Chromosomal causes of infertility/disorders of sexual differentiation Flashcards
Features of Turner syndrome? (8)
Failure to enter puberty/develop 2ndry sexual characteristics Infertility Short stature Coarctation of the aorta Structural renal abnormalities Webbed neck Peripheral oedema Lower IQ than siblings
How does mosaic Turners differ?
May show fewer symptoms
How can Turner’s females have children?
IVF with donor eggs
Turners recurrence risk?
If 45, X then recurrence risk is low; but if structurally abnnormal (i.e. 46,XX but one is normal and other is abnormal) then need to request maternal blood sample to karyotype and estimate recurrence risk
Where do the majority of Turners syndrome come from?
Non-disjunction in the father
Testing performed for Turner’s syndrome?
Karyotype analysis on blood sample in lithium heparin (for infertility)
Can also test prenatally
Turnaround time for Turner’s sample?
Postnatal karyotype analysis- 28 days (different if prenatal)
In partial X-chromosome deletions, what does the effect on fertility depend on?
The position of the breakpoints- the more proximal, the more severe the effect
When do Xq deletions result in ovarian failure?
If they involve the critical region for ovarian failure (Xq13-q26)
X deletion phenotypes:
a) Xp22.22
b) Xp11
c) Xp21
a) SHOX gene, leads to short stature if disrupted
b) primary amenorrhoea
c) secondary amenorrhoea
Symptoms of Klinefelter syndrome?
Small testes- involute after puberty
Gynaecomastia
Infertility
Low testosterone levels
How can patients with Klinefelters have children?
ICSI may be possible if there are some sperm
Incidence of XXY?
1 in 500-1000 newborn males
How is Klinefelter’s usually diagnosed?
Fertility problems, incidental finding, occasionally mild development delay in childhood
Recurrence risk for XXY?
Very low- almost all cases due to non-disjunction
Testing performed for XXY and turnaround time?
Karyotype, blood sample in lithium heparin, 28 days
Y chromosome microddeletion phenotypes?
AZFa = no sperm, no treatment
AZFb = no sperm, no treatment
AZFc = some sperm may be available, consider TESE and ICSI
AZFbc no sperm, no treatment
AZFabc = this is most likely due to an abnormal karyotype
How would a male with an isodicentric Y chromosome present?
Phenotypically male (because SRY present) but lack of spermatogenesis due to lack of AZF region in long arm
Specimen recieved/test performed for Y chromosome microdeletions?
Blood sample in EDTA
ARMS
Why do the majority of individuals with balanced X-autosome translocations have no phenotype?
Get selection for inactivation for the normal X chromosome- may get symptoms if X-inactivation is skewed
Phenotype of men with X-autosome translocations?
Infertile
What happens if critical region on the X chromosome for POF is involved in an X-autosome translocation?
May be a risk of gonadal dysgenesis and primary amenorrhoea
In X-autosome translocation, if the breakpoint disrupts a disease gene then what may happen?
The woman may manifest an X-linked disorder
How do individuals with reciprocal autosomal translocations present?
Infertility/miscarriage/incidental/family contact tracing
