Transcript Turner Syndrome Lect

45 X Karyotype syndrome.
 Bonnevie-Ullrich syndrome.
 Gonadal dysgenesis.
 Monosomy X.

 Henry Turner, 1938
 Ford et al., 1959
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.
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.
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.
http://www.gfmer.ch/Genetic_diseases/Turner_syndrome/Turner.htm
Web of skin
Aorta
Breast development
Under- developed ovaries
Phenotype
95% of adult with
Turner syndrome
exhibit short stature
and 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.
Ovarian failure
 primary amenorrohoae.
 Undeveloped breast.
45,X[6]/46XX [80]
Patients may present with
Ambiguous genitalia
Age
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].
 Low hairline.
 Shield-shaped chest.
 Narrow hip development.
.
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.

 Lymphedema
The toes have the characteristic
sausage-like appearance
Generalized lymphedema. Loose skin folds around
the neck will form a webbed neck later in life
Hyperconvex nails in Turner syndrome
note U-shaped cross section
Mortality and morbidity
Mortality
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).
 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.
Hearing assessment
 At birth
 At 1 year-age.
 Before entering school.
 At adulthood.
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.
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.
Other
Gastrointestinal bleeding:
 Hip dislocation:
 Scoliosis in 10% of adolescent girls with
Turner syndrome.
 Thyroid: 10-30% develop hypothyroidism.

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.
The clinical suspicion
 Cytogenetic 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.

FISH
45, X0 – Turner syndromes
Short Stature (approximately 4 feet 8 inches) –;
loss of action SHOX gene on the X-chromosome.
treated by growth hormone
No ovarian function or early loss of function (in late 
teens)
estrogen-progesterone treatment
to maintain secondary sexual development
Coarctation of the aorta (narrow aorta) 10-15%
Corrected surgically
Kidney problem (Horseshoe kidney)  high blood 
pressure
Medical Care
In childhood
Growth hormone
therapy is standard
to prevent short stature
as an adult.
Cecilia takes her daily growth hormone injection
"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."
Estrogen replacement
Therapy is required, but starting too
early can compromise adult height.
 Estrogen usually is started from
age 12-15 years.

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.
Before
After surgery
Ovarian failure are risk factors for
osteoporosis thus adequate daily
intake of calcium (1.0-1.5 g) and
vitamin D (at least 400 IU) should
consider.
 Patients with short stature require
fewer calories than those of normal
height.

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.

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.
 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.
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.
Barr Bodies are inactivated X
chromosomes in Females
Normal male,
Turner female
0
1
2
3
Normal female,
Klinefelter male
# Barr bodies=
N-1 rule
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
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
Lyon-Hypothesis: X-inactivation
A precursor cell to all coat color cells
Random inactivation early in dev.
**Also in calico cats
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
Inactive Xs condense to form Barr
bodies during development
Inactivation is random
during development
Barr bodies in female cells
Color pattern seen in female
calico cats due to random X
chromosome inactivation
Mosaicism Reveals the Random
Inactivation of one X chromosome
Anhidrotic ectodermal
dysplasia in a heterozygous
woman
Regions where
sweat glands
are absent.