45 X Karyotype syndrome. 45 X Karyotype syndrome. Bonnevie-Ullrich syndrome. Bonnevie-Ullrich syndrome. Gonadal dysgenesis. Gonadal dysgenesis. Monosomy X. Monosomy X.

Henry Turner, 1938

Ford et al., 1959

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.

Web of skin

Aorta

Breast development

Under- developed ovaries

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.

Ovarian failure primary amenorrohoae. Undeveloped breast.

45,X[6]/46XX [80]

Ambiguous genitaliaAmbiguous genitalia

Patients may present withPatients may present with

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.

.

Low hairline. Shield-shaped chest. Narrow hip development.

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.

LymphedemaLymphedemaThe 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 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.

FISHFISH

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

Before

After surgery

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

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