1. Turner Syndrome Based on: BRS, Big Picture, First Aid, Secrets, Rapid Review, Essentials of Rubin’s

2. Genetics MC sex chromosome abnormality in females Complete or partial X monosomy – Distribution is roughly half-and-half Usually a mosaic of 45,X/46,XX karyotype – Missing X is usually father’s – Less common mosaic: 45,X/46,XY Risk of gonadoblastoma

3. Genetics Less commonly caused by: – 45,XO karyotype 99% miscarriage rate Note: no extra chromosomes  no Barr body – Chromosome structure abnormalities 1 in 5000 live births No correlation with maternal age SHOX growth gene stays active on both chromosomes  deletion = short stature

4. Pathophysiology Decreased estrogen & progesterone Increased pituitary gonadotropins – 2/2 loss of feedback inhibition Normal GH and IGF-1

5. Findings Lots!!! Streaked ovaries – 2/2 accelerated loss of oocytes by age 2  all gone – Leads to amenorrhea (Turner = MC cause of) Menopause before menarche – most common initial complaint

6. Findings Ovarian dysgerminoma – Recall that Klinefelter males can get seminomas – Gross and microscopic appearance of ovarian dysgerminoma is very similar to seminoma

7. Findings Short stature (95%) – 2/2 SHOX gene deletion Shield chest Widely spaced nipples Wide carrying angle Low posterior hairline

8. Findings Lymphedema Cystic hygroma Webbed neck Multiple pigmented nevi Nail dysplasia

9. Findings Small mandible Prominent ears Epicanthal folds

10. Findings Kidney abnormalities – Horseshoe kidney – Malrotation

11. Findings Heart abnormalities (50%) – Hypoplastic left heart Major cause of infant death – Coarctation of the aorta – Bicuspid aortic valve 1/3 of patients

12. Findings Congenital pyloric stenosis – Projectile nonbilious vomiting – Olive-shaped mass Autoimmune hypOthyroidism

13. Recap - Findings Sexual infantilism – Amenorrhea, sterility, dysgerminoma MSK/derm – Dwarfism, cubitus valgus, facial anomalies, nevi Lymphatic – Lymphedema, webbed neck, cystric hygroma Heart – Hypoplastic L heart, coarctation of/bicuspid aorta Kidney – Horseshoe, malrotation Others: pyloric stenosis, Hashimoto thyroiditis

14. Prognosis Excellent when treated with GH, estrogen Usually normal intelligence Mosaic forms cause milder symptoms and may even be fertile Risk of primary hypertension – associated with aortic dissection  death

15. A thousand more words…

16. Klinefelter Syndrome

17. Genetics

18. Usually caused by maternal nondysjunction – Occurs during meiosis I of oogenesis – 47 chromosomes – XXY karyotype Less commonly due to mosaicism – 46,XY – 47,XXY

19. Pathophysiology The X chromosome carries genes for: – Androgen receptors Used by testosterone – Testis function – Brain development – Growth The androgen receptor (AR) gene contains CAG trinucleotide repeats

20. Pathophysiology Recall that testosterone mediates its function through the androgen receptor – Testosterone interacts best with ARs that have the least CAG repeats – More CAG repeats = less testosterone action KS causes inactivation of the X chromosome with the shortest CAG repeats – All you have left are the bad androgen receptors

21. Pathophysiology Result: hypogonadism – Decreased testosterone – Increased FSH and other pituitary gonadotropins Mechanism – Dysgenesis of seminiferous tubules –  decreased inhibin –  increased FSH

22. Pathogenesis Testicular volume decreases at puberty Histology – Fibrosis of seminiferous tubules – Absence of spermatogenesis – Loss of Sertoli cells – Prominence of Leydig cells Decreased Sertoli cells leads to  FSH – Increased FSH increases aromatase Aromatase converts testosterone  estradiol

23. Findings Usually undiagnosed until puberty Developmental delay Eunuchoid body shape Atrophic testes Sterility

24. Findings Long legs – 2/2 delayed fusion of epiphyses Gynecomastia Decreased body hair – Female hair distribution Hair does not extend from mons to umbilicus

25. Findings Cardiovascular abnormalities – Mitral valve prolapse 50% of adults Endocrine abnormalities – Increased risk of type 2 DM Higher risk of metabolic syndrome

26. Lab findings

27. Prognosis Intelligence is usually low-normal – if not, mental retardation is proportional to number of X chromosomes Higher chance of autoimmune disease – SLE, rheumatoid arthritis, Sjögren, osteoporosis

28. Prognosis Testosterone tx virilizes but still no fertility Higher risk of testicular neoplasms 20x increased risk of breast cancer

29. A thousand more words…