Structural Chromosomal Abnormalities - Lecture 4

Question 1

Clinical Indicators of Chromosomal Abnormalities

Answer 1

• ID
• POF
• DD
• Dysmorphic features
• Neonatal death
• Neoplasia
• Family history
• Reproductive loss
• Congenital heart defects

Question 2

Trisomies

Answer 2

• 13, 18, 21 most common livebirths
• 16 most common overall but no livebirths
• 21 most common livebirth
• 60% of trisomies occur in maternal meiosis
• 90% of trisomies occur in meiosis I
• Trisomy 18 is the exception - Occurs in Meiosis II

Question 3

Advanced Maternal Age

Answer 3

-Approximately 20-25% of oocytes are chromosomally abnormal –> believed to be due to declining structural integrity of meiotic spindle apparatus as age increases

Question 4

Triploidy

Answer 4

69 Chromosomes

• Accounts for 17% of all SABs and 1-3% of all clinically recognized pregnancies
• 90% caused by dispermy (diandry)
• 3-4 syndactyly
• Congenital heart defects
• Holoprosencephaly
• Can survive to livebirth, usually by mosaicism with diploid cell line (usually digyny with diploid line from inclusion of 2nd polar body)

Question 5

Tetraploidy

Answer 5

• failure of cytoplasmic cleavage at first zygotic division
• rarely proceeds beyond 4-5 weeks
• never survives to term without mosaicism

Question 6

Why do trisomies fare better than monosomies

Answer 6

• Regulatory mechanisms may prevent overexpression of extra gene but will not upreglate a missing gene
• Unmasking of deleterious recessive alleles

Question 7

Trisomy 21 Stats

Answer 7

Down Syndrome

• Most frequent trisomy (1/800 - 1/1000 livebirths)
• 75% occurs during meiosis I
• 90-95% are of maternal origin
• 3-4% are translocation trisomy (45 chromosomes)
• 21-21 translocations lead to 100% offspring with trisomy 21
• 2% are mosaic likely due to loss of extra chromosome during development

Question 8

Trisomy 21 Features

Answer 8

• hypotonia most common feature
• upslanted palpebral fissure
• loose neck skin
• 50% have congenital heart defects
• 60% have hearing loss

Question 9

Trisomy 18

Answer 9

Edward syndrome

• Mostly due to nondisjunction in meiosis II
• Some relation to AMA
• 1% recurrence risk
• Only 2-5% survive first year
• Clenched hands, rocker bottom feet

Question 10

Trisomy 13

Answer 10

Patau syndrome

• Wide phenotypic variation
• High mortality
• 80% die within first month
• Mosaicism possible
• Holoprosencephaly, cleft lip and palata, polydactyly, polycystic kidneys

Question 11

Trisomy 8 Mosaicism

Answer 11

• Most common after the main 3
• life expectancy normal in mosaics (non-mosaics do not survive)
• long, narrow face; marfanoid habitus; deep creases in palms and soles

Question 12

Trisomy 16 Mosaicism

Answer 12

• Leads to excess females
• Varying phenotype
• Congenital heart defects, hypospadias, hernia, clubfoot

Question 13

Maternal UPD 16

Answer 13

Most common UPD

• May be phenotypically normal
• Rarely live more than 4 years
• Growth retardation
• Rarely malformations