1. Turner Syndrome

2. Synonyms and related keywords
45 X Karyotype syndrome.
Bonnevie-Ullrich syndrome.
Gonadal dysgenesis.
Monosomy X.

3. History
 Henry Turner, 1938
 Ford et al., 1959

4. Frequency In Sudan ? 1 in 2,000 live-born female infants.
15% of spontaneous abortions have a 45,X0 Karyotype.
In Sudan ?
Race
No racial or ethnic predilections.

5. Genetic mechanisms 1. Absence of one copy of X chromosome.
 Paternal loss in 62%
 Maternal in 48%
2. Patient with Mosaic karyotype.
 Ex. 46,XX/45,X
3. Structural rearrangement result in loss of
Xp material.
 Ex. 46,iX(Xq)
4. Loss of the SHOX gene.
 Variety of Turner syndrome.

9. may have 3D spatial problems
45, X0 – Turner syndromes
99% of cases
– aborted
Total fetal
hydrops
1 in 2,500 or
1 in 2,000
liveborn females.
normal intelligence;
may have 3D spatial problems
or math problems.

10. Web of skin
Aorta
Breast development
Under- developed ovaries

11. Phenotype 95% of adult with Turner syndrome exhibit short stature
and infertility.

12. Short stature

13. Infertility  94% of patients are infertile
 Pregnancy has been achieved by:
1. Fresh embryo.
2. Frozen embryo transfer.
 Delivery by caesarean section is
related to small pelvic outlet size.

14. Ovarian failure  primary amenorrohoae.  Undeveloped breast.
Patients may present with
Ovarian failure  primary amenorrohoae.  Undeveloped breast.
45,X[6]/46XX [80]

15. Patients may present with
Ambiguous genitalia

16. Ambigious genitalia 46,X,del(X)(p11)[11]. Age Sex Diagnosis
7 month
Sex
Male
Diagnosis
Intersex
Examination
Big phallus,
Labia major.
Small L. minora.
Blind vagina.
Male urethra.
Ultrasound
NO uterus.
Testes could be identified.
46,X,del(X)(p11)[11].

17.  Low hairline.  Shield-shaped chest.  Narrow hip development.
Patients may present with
 Low hairline.  Shield-shaped chest.  Narrow hip development. .

18. Lymphedema May be present at any age.
It is the cause of the webbed neck and low
posterior hairline.
In infants, the combination of dysplastic or
hypoplastic nails and lymphedema gives a
characteristic sausage-like appearance to the fingers and toes.

19. Patients may present with
 Lymphedema
The toes have the characteristic
sausage-like appearance

20. Generalized lymphedema
Generalized lymphedema. Loose skin folds around the neck will form a webbed neck later in life

21. Hyperconvex nails in Turner syndrome note U-shaped cross section

22. Mortality and morbidity
Is high due to:
1. Coarctation of the aorta.
2. Cardiovascular disease.
3. Obesity, associated diabetes and hypertension.
4. Osteoporosis.
Life expectancy is reduced by 10 years.
Morbidity
Individuals with mitral or aortic valve disease require
prophylaxis for sub acute bacterial endocarditis (SBE).

23. Nephrology or urology 35% of patients have renal anomalies.
Ultrasound evaluation at the diagnosis.
Yearly urine culture.
BUN, and creatinine.
Girls with horseshoe kidneys:
Have an increased risk of Wilms tumor.
Should have renal ultrasound examinations:
 Every 5 months until the age of 8 years.
 Every 6-12 months thereafter.

24. Audiology Hearing assessment  At birth  At 1 year-age.
 Before entering school.
 At adulthood.

25. Cardiology Complete cardiovascular evaluation
A cardiologist should evaluate patients at diagnosis.
1. Risks of aortic root dilatation.
2. Risks of Aortic dissection.
Complete cardiovascular evaluation
For all patients prior to attempting
assisted reproduction or conception.

26. Endocrinology Supplement with: 1. Growth hormone. 2. Estrogens.
3. progestins.
Attention should be paid to:
1. Growth and development,
2. Thyroid status
3. Osteoporosis.
Patients on growth hormone should be seen every 3-4 months.

27. Other Gastrointestinal bleeding: Hip dislocation:
Scoliosis in 10% of adolescent girls with Turner syndrome.
Thyroid: 10-30% develop hypothyroidism.

28. Diagnosis Should be considered in Individuals with :
Primary or secondary amenorrhea.
Adult women with unexplained infertility
Unexplained short stature.
Turner syndrome may be diagnosed prenatally by:
1. Amniocentesis.
2. Chorionic villous sampling.

29. Diagnosis The clinical suspicion Cytogenetic analysis FISH analysis.
45,X.
45, X/46, XX.
46,XX,del(X)(P10).
FISH analysis.
Cytogenetic analysis of fibroblas
in case of normal karyotype 46,XX.

32. FISH

33. 45, X0 – Turner syndromes
Short Stature (approximately 4 feet 8 inches) –;
loss of action SHOX gene on the X-chromosome.
No ovarian function or early loss of function (in late teens)
Coarctation of the aorta (narrow aorta) 10-15%
Kidney problem (Horseshoe kidney)  high blood pressure
treated by growth hormone
estrogen-progesterone treatment
to maintain secondary sexual development
Corrected surgically

34. Medical Care In childhood Growth hormone therapy is standard
to prevent short stature
as an adult.
Cecilia takes her daily growth hormone injection

35. "My name is Regina and I’m 9 years old
"My name is Regina and I’m 9 years old. I felt that taking my growth hormone injection was a bit difficult in the beginning, but I practiced with an orange and after a while I found out how to do it, and now it’s just a habit like brushing your teeth."

36. Estrogen replacement early can compromise adult height.
Therapy is required, but starting too
early can compromise adult height.
Estrogen usually is started from
age years.

37. Subacute bacterial endocarditis
Surgical Care
Keloid formation
Turner syndrome individuals exhibits
high risk of keloid formation.
Subacute bacterial endocarditis
Prophylaxis is required prior to and
dental or surgical procedure in women
with cardiac valve disease, to prevent
subacute bacterial endocarditis.

38. Surgical Care
Before
After surgery

39. Diet
Ovarian failure are risk factors for osteoporosis thus adequate daily intake of calcium ( g) and vitamin D (at least 400 IU) should consider.
Patients with short stature require fewer calories than those of normal height.

40. Genetics counseling Turner syndrome is not an inherited
disorder, and the recurrence risk is low.
Due to infertility, it is rarely passed to
offspring.
Consultation with a geneticist
1. Suspected mosaicism for all, or part
2. Virilization with part of Y chromosome.

41. Life expectancy is slightly shorter.
Prognosis
Overall prognosis is good.
Even with growth hormone therapy, most
individuals will be shorter than average.
Turner syndrome is not a cause of mental
retardation.
Life expectancy is slightly shorter.
Almost all individuals will be infertile, but
pregnancy with donor embryos is possible.

42. Medical and legal pitfalls
Yearly follow-up TSH tests will help avoid unrecognized hypothyroidism, which can interfere with growth.
Osteoporosis and aortic arch dissection are known complications in adulthood.

44. Dosage Compensation
Shouldn’t XX females produce twice the amount of X-linked gene products (proteins) as XY males?
No, because XX females “compensate” by inactivating one of their X chromosomes to make a single “dosage” of X-linked genes.

45. Barr Bodies are inactivated X chromosomes in Females
Normal female,
Klinefelter male
Normal male,
Turner female 1 2 3
# Barr bodies=
N-1 rule

46. Inconsistencies between syndromes
and X inactivation
If normal XX female has one X inactivated,
why is a X Turner female not normal?
Similarly, if XXY male has one X
inactivated, why does he have Klinefelter
syndrome?
Perhaps not complete inactivation or
inactivation does not happen immediately,
Then some overexpression of X-linked genes

47. The Lyon Hypothesis of X Inactivation
Proposed by Mary Lyon and Liane Russell (1961)
Which X is inactivated? Inactivation of X chromosome occurs randomly in somatic cells during embryogenesis
Progeny of cells all have same inactivated X chromosome as original, creating mosaic individual

48. Lyon-Hypothesis: X-inactivation
A precursor cell to all coat color cells
Random inactivation early in dev.
**Also in calico cats

49. X chromosome inactivation
X chromosome has many more genes than the Y chromosome
Females have 2 Xs
One X must be inactivated to preserve gene dosage
Barr bodies in female cells
Inactive Xs condense to form Barr bodies during development
Inactivation is random during development
Color pattern seen in female calico cats due to random X chromosome inactivation

50. Mosaicism Reveals the Random Inactivation of one X chromosome
Anhidrotic ectodermal
dysplasia in a heterozygous woman
Regions where
sweat glands
are absent.

51. Thank you