Trisomy and Sex Chromosome Abnormalities (Diagnostics L5)

A large majoriity of all conceptions are chromosomally abnormal but most of these conceptions don't result in prenancy or birth.

Study testing 1st trimester miscarriages showed chromosomal abnormalities of 70%

Majority of trisomy's (except 13, 18, 21) will not result in live birth. Triploidy even rarer. Monosomy usually results in miscarriage with exception of sex chromosomes.

Trisomy 16

Most common trisomy in spontaneous pregnancy loss

• 1.5% of all clinically detected pregnancies 
• 7.5% miscarriages
• Full trisomy 16 - minimal embyronic developmetn
• On CVS often mosaicism in placenta only, risk of IUGR, stillbirth and premature delivery
• On amniocentesis often true fetal mosaicism

• Placental sampling between 11-12 weeks – can see some trisomy in some cells = confined placental mosaicism and survival

• Trisomic rescue can remove the extra chromosome in some cells. Results in small babies because placenta is trisomy and so function affected

Trisomy 21

• Down Syndrome
• Incidence - 1/800 live births dependent on maternal age
  • 20-30 year olds have risk of 0.1-0.2% 
  • 40-45 increases to 3.6% risk

  • As age increases the amount of time the eggs have been held in prophase 1 increases 

• Origin
  • 95% nondisjunction - commonly during anaphase I
  • 2% Robertsonian translocation
  • 2% mosaic
  • 1% chromosomal rearrangements (n.b. 21q22)
• Clinical features
  • Distinctive facial features such as upslanting palpebral fissures, epicanthic folds, flat profle with depressed nasal bridge and short nose
  • Single palmar crease - 5% of general popularion have this
  • Hypotonia (floppy baby)
  • Congenital heart disease (40-50%) - atrioventricular septal defect, CHD reduces life expectency from birth
  • Other malformations (duodenal atresia, stenosis, Hirshprung
  • Hyperthyroidism (20-40%) - late onset
  • Leukaemia (ALL in c.2%)
  • Short stature
  • Developmental delay and learning probelems
  • Dementia (cognitive decline at 30-40years)
• Mean age of death = 49 years

Trisomy 18

• Edward's syndrome
• Incidence 
  • 1/7900 live births
  • 3:1 female:male
• Origin
  • 90% maternal nondisjunction
  • 10% mosaic
  • <1% translocation
• Clinical features
  • Intrauterine growth retardation
  • Strawberry shaped calvarium (jaw area), prominent occiput (back of head)
  • Brain malformation - can stop breathing as brain doesn't remind them to
  • Micrognathia (jaw undersized),…