Presented by Rebecca Singleton
Turner Syndrome Overview; What Is It? <ul><li>Birth defect, only seen in women </li></ul><ul><li>Congenital absence of X-...
Turner Syndrome Overview <ul><li>1 in 2000-2500 live female births </li></ul><ul><li>Not a hereditary disease, except in r...
Turner Syndrome Genotype: 45 X; What Does It Look Like?
Normal Gametogenesis: How Does It Happen? <ul><li>Spermatocytes are formed from sperm cell precursors </li></ul><ul><li>C...
Abnormal Gametogenesis Leading to Turner Syndrome: How Does It Happen? <ul><li>X or Y chromosome gets lost </li></ul><ul>...
Mosaics: How Do They Happen? Normal, fertilized egg Normal Mitosis X chromosome lost from developing embryo Resulting in ...
Turner Syndrome Phenotype: What Is the Distribution? Note: 98% infertile and 95% have ovarian failure                    ...
Turner Syndrome Phenotype: What Is Affected? <ul><li>Affected Body Systems </li></ul><ul><ul><li>Lymphatics </li></ul></u...
Turner Syndrome Phenotype <ul><li>Lymphatic Defects </li></ul><ul><ul><li>Contribute to </li></ul></ul><ul><ul><ul><li>Na...
Nail Deformity <ul><li>Affects 70% of patients </li></ul><ul><li>Caused by peripheral lymphedema </li></ul><ul><li>Small, ...
Webbed Neck <ul><li>Affects 25% of patients </li></ul><ul><li>Jugular lymph sacs fail to drain properly </li></ul><ul><li>...
Cystic Hygroma <ul><li>Most concepti with 45 X spontaneously abort </li></ul><ul><li>15% of spontaneous abortions have a g...
Other Lymphatic Defects <ul><li>Cystic hygroma also causes </li></ul><ul><ul><li>Low hairline </li></ul></ul><ul><ul><li>L...
Cardiovascular Defects <ul><li>May result from defective lymphatics as well </li></ul><ul><li>Present in 1/3 of cases </li...
Renal Defects <ul><li>Usually benign </li></ul><ul><li>Most common horseshoe kidney </li></ul><ul><ul><li>10% </li></ul><...
Eyes, Ears and Skin <ul><li>Eyes </li></ul><ul><ul><li>Strabismus </li></ul></ul><ul><ul><li>Ptosis </li></ul></ul><ul><li...
Orthopedic Disorders <ul><li>Growth problems </li></ul><ul><ul><li>Delayed growth </li></ul></ul><ul><ul><li>Not uniform <...
Orthopedic Disorders <ul><li>Scoliosis in 12% of patients </li></ul><ul><li>Genus Valgus (knock knees) in 60% </li></ul><...
Reproductive Defects <ul><li>Ovarian dysgenesis </li></ul><ul><ul><li>95% </li></ul></ul><ul><ul><li>Delayed or absent se...
Chronic Problems <ul><li>Thyroid problems </li></ul><ul><ul><li>Hashimoto thyroiditis (autoimmune hypothyroidism) </li></u...
Turner Syndrome Phenotype: Example <ul><li>Short stature </li></ul><ul><li>Webbed neck </li></ul><ul><li>Shield-like chest...
Turner Syndrome Phenotype: Example <ul><li>Low hairline </li></ul><ul><li>Broad chest </li></ul><ul><li>Narrow hips </li><...
Turner Syndrome Phenotype: Example <ul><li>Marked edema </li></ul><ul><li>Many times first indication of syndrome </li></u...
Turner Syndrome Phenotype: Example <ul><li>Generalized lymphedema </li></ul><ul><li>Loose skin folds at neck </li></ul><ul...
Reproductive Anatomy of Turner Syndrome <ul><li>Streak ovaries present </li></ul><ul><li>Long, thin bands of ovarian tissu...
Anatomy of Heart
Aortic Dissection <ul><li>Artery lining tears or is damaged </li></ul><ul><li>Blood leaks into and along artery wall </li>...
Aortic Dissection <ul><li>Coarctation of the aorta is also a risk factor for aortic dissection </li></ul><ul><li>Coarctati...
Aortic Dissection <ul><li>Rate </li></ul><ul><ul><li>2 per 10,000 people </li></ul></ul><ul><ul><li>Can occur in anyone </...
Aortic Dissection <ul><li>Symptoms continued </li></ul><ul><ul><li>Decreased movement or sensation </li></ul></ul><ul><ul>...
Aortic Dissection & Rupture <ul><li>Life threatening condition </li></ul><ul><li>Likelihood of death in untreated individu...
Aortic Dissection & Rupture <ul><li>Aortic dissection can lead to </li></ul><ul><ul><li>Blood loss </li></ul></ul><ul><ul>...
Aortic Rupture <ul><li>Tear in the aorta </li></ul><ul><li>Can lead to exsanguination </li></ul><ul><li>Often with hemotho...
Aortic Dilation <ul><li>Aneurysm </li></ul><ul><li>Ballooning or widening of aorta </li></ul><ul><li>Due to weakness in wa...
Marfan Syndrome <ul><li>Hereditary disorder </li></ul><ul><ul><li>Autosomal dominant </li></ul></ul><ul><ul><li>But 30% sp...
Marfan Syndrome <ul><li>Features </li></ul><ul><ul><li>Tall </li></ul></ul><ul><ul><li>Thin </li></ul></ul><ul><ul><li>Lon...
Marfan Syndrome <ul><li>Features continued </li></ul><ul><ul><li>High arched palate </li></ul></ul><ul><ul><li>Long thin f...
Marfan Syndrome <ul><li>Cardiovascular features continued </li></ul><ul><ul><li>Aortic regurgitation </li></ul></ul><ul><u...
Marfan Syndrome <ul><li>Cardiac features continued </li></ul><ul><ul><li>At risk for dissecting aortic aneurysm </li></ul>...
Blood Vessel Layers <ul><li>Tunica intima </li></ul><ul><ul><li>Lines lumen </li></ul></ul><ul><ul><li>Endothelial cell la...
Blood Vessel Layers Continued <ul><li>Tunica Adventitia </li></ul><ul><ul><li>Loose connective tissue </li></ul></ul><ul><...
Normal Aorta Vs. Jugular Vein Note Aorta’s thick, highly structured tunica media
Layers of Aorta <ul><li>Elastic artery </li></ul><ul><li>Tunica media makes up most of vessel </li></ul><ul><ul><li>Many m...
Aortic Dissection Example <ul><li>In patient with Marfan syndrome </li></ul><ul><li>Just above aortic root </li></ul><ul><...
Aortic Dissection Example <ul><li>7 cm above aortic valve </li></ul><ul><li>Near the great vessels of aorta </li></ul><ul>...
Aortic Dissection Example <ul><li>Blood dissected proximally through the media </li></ul><ul><li>Hemopericardium resulted ...
Aortic Dissection Example <ul><li>Intimal tear </li></ul><ul><li>Created double lumen of aorta </li></ul><ul><li>Thrombus ...
Aortic Dissection Example Occurred through muscular wall (tunica media)
Aortic Dissection Example <ul><li>Right carotid compression from dissected blood </li></ul><ul><li>Blood dissected upward ...
Aortic Dissection <ul><li>Cross section of aorta </li></ul><ul><li>Thrombus of aortic lumen </li></ul><ul><li>From intimal...
Cystic Medial Necrosis <ul><li>Mucin stain of aortic wall </li></ul><ul><li>Typical in Marfan Syndrome </li></ul><ul><li>C...
Normal Pregnancy <ul><li>Normal physiological changes occur </li></ul><ul><li>These changes greatly affect the cardiovascu...
Cardiovascular Changes in Pregnancy <ul><li>Reasons </li></ul><ul><ul><li>Support new and growing tissues </li></ul></ul><...
Cardiovascular Changes in Pregnancy <ul><li>Blood changes </li></ul><ul><ul><li>Intravascular volume increases by 25-40% <...
Cardiovascular Changes in Pregnancy <ul><li>Blood changes continued </li></ul><ul><ul><li>Red blood cells increase </li></...
Cardiovascular Changes in Pregnancy <ul><li>Cardiac changes </li></ul><ul><ul><li>Begin around week 13 </li></ul></ul><ul>...
Cardiovascular Changes in Pregnancy <ul><li>Increased cardiac output continued </li></ul><ul><ul><li>Mainly due to increas...
Cardiovascular Changes in Pregnancy <ul><li>Heart rate increases </li></ul><ul><li>Blood pressure increases </li></ul><ul>...
Anatomy of Heart
Cardiac Tamponade
Cardiac Tamponade <ul><li>Ventricles compressed </li></ul><ul><li>Cannot fill and pump blood adequately </li></ul><ul><li>...
Scientific Method <ul><li>Observations </li></ul><ul><li>Hypothesis </li></ul><ul><li>Variables </li></ul><ul><li>Experime...
Observations <ul><li>25 to 50% of Turner syndrome patients have a cardiovascular malformation </li></ul><ul><li>Turner syn...
Observations <ul><li>The normal physiological changes of pregnancy place increased demands on the mother’s body, especiall...
Observations <ul><li>The cause of death for these women is aortic dissection or rupture </li></ul><ul><li>50% of all aorti...
Hypotheses <ul><li>Turner syndrome patients who turn to oocyte donation to alleviate infertility problems face the risk of...
Hypotheses <ul><li>Authors also stated that one objective of the study was to determine the pregnancy outcomes and rate of...
Variables <ul><li>The authors of this paper failed to compare a control group to the experimental group </li></ul><ul><li>...
Variables <ul><li>However, authors could have compared Turner syndrome patients who achieve and maintain pregnancy to the ...
Variables <ul><li>Authors also could have compared risk of death from aortic dissections and ruptures in non-pregnant Turn...
Experiments <ul><li>Literature searches using PubMed and MEDLINE to determine the number of US cases of deaths or cardiac ...
Experiments <ul><li>Survey ran from September 1, 2000 to July 31 2001 (10 months) </li></ul><ul><li>Each program was allow...
Experiments <ul><li>The questionnaire was designed to be easy to answer, consisting of 9 check-box style questions </li></...
Results <ul><li>Literature reviews revealed 4 deaths of Turner syndrome patients during or shortly after pregnancy </li></...
Results <ul><li>Literature review continued </li></ul><ul><ul><li>1 of the women had essential hypertension </li></ul></ul...
Results <ul><li>Literature review continued </li></ul><ul><ul><li>1998 3 rd woman developed aortic dissection during preg...
Results <ul><li>Literature review continued </li></ul><ul><ul><li>4 th revealed in study of pregnancy outcomes for patien...
Results <ul><li>Literature review concluded </li></ul><ul><ul><li>Screening revealed aortic dimensions within normal limit...
Survey Results <ul><li>52% of programs responded </li></ul><ul><li>146 Turner syndrome patients reported </li></ul><ul><li...
Survey Results
Survey Results
Survey Results <ul><li>146 patients seen </li></ul><ul><li>49% (72) were screened with echocardiogram </li></ul><ul><li>8%...
Survey Results <ul><li>2 of the screened patients were not treated with oocyte donation </li></ul><ul><ul><li>1 with compl...
Survey Results <ul><li>69% (101) of the 146 patients undergoing treatment became pregnant </li></ul><ul><li>Out of these 9...
Communications to the Scientific Community <ul><li>The authors estimate (by applying their numbers to some other assumptio...
Communications <ul><li>Specifically, they estimate that 4 deaths occurred in 200 possible donor oocyte pregnancies </li></...
Conclusions <ul><li>Authors state that the death rate could be smaller if the programs that did not respond treated more T...
Conclusions <ul><li>Furthermore, they speculate that deaths may not be reported because </li></ul><ul><ul><li>Doctors lost...
Conclusions <ul><li>Another likely possibility for higher death rates could be that only the centers treating Turner syndr...
Conclusions & Further Studies <ul><li>The other important findings of the study were that only half of the treated patient...
Conclusions & Future Studies <ul><li>Furthermore screening alone does not totally abolish the risk </li></ul><ul><li>Autho...
Thanks To <ul><li>Dr. Jay Ko, Univ. of Kentucky </li></ul><ul><li>Dr. Doris Baker, Univ. of Kentucky </li></ul><ul><li>T...
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Presented by Rebecca Singleton Turner Syndrome Overview

Published on: Mar 4, 2016
Source: www.slideshare.net


Transcripts - Presented by Rebecca Singleton Turner Syndrome Overview

  • 1. Presented by Rebecca Singleton
  • 2. Turner Syndrome Overview; What Is It? <ul><li>Birth defect, only seen in women </li></ul><ul><li>Congenital absence of X-chromosome </li></ul><ul><ul><li>If all cells affected </li></ul></ul><ul><ul><ul><li>X-monosomy (true 45 X genotype) </li></ul></ul></ul><ul><ul><ul><li>Most severe kind </li></ul></ul></ul><ul><ul><ul><li>Affects 60% of cases </li></ul></ul></ul><ul><ul><li>Or if some cells affected </li></ul></ul><ul><ul><ul><li>Mosaicism </li></ul></ul></ul><ul><ul><ul><li>Varying severity </li></ul></ul></ul><ul><li>Or X-chromosome defects </li></ul><ul><ul><li>1 normal X-chromosome </li></ul></ul><ul><ul><li>1 fragmented or structurally abnormal X-chromosome </li></ul></ul>
  • 3. Turner Syndrome Overview <ul><li>1 in 2000-2500 live female births </li></ul><ul><li>Not a hereditary disease, except in rare instances </li></ul><ul><li>Leads to sexual immaturity and generally infertility </li></ul>
  • 4. Turner Syndrome Genotype: 45 X; What Does It Look Like?
  • 5. Normal Gametogenesis: How Does It Happen? <ul><li>Spermatocytes are formed from sperm cell precursors </li></ul><ul><li>Contain 1 copy of each of 22 autosomes </li></ul><ul><li>Contain either an X or a Y </li></ul><ul><ul><li>In oogenesis, both ova would contain an X </li></ul></ul>
  • 6. Abnormal Gametogenesis Leading to Turner Syndrome: How Does It Happen? <ul><li>X or Y chromosome gets lost </li></ul><ul><li>Cell still has 22 normal autosomes </li></ul><ul><li>At least 1 X required for life </li></ul><ul><ul><li>Daughter receiving 1 X from mom and no X from dad can survive </li></ul></ul><ul><ul><li>Son receiving 1 Y from dad, no X from mom will not survive </li></ul></ul>
  • 7. Mosaics: How Do They Happen? Normal, fertilized egg Normal Mitosis X chromosome lost from developing embryo Resulting in 25% Turner Mosaic
  • 8. Turner Syndrome Phenotype: What Is the Distribution? Note: 98% infertile and 95% have ovarian failure
  • 9. Turner Syndrome Phenotype: What Is Affected? <ul><li>Affected Body Systems </li></ul><ul><ul><li>Lymphatics </li></ul></ul><ul><ul><li>Heart </li></ul></ul><ul><ul><li>Kidneys </li></ul></ul><ul><ul><li>Eyes </li></ul></ul><ul><ul><li>Ears </li></ul></ul><ul><ul><li>Skin </li></ul></ul><ul><ul><li>Bones </li></ul></ul><ul><ul><li>Reproductive </li></ul></ul>
  • 10. Turner Syndrome Phenotype <ul><li>Lymphatic Defects </li></ul><ul><ul><li>Contribute to </li></ul></ul><ul><ul><ul><li>Nail defects </li></ul></ul></ul><ul><ul><ul><li>Low hairline </li></ul></ul></ul><ul><ul><ul><li>Ear deformities </li></ul></ul></ul><ul><ul><ul><li>Webbed neck </li></ul></ul></ul><ul><ul><ul><li>Shield chest </li></ul></ul></ul>
  • 11. Nail Deformity <ul><li>Affects 70% of patients </li></ul><ul><li>Caused by peripheral lymphedema </li></ul><ul><li>Small, narrow, hyperconvex nails that are deeply inserted at an acute angle </li></ul>
  • 12. Webbed Neck <ul><li>Affects 25% of patients </li></ul><ul><li>Jugular lymph sacs fail to drain properly </li></ul><ul><li>Enlarge and form a sac, called cystic hygroma early in fetal development </li></ul><ul><li>Late in gestation, lymph problems are corrected, but loose folds of extra skin remain </li></ul>
  • 13. Cystic Hygroma <ul><li>Most concepti with 45 X spontaneously abort </li></ul><ul><li>15% of spontaneous abortions have a genotype of 45 X </li></ul>
  • 14. Other Lymphatic Defects <ul><li>Cystic hygroma also causes </li></ul><ul><ul><li>Low hairline </li></ul></ul><ul><ul><li>Low set ears </li></ul></ul><ul><li>Lymphedema also causes </li></ul><ul><ul><li>Shield shaped chest </li></ul></ul><ul><ul><li>Due to thoracic cage being stretched due to fetal edema </li></ul></ul>
  • 15. Cardiovascular Defects <ul><li>May result from defective lymphatics as well </li></ul><ul><li>Present in 1/3 of cases </li></ul><ul><li>Highest cause of death </li></ul><ul><li>Left side defects most common </li></ul><ul><ul><li>Coarctation of aorta </li></ul></ul><ul><ul><li>Bicuspid aortic valve </li></ul></ul><ul><ul><li>Aortic atresia </li></ul></ul>
  • 16. Renal Defects <ul><li>Usually benign </li></ul><ul><li>Most common horseshoe kidney </li></ul><ul><ul><li>10% </li></ul></ul><ul><ul><li>Greatest risk is UTI risk from blocked ureters </li></ul></ul><ul><li>Generally have normal renal function </li></ul>
  • 17. Eyes, Ears and Skin <ul><li>Eyes </li></ul><ul><ul><li>Strabismus </li></ul></ul><ul><ul><li>Ptosis </li></ul></ul><ul><li>Ears </li></ul><ul><ul><li>Acute, recurrent otitis media in infancy and childhood </li></ul></ul><ul><ul><li>Hearing disorders </li></ul></ul><ul><li>Skin </li></ul><ul><ul><li>Multiple nevi </li></ul></ul>
  • 18. Orthopedic Disorders <ul><li>Growth problems </li></ul><ul><ul><li>Delayed growth </li></ul></ul><ul><ul><li>Not uniform </li></ul></ul><ul><li>Small bones </li></ul><ul><ul><li>35% have short 4 th and 5 th metacarpals </li></ul></ul><ul><ul><ul><li>Lack of knuckles </li></ul></ul></ul><ul><li>Decreased bone mineral density </li></ul>
  • 19. Orthopedic Disorders <ul><li>Scoliosis in 12% of patients </li></ul><ul><li>Genus Valgus (knock knees) in 60% </li></ul><ul><li>Cubitis Valgus in 45% </li></ul><ul><li>Micrognathia (small chin) in 60% </li></ul><ul><li>High arched palate in 34% </li></ul><ul><li>Average adult height (not treated with GH) is 4’8” </li></ul><ul><ul><li>Average normal is 5’4” </li></ul></ul><ul><ul><li>After GH treatment height can be 4’10” to 5’ </li></ul></ul>
  • 20. Reproductive Defects <ul><li>Ovarian dysgenesis </li></ul><ul><ul><li>95% </li></ul></ul><ul><ul><li>Delayed or absent sexual development </li></ul></ul><ul><li>Primary amenorrhea common </li></ul><ul><li>12% spontaneous puberty </li></ul><ul><ul><li>Often estrogen production stops </li></ul></ul><ul><ul><li>Ovarian failure later </li></ul></ul><ul><ul><li>Risk of premature menopause </li></ul></ul>
  • 21. Chronic Problems <ul><li>Thyroid problems </li></ul><ul><ul><li>Hashimoto thyroiditis (autoimmune hypothyroidism) </li></ul></ul><ul><ul><li>35%, risk increases with age </li></ul></ul><ul><li>Diabetes </li></ul><ul><ul><li>Type II </li></ul></ul><ul><ul><li>2 times the risk of normal population </li></ul></ul><ul><li>High blood pressure </li></ul><ul><li>Osteoporosis </li></ul><ul><ul><li>10 times the risk of normal population </li></ul></ul><ul><li>Obesity </li></ul><ul><li>Infertility </li></ul><ul><ul><li>Less than 5% maintain menses </li></ul></ul><ul><ul><li>Spontaneous pregnancy rare </li></ul></ul>
  • 22. Turner Syndrome Phenotype: Example <ul><li>Short stature </li></ul><ul><li>Webbed neck </li></ul><ul><li>Shield-like chest </li></ul><ul><li>Edema of wrists and ankles </li></ul>
  • 23. Turner Syndrome Phenotype: Example <ul><li>Low hairline </li></ul><ul><li>Broad chest </li></ul><ul><li>Narrow hips </li></ul>
  • 24. Turner Syndrome Phenotype: Example <ul><li>Marked edema </li></ul><ul><li>Many times first indication of syndrome </li></ul><ul><li>Present in 1/3 of infants with Turner syndrome </li></ul><ul><li>Gets better with age </li></ul><ul><li>May flare up at puberty </li></ul>
  • 25. Turner Syndrome Phenotype: Example <ul><li>Generalized lymphedema </li></ul><ul><li>Loose skin folds at neck </li></ul><ul><li>Will later have webbed neck </li></ul>
  • 26. Reproductive Anatomy of Turner Syndrome <ul><li>Streak ovaries present </li></ul><ul><li>Long, thin bands of ovarian tissue </li></ul><ul><li>Taken from 55 year old </li></ul><ul><li>No ova ever present </li></ul>
  • 27. Anatomy of Heart
  • 28. Aortic Dissection <ul><li>Artery lining tears or is damaged </li></ul><ul><li>Blood leaks into and along artery wall </li></ul><ul><li>Extreme medical emergency </li></ul><ul><li>Death often occurs in minutes </li></ul><ul><li>May be associated with pregnancy </li></ul><ul><li>Can be due to collagen disorders, (Marfan syndrome) </li></ul><ul><li>Hypertension and atherosclerosis also risk factors </li></ul>
  • 29. Aortic Dissection <ul><li>Coarctation of the aorta is also a risk factor for aortic dissection </li></ul><ul><li>Coarctation of the aorta common in Turner syndrome </li></ul>
  • 30. Aortic Dissection <ul><li>Rate </li></ul><ul><ul><li>2 per 10,000 people </li></ul></ul><ul><ul><li>Can occur in anyone </li></ul></ul><ul><ul><li>Most often in men ages 40 to 70 </li></ul></ul><ul><ul><li>Usually high blood pressure and atherosclerosis contributing factors </li></ul></ul><ul><li>Symptoms </li></ul><ul><ul><li>Usually sudden </li></ul></ul><ul><ul><li>Chest pain (similar to a heart attack) </li></ul></ul><ul><ul><li>Cognitive changes </li></ul></ul>
  • 31. Aortic Dissection <ul><li>Symptoms continued </li></ul><ul><ul><li>Decreased movement or sensation </li></ul></ul><ul><ul><li>High anxiety </li></ul></ul><ul><ul><li>Pale, clammy skin </li></ul></ul><ul><ul><li>Increased heart rate </li></ul></ul><ul><ul><li>Thirst </li></ul></ul><ul><ul><li>Nausea and vomiting </li></ul></ul><ul><ul><li>Dizzy/faint </li></ul></ul><ul><ul><li>Breathing problems </li></ul></ul><ul><ul><li>Shock (may have increased or decreased blood pressure </li></ul></ul><ul><ul><li>Murmur, abnormal heart sounds </li></ul></ul>
  • 32. Aortic Dissection & Rupture <ul><li>Life threatening condition </li></ul><ul><li>Likelihood of death in untreated individuals in the first 48 hours is 1% per hour </li></ul><ul><li>Curable if repaired surgically before aortic rupture </li></ul><ul><li>Less than half with aortic rupture survive </li></ul>
  • 33. Aortic Dissection & Rupture <ul><li>Aortic dissection can lead to </li></ul><ul><ul><li>Blood loss </li></ul></ul><ul><ul><li>Thrombus </li></ul></ul><ul><ul><li>Inadequate blood supply past injury </li></ul></ul><ul><ul><li>Irreversible kidney failure </li></ul></ul><ul><ul><li>Stroke </li></ul></ul><ul><ul><li>Heart attack </li></ul></ul><ul><ul><li>Cardiac tamponade </li></ul></ul>
  • 34. Aortic Rupture <ul><li>Tear in the aorta </li></ul><ul><li>Can lead to exsanguination </li></ul><ul><li>Often with hemothorax </li></ul><ul><li>X-ray of chest full of blood (right side of patient) </li></ul>
  • 35. Aortic Dilation <ul><li>Aneurysm </li></ul><ul><li>Ballooning or widening of aorta </li></ul><ul><li>Due to weakness in wall of aorta </li></ul><ul><li>Increased risk of rupture </li></ul>
  • 36. Marfan Syndrome <ul><li>Hereditary disorder </li></ul><ul><ul><li>Autosomal dominant </li></ul></ul><ul><ul><li>But 30% sporadic cases </li></ul></ul><ul><ul><li>Spontaneous new mutation </li></ul></ul><ul><ul><li>Affects 2 per 10,000 people </li></ul></ul><ul><li>Affects connective tissue </li></ul><ul><ul><li>Skeletal </li></ul></ul><ul><ul><li>Cardiovascular </li></ul></ul><ul><ul><li>Eyes </li></ul></ul><ul><ul><li>Skin </li></ul></ul>
  • 37. Marfan Syndrome <ul><li>Features </li></ul><ul><ul><li>Tall </li></ul></ul><ul><ul><li>Thin </li></ul></ul><ul><ul><li>Long limbs </li></ul></ul><ul><ul><li>Spider like fingers (Arachnodactyly) </li></ul></ul><ul><ul><li>Chest defects (pectus excavatum or pectus carinatum) </li></ul></ul><ul><ul><li>Scoliosis </li></ul></ul>
  • 38. Marfan Syndrome <ul><li>Features continued </li></ul><ul><ul><li>High arched palate </li></ul></ul><ul><ul><li>Long thin face </li></ul></ul><ul><ul><li>Crowded teeth </li></ul></ul><ul><ul><li>Nearsighted </li></ul></ul><ul><ul><li>Dislocated lenses </li></ul></ul><ul><ul><li>Cardiovascular </li></ul></ul><ul><ul><ul><li>Dilatation (enlargement) of aortic root </li></ul></ul></ul>
  • 39. Marfan Syndrome <ul><li>Cardiovascular features continued </li></ul><ul><ul><li>Aortic regurgitation </li></ul></ul><ul><ul><ul><li>Aka aortic insufficiency or aortic valve prolapse </li></ul></ul></ul><ul><ul><ul><li>Due to weak valve </li></ul></ul></ul><ul><ul><ul><li>Blood flows back into left ventricle </li></ul></ul></ul><ul><ul><li>Prolapse of mitral valve </li></ul></ul><ul><ul><ul><li>Weak valve </li></ul></ul></ul><ul><ul><ul><li>Blood pushed back into left atrium </li></ul></ul></ul>
  • 40. Marfan Syndrome <ul><li>Cardiac features continued </li></ul><ul><ul><li>At risk for dissecting aortic aneurysm </li></ul></ul><ul><ul><li>Must be monitored during pregnancy </li></ul></ul><ul><ul><ul><li>Due to increase cardiovascular demands of pregnancy </li></ul></ul></ul><ul><ul><ul><li>Increased stress placed on heart and aorta </li></ul></ul></ul>
  • 41. Blood Vessel Layers <ul><li>Tunica intima </li></ul><ul><ul><li>Lines lumen </li></ul></ul><ul><ul><li>Endothelial cell layer </li></ul></ul><ul><ul><li>And subendothelial cell layer of loose connective tissue </li></ul></ul><ul><li>Tunica media </li></ul><ul><ul><li>Circular layers of smooth muscle cells </li></ul></ul><ul><ul><li>Thick in arteries </li></ul></ul><ul><ul><li>Also lots of elastic fibers </li></ul></ul>
  • 42. Blood Vessel Layers Continued <ul><li>Tunica Adventitia </li></ul><ul><ul><li>Loose connective tissue </li></ul></ul><ul><ul><ul><li>Contains Fibroblasts and collagen fibers </li></ul></ul></ul><ul><ul><li>Vaso vasorum </li></ul></ul><ul><ul><ul><li>Blood supply to the blood supply </li></ul></ul></ul>
  • 43. Normal Aorta Vs. Jugular Vein Note Aorta’s thick, highly structured tunica media
  • 44. Layers of Aorta <ul><li>Elastic artery </li></ul><ul><li>Tunica media makes up most of vessel </li></ul><ul><ul><li>Many membranes of elastic fibers in layers with circumferential smooth muscle </li></ul></ul><ul><li>Intima and media boundary not well defined </li></ul>
  • 45. Aortic Dissection Example <ul><li>In patient with Marfan syndrome </li></ul><ul><li>Just above aortic root </li></ul><ul><li>Extends across aorta </li></ul><ul><li>Hemopericardium and tamponade occurred within minutes </li></ul>
  • 46. Aortic Dissection Example <ul><li>7 cm above aortic valve </li></ul><ul><li>Near the great vessels of aorta </li></ul><ul><li>Atherosclerosis present </li></ul>
  • 47. Aortic Dissection Example <ul><li>Blood dissected proximally through the media </li></ul><ul><li>Hemopericardium resulted </li></ul><ul><li>Cardiac tamponade may be present due to the extreme hemorrhage </li></ul>
  • 48. Aortic Dissection Example <ul><li>Intimal tear </li></ul><ul><li>Created double lumen of aorta </li></ul><ul><li>Thrombus formation after limited dissection </li></ul><ul><li>Marked atherosclerosis present </li></ul>
  • 49. Aortic Dissection Example Occurred through muscular wall (tunica media)
  • 50. Aortic Dissection Example <ul><li>Right carotid compression from dissected blood </li></ul><ul><li>Blood dissected upward from aortic tear </li></ul><ul><ul><li>Can dissect upward toward carotids or downward toward coronaries </li></ul></ul><ul><ul><li>Therefore, symptoms may reflect those of a stroke or heart attack </li></ul></ul>
  • 51. Aortic Dissection <ul><li>Cross section of aorta </li></ul><ul><li>Thrombus of aortic lumen </li></ul><ul><li>From intimal tear followed by high pressure dissection of blood out through muscular wall to adventitia </li></ul>
  • 52. Cystic Medial Necrosis <ul><li>Mucin stain of aortic wall </li></ul><ul><li>Typical in Marfan Syndrome </li></ul><ul><li>Causes connective tissue weakness </li></ul><ul><li>Responsible for aortic dissection </li></ul><ul><li>Pink elastic fibers should be in parallel arrays </li></ul><ul><li>Instead interrupted by masses of blue mucinous material </li></ul>
  • 53. Normal Pregnancy <ul><li>Normal physiological changes occur </li></ul><ul><li>These changes greatly affect the cardiovascular system </li></ul>
  • 54. Cardiovascular Changes in Pregnancy <ul><li>Reasons </li></ul><ul><ul><li>Support new and growing tissues </li></ul></ul><ul><ul><li>Hormone changes affecting fluid dynamics (sodium and potassium metabolism) </li></ul></ul><ul><ul><ul><li>Total body water increases </li></ul></ul></ul><ul><ul><li>New blood vessel growth and increase in diameter of existing vessels </li></ul></ul>
  • 55. Cardiovascular Changes in Pregnancy <ul><li>Blood changes </li></ul><ul><ul><li>Intravascular volume increases by 25-40% </li></ul></ul><ul><ul><ul><li>Rises quickest in weeks 6-24 </li></ul></ul></ul><ul><ul><ul><li>Reaches max at 32 weeks and stays there </li></ul></ul></ul><ul><ul><ul><li>Does not return to normal until 4 weeks postpartum </li></ul></ul></ul>
  • 56. Cardiovascular Changes in Pregnancy <ul><li>Blood changes continued </li></ul><ul><ul><li>Red blood cells increase </li></ul></ul><ul><ul><ul><li>Overall increase still less than 1/3 that of total volume increase </li></ul></ul></ul><ul><ul><ul><li>Appears as “dilution anemia” </li></ul></ul></ul><ul><ul><ul><li>15% hematocrit drop </li></ul></ul></ul><ul><ul><ul><li>Does not return to normal until 8 weeks post partum </li></ul></ul></ul><ul><ul><li>Serum protein decreases </li></ul></ul><ul><ul><li>Serum lipids increase by 50% </li></ul></ul>
  • 57. Cardiovascular Changes in Pregnancy <ul><li>Cardiac changes </li></ul><ul><ul><li>Begin around week 13 </li></ul></ul><ul><ul><li>Normal changes often look like heart disease </li></ul></ul><ul><ul><li>Heart changes position </li></ul></ul><ul><ul><li>Heart increases in size </li></ul></ul><ul><ul><li>Biggest change is the largely increased cardiac output </li></ul></ul>
  • 58. Cardiovascular Changes in Pregnancy <ul><li>Increased cardiac output continued </li></ul><ul><ul><li>Mainly due to increased stroke volume </li></ul></ul><ul><ul><li>20-40% increase </li></ul></ul><ul><ul><li>Rises by 30% during contractions </li></ul></ul><ul><ul><li>Continues to rise during labor </li></ul></ul><ul><ul><li>Another 29% increase immediately after delivery </li></ul></ul>
  • 59. Cardiovascular Changes in Pregnancy <ul><li>Heart rate increases </li></ul><ul><li>Blood pressure increases </li></ul><ul><li>Decrease in venous return </li></ul><ul><li>Half of women develop murmurs </li></ul><ul><li>Extra systoles are common </li></ul><ul><li>Difficulty breathing common </li></ul>
  • 60. Anatomy of Heart
  • 61. Cardiac Tamponade
  • 62. Cardiac Tamponade <ul><li>Ventricles compressed </li></ul><ul><li>Cannot fill and pump blood adequately </li></ul><ul><li>Affects 2 per 10,000 people </li></ul><ul><li>Symptoms </li></ul><ul><ul><li>Chest pain; anxiety; dyspnea, tachypnea; faint; pallor; abdominal swelling; palpitations; very weak heart sounds </li></ul></ul><ul><li>Have to drain pericardium </li></ul>
  • 63. Scientific Method <ul><li>Observations </li></ul><ul><li>Hypothesis </li></ul><ul><li>Variables </li></ul><ul><li>Experiment </li></ul><ul><li>Results </li></ul><ul><li>Conclusion </li></ul>
  • 64. Observations <ul><li>25 to 50% of Turner syndrome patients have a cardiovascular malformation </li></ul><ul><li>Turner syndrome patients also have an inherent risk of death from aortic rupture or dissection </li></ul><ul><ul><li>10% of these individuals with aortic dilation, rupture or dissection had no risk factors (such as CV malformation) </li></ul></ul><ul><ul><li>Most of the patients with rupture or dissection have the causative factor of cystic medial necrosis, which is the same defect of Marfan syndrome </li></ul></ul>
  • 65. Observations <ul><li>The normal physiological changes of pregnancy place increased demands on the mother’s body, especially on the cardiovascular system </li></ul><ul><li>Marfan patients are cautioned about the increased stress that pregnancy places on the heart and aorta </li></ul><ul><li>Maternal death for Marfan patients without aortic defects is 5 to 15% </li></ul><ul><li>Death for those patients with aortic defects is 25 to 50% </li></ul>
  • 66. Observations <ul><li>The cause of death for these women is aortic dissection or rupture </li></ul><ul><li>50% of all aortic dissections in women of reproductive age occur in late pregnancy </li></ul><ul><li>Turner syndrome patients are encouraged to either adopt or seek IVF services for oocyte donation </li></ul>
  • 67. Hypotheses <ul><li>Turner syndrome patients who turn to oocyte donation to alleviate infertility problems face the risk of death, if pregnancy is achieved, through aortic dissection or rupture </li></ul><ul><li>Many clinicians are unaware of this risk, and fail to appropriately screen and monitor Turner syndrome patients </li></ul>
  • 68. Hypotheses <ul><li>Authors also stated that one objective of the study was to determine the pregnancy outcomes and rate of spontaneous abortion in this population </li></ul><ul><li>But a hypothesis regarding this objective was neither stated nor implied early in the paper </li></ul>
  • 69. Variables <ul><li>The authors of this paper failed to compare a control group to the experimental group </li></ul><ul><li>As Turner syndrome patients generally do not achieve pregnancy naturally, it would be implausible to compare patients undergoing oocyte donation versus those who do not utilize IVF </li></ul>
  • 70. Variables <ul><li>However, authors could have compared Turner syndrome patients who achieve and maintain pregnancy to the normal population of pregnant women (via oocyte donation) who die as a result of pregnancy and resultant aortic dissection or rupture </li></ul>
  • 71. Variables <ul><li>Authors also could have compared risk of death from aortic dissections and ruptures in non-pregnant Turner Syndrome patients of reproductive age to the patients achieving pregnancy through oocyte donation </li></ul>
  • 72. Experiments <ul><li>Literature searches using PubMed and MEDLINE to determine the number of US cases of deaths or cardiac events in the Turner syndrome population during pregnancy </li></ul><ul><li>Medical questionnaires regarding treatment and outcomes of Turner syndrome patients were faxed to medical directors of the 258 donor-egg programs listed in the 1997 National Summary and Fertility Clinic Reports </li></ul>
  • 73. Experiments <ul><li>Survey ran from September 1, 2000 to July 31 2001 (10 months) </li></ul><ul><li>Each program was allowed to respond by fax, phone or e-mail </li></ul><ul><li>Each program that did not respond to the initial invitation was faxed 2 more times </li></ul><ul><li>If still no response, the donor-egg coordinators or medical directors were contacted by phone and asked to respond then over the phone or by fax </li></ul>
  • 74. Experiments <ul><li>The questionnaire was designed to be easy to answer, consisting of 9 check-box style questions </li></ul><ul><li>Letters of intent, which assured anonymity to the responders, accompanied the questionnaires </li></ul><ul><li>Patient identifiers were neither used nor requested </li></ul>
  • 75. Results <ul><li>Literature reviews revealed 4 deaths of Turner syndrome patients during or shortly after pregnancy </li></ul><ul><li>2 women died in 1997 </li></ul><ul><ul><li>Sudden death in last trimester </li></ul></ul><ul><ul><li>From aortic dissection </li></ul></ul><ul><ul><li>Pregnant via oocyte donation </li></ul></ul>
  • 76. Results <ul><li>Literature review continued </li></ul><ul><ul><li>1 of the women had essential hypertension </li></ul></ul><ul><ul><li>She had been treated since childhood </li></ul></ul><ul><ul><li>Underwent preconception screening </li></ul></ul><ul><ul><ul><li>Revealed mildly dilated aortic root </li></ul></ul></ul><ul><ul><li>Second woman had no known risk factors </li></ul></ul>
  • 77. Results <ul><li>Literature review continued </li></ul><ul><ul><li>1998 3 rd woman developed aortic dissection during pregnancy </li></ul></ul><ul><ul><li>History of hypertension </li></ul></ul><ul><ul><li>24 weeks presented with epigastric pain </li></ul></ul><ul><ul><li>After misdiagnosis and worsening of condition found to have aortic dissection </li></ul></ul><ul><ul><li>Surgical repair </li></ul></ul><ul><ul><li>Died 3 months later from complications of ordeal </li></ul></ul>
  • 78. Results <ul><li>Literature review continued </li></ul><ul><ul><li>4 th revealed in study of pregnancy outcomes for patients with a history of aortic coarctation </li></ul></ul><ul><ul><li>50 women identified </li></ul></ul><ul><ul><ul><li>Some had surgical repair before or after pregnancy or both </li></ul></ul></ul><ul><ul><ul><li>Some had no repair </li></ul></ul></ul><ul><ul><ul><li>1 woman died </li></ul></ul></ul><ul><ul><ul><ul><li>Only patient with Turner syndrome </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Had surgical repair at 4 years old </li></ul></ul></ul></ul><ul><ul><ul><ul><li>No known history of hypertension </li></ul></ul></ul></ul>
  • 79. Results <ul><li>Literature review concluded </li></ul><ul><ul><li>Screening revealed aortic dimensions within normal limits </li></ul></ul><ul><ul><li>Died at 36 weeks gestation </li></ul></ul><ul><ul><li>Aortic dissection </li></ul></ul><ul><ul><li>Autopsy revealed aortic cystic medial degradation </li></ul></ul><ul><ul><li>Oocyte recipient </li></ul></ul><ul><ul><ul><li>Conceived triplets </li></ul></ul></ul><ul><ul><ul><li>Reduced to twins at 12 weeks </li></ul></ul></ul>
  • 80. Survey Results <ul><li>52% of programs responded </li></ul><ul><li>146 Turner syndrome patients reported </li></ul><ul><li>None died of aortic complications resulting from pregnancy </li></ul>
  • 81. Survey Results
  • 82. Survey Results
  • 83. Survey Results <ul><li>146 patients seen </li></ul><ul><li>49% (72) were screened with echocardiogram </li></ul><ul><li>8% (6) of these had an abnormality </li></ul><ul><ul><li>5 out of these 6 had aortic problems </li></ul></ul><ul><ul><ul><li>2 had unspecified aortic abnormalities </li></ul></ul></ul><ul><ul><ul><li>1 had coarctation </li></ul></ul></ul><ul><ul><ul><li>1 had bicuspid aortic valve </li></ul></ul></ul><ul><ul><ul><li>1 had bicuspid aortic valve with aortic regurgitation and dilatation of ascending aorta </li></ul></ul></ul><ul><ul><ul><li>1 had mitral valve regurgitation </li></ul></ul></ul>
  • 84. Survey Results <ul><li>2 of the screened patients were not treated with oocyte donation </li></ul><ul><ul><li>1 with complex findings </li></ul></ul><ul><ul><li>1 died of a dissecting aorta before undergoing treatment </li></ul></ul>
  • 85. Survey Results <ul><li>69% (101) of the 146 patients undergoing treatment became pregnant </li></ul><ul><li>Out of these 94 resulted in a live birth </li></ul><ul><ul><li>Spontaneous abortion was only 6% or 7 cases </li></ul></ul><ul><li>17% (17) multiple gestations occurred </li></ul><ul><li>100% of these resulted in at least 1 live born baby </li></ul>
  • 86. Communications to the Scientific Community <ul><li>The authors estimate (by applying their numbers to some other assumptions) that the death rate of Turner syndrome patients who achieve pregnancy through oocyte donation to be 2% </li></ul><ul><li>This number is based on the 4 deaths found in the literature search out of an estimated 194 successfully treated patients (extrapolated from the fact that 101 pregnancies were achieved in 52% of the nation’s programs) </li></ul>
  • 87. Communications <ul><li>Specifically, they estimate that 4 deaths occurred in 200 possible donor oocyte pregnancies </li></ul><ul><li>They estimated that the 48% of programs that did not respond had similar success rates (or 93 more pregnancies) </li></ul>
  • 88. Conclusions <ul><li>Authors state that the death rate could be smaller if the programs that did not respond treated more Turner syndrome patients </li></ul><ul><li>However, they speculate that the death rate is actually higher </li></ul><ul><ul><li>Note that no deaths were actually reported </li></ul></ul><ul><ul><li>May reflect an over tendency to underreport events </li></ul></ul>
  • 89. Conclusions <ul><li>Furthermore, they speculate that deaths may not be reported because </li></ul><ul><ul><li>Doctors lost contact with the patients if patients were seen at high-risk centers as a result of their condition </li></ul></ul><ul><ul><li>IVF centers fear lawsuits, and are tight-lipped </li></ul></ul>
  • 90. Conclusions <ul><li>Another likely possibility for higher death rates could be that only the centers treating Turner syndrome patients did respond </li></ul><ul><li>This would cause the death rate to be 4 per 101 patients, or about 4% </li></ul>
  • 91. Conclusions & Further Studies <ul><li>The other important findings of the study were that only half of the treated patients were screened for cardiovascular defects </li></ul><ul><li>Guidelines for such screenings are not widely reported in reproductive literature, but are present in pediatric literature </li></ul><ul><li>Now reproductive specialists need to be made aware of these procedures </li></ul>
  • 92. Conclusions & Future Studies <ul><li>Furthermore screening alone does not totally abolish the risk </li></ul><ul><li>Authors state that counseling should be made available for Turner syndrome patients </li></ul><ul><li>There is even debate about the screening tools used: echo or MRI? </li></ul><ul><li>Authors further recommend a national registry for Turner syndrome patients and ASRM guidelines for treatment </li></ul>
  • 93. Thanks To <ul><li>Dr. Jay Ko, Univ. of Kentucky </li></ul><ul><li>Dr. Doris Baker, Univ. of Kentucky </li></ul><ul><li>The Department of Clinical Sciences, Univ. of Kentucky </li></ul>

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