4Frequency In Sudan ? 1 in 2,000 live-born female infants. 15% of spontaneous abortions have a 45,X0 Karyotype.In Sudan ?RaceNo racial or ethnic predilections.
5Genetic 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,X3. Structural rearrangement result in loss ofXp material. Ex. 46,iX(Xq)4. Loss of the SHOX gene. Variety of Turner syndrome.
16Ambigious genitalia 46,X,del(X)(p11). Age Sex Diagnosis 7 monthSexMaleDiagnosisIntersexExaminationBig phallus,Labia major.Small L. minora.Blind vagina.Male urethra.UltrasoundNO uterus.Testes could be identified.46,X,del(X)(p11).
17 Low hairline. Shield-shaped chest. Narrow hip development. Patients may present with Low hairline. Shield-shaped chest. Narrow hip development..
18Lymphedema May be present at any age. It is the cause of the webbed neck and lowposterior hairline.In infants, the combination of dysplastic orhypoplastic nails and lymphedema gives acharacteristic sausage-like appearance to the fingers and toes.
19Patients may present with LymphedemaThe toes have the characteristicsausage-like appearance
20Generalized lymphedema Generalized lymphedema. Loose skin folds around the neck will form a webbed neck later in life
21Hyperconvex nails in Turner syndrome note U-shaped cross section
22Mortality 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.MorbidityIndividuals with mitral or aortic valve disease requireprophylaxis for sub acute bacterial endocarditis (SBE).
23Nephrology 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.
24Audiology Hearing assessment At birth At 1 year-age. Before entering school. At adulthood.
25Cardiology Complete cardiovascular evaluation A cardiologist should evaluate patients at diagnosis.1. Risks of aortic root dilatation.2. Risks of Aortic dissection.Complete cardiovascular evaluationFor all patients prior to attemptingassisted reproduction or conception.
26Endocrinology Supplement with: 1. Growth hormone. 2. Estrogens. 3. progestins.Attention should be paid to:1. Growth and development,2. Thyroid status3. Osteoporosis.Patients on growth hormone should be seen every 3-4 months.
27Other Gastrointestinal bleeding: Hip dislocation: Scoliosis in 10% of adolescent girls with Turner syndrome.Thyroid: 10-30% develop hypothyroidism.
28Diagnosis Should be considered in Individuals with : Primary or secondary amenorrhea.Adult women with unexplained infertilityUnexplained short stature.Turner syndrome may be diagnosed prenatally by:1. Amniocentesis.2. Chorionic villous sampling.
29Diagnosis The clinical suspicion Cytogenetic analysis FISH analysis. 45,X.45, X/46, XX.46,XX,del(X)(P10).FISH analysis.Cytogenetic analysis of fibroblasin case of normal karyotype 46,XX.
3345, 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 pressuretreated by growth hormoneestrogen-progesterone treatmentto maintain secondary sexual developmentCorrected surgically
34Medical Care In childhood Growth hormone therapy is standard to prevent short statureas 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."
36Estrogen replacement early can compromise adult height. Therapy is required, but starting tooearly can compromise adult height.Estrogen usually is started fromage years.
37Subacute bacterial endocarditis Surgical CareKeloid formationTurner syndrome individuals exhibitshigh risk of keloid formation.Subacute bacterial endocarditisProphylaxis is required prior to anddental or surgical procedure in womenwith cardiac valve disease, to preventsubacute bacterial endocarditis.
39DietOvarian 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.
40Genetics counseling Turner syndrome is not an inherited disorder, and the recurrence risk is low.Due to infertility, it is rarely passed tooffspring.Consultation with a geneticist1. Suspected mosaicism for all, or part2. Virilization with part of Y chromosome.
41Life expectancy is slightly shorter. PrognosisOverall prognosis is good.Even with growth hormone therapy, mostindividuals will be shorter than average.Turner syndrome is not a cause of mentalretardation.Life expectancy is slightly shorter.Almost all individuals will be infertile, butpregnancy with donor embryos is possible.
42Medical 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.
44Dosage CompensationShouldn’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.
45Barr Bodies are inactivated X chromosomes in Females Normal female,Klinefelter maleNormal male,Turner female123# Barr bodies=N-1 rule
46Inconsistencies between syndromes and X inactivationIf normal XX female has one X inactivated,why is a X Turner female not normal?Similarly, if XXY male has one Xinactivated, why does he have Klinefeltersyndrome?Perhaps not complete inactivation orinactivation does not happen immediately,Then some overexpression of X-linked genes
47The 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 embryogenesisProgeny of cells all have same inactivated X chromosome as original, creating mosaic individual
48Lyon-Hypothesis: X-inactivation A precursor cell to all coat color cellsRandom inactivation early in dev.**Also in calico cats
49X chromosome inactivation X chromosome has many more genes than the Y chromosomeFemales have 2 XsOne X must be inactivated to preserve gene dosageBarr bodies in female cellsInactive Xs condense to form Barr bodies during developmentInactivation is random during developmentColor pattern seen in female calico cats due to random X chromosome inactivation
50Mosaicism Reveals the Random Inactivation of one X chromosome Anhidrotic ectodermaldysplasia in a heterozygous womanRegions wheresweat glandsare absent.