45 X Karyotype syndrome. 45 X Karyotype syndrome. Bonnevie-Ullrich syndrome. Bonnevie-Ullrich syndrome. Gonadal dysgenesis. Gonadal dysgenesis. Monosomy X. Monosomy X.
1 in 2,000 live-born female infants. 1 in 2,000 live-born female infants. 15% of spontaneous abortions have 15% of spontaneous abortions have
a 45,X0 Karyotype.a 45,X0 Karyotype.
In Sudan ?In Sudan ?
Race
No racial or ethnic predilections.No racial or ethnic predilections.
Genetic mechanisms Genetic mechanisms 1. Absence of one copy of X chromosome. 1. Absence of one copy of X chromosome.
Paternal loss in 62%Paternal loss in 62% Maternal in 48%Maternal in 48%
2. Patient with Mosaic karyotype.2. Patient with Mosaic karyotype.
Ex. 46,XXEx. 46,XX/45,X/45,X
3. Structural rearrangement result in loss of 3. Structural rearrangement result in loss of
Xp material.Xp material. Ex. 46,iX(Xq)Ex. 46,iX(Xq)
4. 4. Loss of the Loss of the SHOXSHOX gene. gene.
Variety of Turner syndrome.Variety of Turner syndrome.
45 ,X0 – Turner syndromes
http://www.gfmer.ch/Genetic_diseases/Turner_syndrome/Turner.htm
Total fetal hydrops
normal intelligence; may have 3D spatial problems
or math problems.
99% of cases – aborted
1 in 2,500 or 1 in 2,000
liveborn females.
PhenotypePhenotype
95% of adult with 95% of adult with
Turner syndrome Turner syndrome
exhibit exhibit short stature
and and infertility..
94% of patients are infertile 94% of patients are infertile Pregnancy has been achieved by:Pregnancy has been achieved by:
1. Fresh embryo.1. Fresh embryo.
2. Frozen embryo transfer.2. Frozen embryo transfer.
Delivery by caesarean section is Delivery by caesarean section is
related to small pelvic outlet size.related to small pelvic outlet size.
46,X,del(X)(p11)[11].
Age 7 month
Sex Male
DiagnosisIntersex
Examination Big phallus, Labia major. Small L. minora. Blind vagina. Male urethra.Ultrasound NO uterus. Testes could be identified.
LymphedemaLymphedema
May be present at any age. May be present at any age. It is the cause of the It is the cause of the webbed neck and low and low
posterior hairline. . In infants, the combination of In infants, the combination of dysplasticdysplastic or or
hypoplastic nails and and lymphedema gives a gives a
characteristic characteristic sausage-like appearance to to the fingers and toes.the fingers and toes.
Hyperconvex nails in Turner syndrome Hyperconvex nails in Turner syndrome note U-shaped cross sectionnote U-shaped cross section
Mortality and morbidity Mortality Is high due to:Is high due to: 1. Coarctation of the aorta. 1. Coarctation of the aorta. 2. Cardiovascular disease.2. Cardiovascular disease. 3. Obesity, associated diabetes and hypertension. 3. Obesity, associated diabetes and hypertension. 4. Osteoporosis.4. Osteoporosis.
Life expectancy is reduced by 10 years.Life expectancy is reduced by 10 years.
Morbidity
Individuals with mitral or aortic valve disease require Individuals with mitral or aortic valve disease require prophylaxis for sub acute bacterial endocarditis (SBE).prophylaxis for sub acute bacterial endocarditis (SBE).
35% of patients have renal anomalies.35% of patients have renal anomalies. Ultrasound evaluation at the diagnosis. Ultrasound evaluation at the diagnosis. Yearly urine culture.Yearly urine culture. BUN, and creatinine.BUN, and creatinine.
Girls with horseshoe kidneys:Girls with horseshoe kidneys: Have an increased risk of Wilms tumor. Have an increased risk of Wilms tumor. Should have renal ultrasound examinations: Should have renal ultrasound examinations: Every 5 months until the age of 8 years. Every 5 months until the age of 8 years. Every 6-12 months thereafter.Every 6-12 months thereafter.
At birth At birth
At 1 year-age. At 1 year-age.
Before entering school.Before entering school.
At adulthood.At adulthood.
Hearing assessment
A cardiologist should evaluate patients at diagnosis.A cardiologist should evaluate patients at diagnosis.
1. Risks of aortic root dilatation. 1. Risks of aortic root dilatation.
2. Risks of Aortic dissection. 2. Risks of Aortic dissection.
Complete cardiovascular evaluationComplete cardiovascular evaluation
For all patients prior to attemptingFor all patients prior to attempting
assisted reproduction or conception.assisted reproduction or conception.
Supplement with:
1. Growth hormone. 1. Growth hormone. 2. Estrogens.2. Estrogens.
3. progestins.3. progestins.
Attention should be paid to:
1. 1. Growth and development, Growth and development, 2. Thyroid status2. Thyroid status3. Osteoporosis. 3. Osteoporosis.
Patients on growth hormone should be seen every 3-4 months.Patients on growth hormone should be seen every 3-4 months.
Other Other Gastrointestinal bleeding: Gastrointestinal bleeding: Hip dislocation: Hip dislocation: Scoliosis in 10% of adolescent girls with Scoliosis in 10% of adolescent girls with
Turner syndrome.Turner syndrome.Thyroid: 10-30% develop hypothyroidism.Thyroid: 10-30% develop hypothyroidism.
Should be considered in Individuals with :Should be considered in Individuals with :Primary or secondary amenorrhea. Primary or secondary amenorrhea. Adult women with unexplained infertilityAdult women with unexplained infertilityUnexplained short stature.Unexplained short stature. Turner syndrome may be diagnosed prenatally by: 1. Amniocentesis.2. Chorionic villous sampling..
The clinical suspicionThe clinical suspicion Cytogenetic analysisCytogenetic analysis
45,X. 45,X. 45, X/46, XX. 45, X/46, XX. 46,XX,del(X)(P10).46,XX,del(X)(P10).
FFIISSH H analysis.analysis. Cytogenetic analysis of fibroblas Cytogenetic analysis of fibroblas in case of normal karyotype 46,XX.in case of normal karyotype 46,XX.
45 ,X0 – Turner syndromesShort 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
Cecilia takes her daily growth hormone injection
Growth hormone Growth hormone therapy is standard therapy is standard to prevent short statureto prevent short statureas an adult. as an adult.
Medical Care
In childhoodIn childhood
"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 replacementEstrogen replacement
Therapy is required, but starting too Therapy is required, but starting too
early can compromise adult height.early can compromise adult height. Estrogen usually is started from Estrogen usually is started from
age 12-15 years.age 12-15 years.
Prophylaxis is required prior to anddental or surgical procedure in womenwith cardiac valve disease, to preventsubacute bacterial endocarditis.
Keloid formationTurner syndrome individuals exhibits high risk of keloid formation.
Subacute bacterial endocarditis
Ovarian failure are risk factors for Ovarian failure are risk factors for osteoporosis thus adequate daily osteoporosis thus adequate daily intake of calcium (1.0-1.5 g) and intake of calcium (1.0-1.5 g) and vitamin D (at least 400 IU) should vitamin D (at least 400 IU) should consider.consider.
Patients with short stature require Patients with short stature require fewer calories than those of normal fewer calories than those of normal height.height.
Turner syndrome is not an inherited Turner syndrome is not an inherited
disorder, and the recurrence risk is low. disorder, and the recurrence risk is low. Due to infertility, it is rarely passed to Due to infertility, it is rarely passed to
offspring. offspring. Consultation with a geneticist Consultation with a geneticist
1. Suspected mosaicism for all, or part1. Suspected mosaicism for all, or part
2. Virilization with part of Y chromosome. 2. Virilization with part of Y chromosome.
Genetics Genetics counselingcounseling
Overall prognosis is good.Overall prognosis is good. Even with growth hormone therapy, most Even with growth hormone therapy, most
individuals will be shorter than average.individuals will be shorter than average. Turner syndrome is not a cause of mental Turner syndrome is not a cause of mental
retardation.retardation.
Life expectancyLife expectancy is slightly shorter. is slightly shorter. Almost all individuals will be Almost all individuals will be infertileinfertile, but , but
pregnancy with donor embryos is possible.pregnancy with donor embryos is possible.
Yearly follow-up Yearly follow-up TSH testsTSH tests will help will help avoid unrecognized avoid unrecognized hypothyroidism, , which can interfere with growth.which can interfere with growth.
OsteoporosisOsteoporosis and and aortic arch aortic arch dissectiondissection are known complications in are known complications in adulthood.adulthood.
Dosage Dosage CompensationCompensationShouldn’t XX females Shouldn’t XX females
produce twice the amount of produce twice the amount of X-linked gene products X-linked gene products (proteins) as XY males?(proteins) as XY males?
No, because XX females No, because XX females “compensate” by “compensate” by inactivating one of their X inactivating one of their X chromosomes to make a chromosomes to make a single “dosage” of X-linked single “dosage” of X-linked genes.genes.
Barr Bodies are inactivated Barr Bodies are inactivated X chromosomes in FemalesX chromosomes in Females
0 1
2 3
Normal male,Turner female
Normal female,Klinefelter male
# Barr bodies=N-1 rule
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?
Inconsistencies between Inconsistencies between syndromes syndromes
and X inactivationand X inactivation
Perhaps not complete inactivation or inactivation does not happen immediately, Then some overexpression of X-linked genes
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
The Lyon Hypothesis of X The Lyon Hypothesis of X InactivationInactivation
Random inactivation early in dev.
A precursor cell to all coat color cells
Lyon-Hypothesis: X-inactivationLyon-Hypothesis: X-inactivation
**Also in calico cats
X chromosome inactivation
Inactivation is random during development
Color pattern seen in female calico cats due to random 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
Mosaicism Reveals the Random Mosaicism Reveals the Random Inactivation of one X chromosomeInactivation of one X chromosome
Regions whereRegions wheresweat glandssweat glandsare absent.are absent.
Anhidrotic ectodermal Anhidrotic ectodermal dysplasia in a heterozygous dysplasia in a heterozygous womanwoman