosencephaly
    • Cleft lip and palate; , Cutis aplasia (“punched-out” scalp lesions), low-set malformed ears, bulbous nose, small chin
    • Microphthalmia, possibly coloboma , ocular hypotelorism
    • Polydactyly, primarily hexadactyly, flexed fingers
    • Congenital heart defects (particularly ventricular septal defect, patent ductus arteriosis)
    • Rocker-bottom feet
    • Visceral and genital anomalies, especially of the kidneys and ureter
    • Capillary hemangioma
  • Diagnostics: See prenatal diagnostics.
    • Usually detected during first trimester screening with combined ultrasound and maternal serum testing (↓↓ PAPP-A, nuchal translucency)
  • Prognosis: Only 5% of infants survive past 6 months of age.

References:[2][3][4][5][6][7][8]

Trisomy 18 (Edwards syndrome)

  • Karyotype: : 47 XX+18; : 47 XY+18
  • Frequency: ∼ 1:6,000 children
  • Gender: >
  • Clinical features
  • Diagnosis See prenatal diagnostics.
    • Commonly detected in the second trimester screening: quadruple test shows ↓ free estriol, AFP, Inhibin A, and ↓ β-HCG
  • Prognosis: Only 5–10% of patients survive past 12 months of age.

References:[3][6][8]

Down syndrome (trisomy 21)