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. Xp material. Ex. 46,iX(Xq) Ex. 46,iX(Xq) 4. Loss of the SHOX gene. Variety of Turner syndrome. Variety of Turner syndrome.
45, X0 – Turner syndromes 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
Phenotype 95% of adult with 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). 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.
Lymphedema May be present at any age. May be present at any age. It is the cause of the and low It is the cause of the webbed neck and low. posterior hairline. In infants, the combination of dysplastic or In infants, the combination of dysplastic or and gives a hypoplastic nails and lymphedema gives a characteristic to the fingers and toes. characteristic sausage-like appearance to the fingers and toes.
Lymphedema 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. 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. 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 5 months until the age of 8 years. Every 6-12 months thereafter. Every 6-12 months thereafter.
At birth At 1 year-age. Before entering school. At adulthood. Hearing assessment
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. 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: Gastrointestinal bleeding: Hip dislocation: Hip dislocation: Scoliosis in 10% of adolescent girls with Turner syndrome. Scoliosis in 10% of adolescent girls with Turner syndrome. Thyroid: 10-30% develop hypothyroidism. Thyroid: 10-30% develop hypothyroidism.
Should be considered in Individuals with : Primary or secondary amenorrhea. Primary or secondary amenorrhea. Adult women with unexplained infertility Adult women with unexplained infertility Unexplained short stature. 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.
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
Cecilia takes her daily growth hormone injection Growth hormone therapy is standard to prevent short stature as an adult. Medical Care In 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 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 years. age years.
Prophylaxis is required prior to and dental or surgical procedure in women with cardiac valve disease, to prevent subacute bacterial endocarditis. Keloid formation Turner syndrome individuals exhibits high risk of keloid formation. Subacute bacterial endocarditis
Before After surgery
Ovarian failure are risk factors for osteoporosis thus adequate daily intake of calcium ( g) and vitamin D (at least 400 IU) should consider. 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. Patients with short stature require fewer calories than those of normal height.
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 offspring. offspring. Consultation with a geneticist 1. Suspected mosaicism for all, or part 1. Suspected mosaicism for all, or part 2. Virilization with part of Y chromosome. 2. Virilization with part of Y chromosome. Genetics counseling
Overall prognosis is good. 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 retardation. retardation. Life expectancy is slightly shorter. Almost all individuals will be infertile, but Almost all individuals will be infertile, but pregnancy with donor embryos is possible. pregnancy with donor embryos is possible.
Yearly follow-up TSH tests will help avoid unrecognized, which can interfere with growth. 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. 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 Barr Bodies are inactivated X chromosomes in Females 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 syndromes and 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 Inactivation
Random inactivation early in dev. A precursor cell to all coat color cells Lyon-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 Inactivation of one X chromosome Regions where sweat glands are absent. Anhidrotic ectodermal dysplasia in a heterozygous woman