CYTOGENETIC DISORDERS

1. Dr. KIRAN H S ASSITNT PROFESSOR PATHOLOGY, YMC CYTOGENETIC DISORDERS

2. DOWNS SYNDROME • KLINEFELTERS SYNDROME • TURNERS SYNDROME

3. DOWNS SYNDROME

4. Introduction Down syndrome is a condition in which a person has an extra chromosome. Chromosomes are small “packages” of genes in the body.

5. CYTOGENETIC DISORDERSAFFECTING AUTOSOMES • Down syndrome- trisomy 21 a common cause of mental retardation • 47 chromosomes- in 95% 0f cases • In 4% of cases of down syndrome, the chromosome no is normal but with extrachromosomal material as translocation • Trisomy is due to meiotic nondisjunction

6. History Named after a physician, “John Langdon Down” in 18th century. Described as Mongoloid child of European parentage-”Mongolism” In 1959 a French doctor, named “Jerome Lejeune”, discovered it was caused by the inheritance of an extra chromosome 21. Also known as “trisomy 21”

8. Types of Down syndrome : Trisomy 21 - 95 % Translocation Down syndrome- 3% Mosaic Down syndrome – 2%

9. Risk factors : 1.Advancing maternal age – usually women of age 35 and above. 2.Mothers who already have one child with Down syndrome. 3.Parents who are carriers of the genetic translocation for Down syndrome.

10. Clinical features Extremities Shortbroad hands Short fifth finger Incurved fifth finger Transverse palmer crease Space between first and second toe Head and neck Brachycephaly Up-slanting palpebral fissures Epicanthal folds Brushfield spots Flat nasal bridge Folded or dysplastic ears Open mouth Protruding tongue Short neck Excessive skin at the nape of neck

11. Decreased muscle strenghth. Hypotonia Hyperflexibility Joint laxity Vitamin D defficiency Decreased bone mineral density.

14. Other Health-related problems • Cardiovascular problems ventricular septaldefect, atrial septal defect, patent ductusarteriosus • Endocrine problems • thyroid problems, diabetes mellitus • Gastrointestinal problems • duodenal, esophageal and anal atresia, Hirschprung’s disease • Haematological problems • Acute leukemia, transient myeproliferativedisease • Neurological problems • Epilepsy, severe behavioral problems, Alzheimer’s, memory problems

15. Other problems: • Sleep problems • Sleep apnoea, other sleep disturbance • Skeletal problems • Flat foot, atlantoaxial subluxation • Visual problems • Refractive disorder, squint, nystagmus • Hearing problems • Hearing loss, conductive hearing loss, chronic otitis media • Obesity and nutrient deficiency- Malabsorption (probably linked with celiac disease) due to intestinal damage • Some has lack of vitamin B12, folic acid and zinc • Need for antioxidants i.e. vitamin E

16. Diagnosis: 1 Prenatal screening Ultra sound Blood test Biochemical test Maternal serum screening 2.Diagnostic test Amniocentesis Villus Sampling

18. Management: 1.Growth – Measurements should be plotted on the appropriate growth chart for children with DS. This will help in prevention of obesity and early diagnosis of celiac disease and hypothyroidism. 2. Cardiac disease – All newborns should be evaluated by cardiac ECHO for CHD in consultation with pediatric cardiologist. 3. Hearing – Screening to be done in the newborn period, every 6 months until 3 yrs of age and then annually. 4. Eye disorders - An eye exam should be performed in the newborn period or at least before 6 months of age to detect strabismus, nystagmus, and cataracts.

19. Goals of PT. • Minimize the development of the compensatory movement patterns that children with Down syndrome are prone to develop. • Promote achievement of gross motor skills such as sitting,crawling and standing. • Improve independence in functional activities. • Improve muscle strength,posture and balance. • Improve confidence and socialization with peers through improved motor skills. • Reduce the risk of secondary joint problems in later life as a result of lax ligaments.

21. TRISOMY 21

22. TRISOMY 21(DOWN SYNDROME)

23. DOWN SYNDROME • 40% of cases have congenital heart disease. • 10 – 20 fold risk of acute leukemia – all or aml. • Above 40 years of age all develop alzheimers disease.

24. DOWN SYNDROME • Abnormal immune response - predispose to infection • Improved medical care- increased longeivity • 80% survive to 30 years or beyond

25. Klinefelter syndrome

26. Klinefelter syndrome • Individuals with Klinefelter syndrome have at least two X chromosomes and at least one Y chromosome. (XXY)

27. 47, XXY and XXY syndrome Because of the extra chromosome, individuals with the condition are usually referred to as : 47,XXY XXY Males = This chromosome constitution (karyotype) exists in roughly between 1:500 to 1:1000 live male births (XXY)

28. Cause • The extra X chromosome is retained because of a nondisjunction event during: • Meiosis I (gametogenesis) • Meiosis II in females (XXY)

29. Signs and symptoms • Signs and symptoms of Klinefelter syndrome vary by age (XXY)

30. Babies: Signs and symptoms • Weak muscles • Slow motor development — taking longer than average to sit up, crawl and walk • Delay in speaking • Quiet, docile personality • Problems at birth, such as testicles that haven't descended into the scrotum (XXY)

31. Boys and teenagers: Signs and symptoms • Enlarged breast tissue (gynecomastia) • Weak bones • Low energy levels • Shyness • Difficulty expressing feelings or socializing • Problems with reading, writing, spelling or math • Attention problems • Taller than average stature • Longer legs, shorter torso and broader hips compared with other boys • Absent, delayed or incomplete puberty • After puberty, less muscular bodies and less facial and body hair compared with other teens • Small, firm testicles • Small penis (XXY)

32. Men: Signs and symptoms • Infertility • Small testicles and penis • Taller than average stature • Weak bones • Decreased facial and body hair • Enlarged breast tissue • Decreased sex drive or sexual problems

33. Diagnosing Klinefelter Syndrome • The greatest chances to make Klinefelter’s diagnosing are in following times of life: • Before or shortly after birth • Early childhood • Adolescence • Adulthood. For males in which Klinefelter syndrome is suspected, a special blood test is recommended to confirm the Klinefelter syndrome diagnosis. (XXY)

34. Tests • Blood test: • Blood test called a karyotype and is the standard diagnostic method • Test looks at a person's chromosomes • Prenatal Testing: • many males have been diagnosed through amniocentesis or chorionic villus sampling (CVS) • In amniocentesis, a sample of the fluid surrounding the fetus is withdrawn • CVS is similar to amniocentesis. The procedure is done in the first trimester (during the fist three month of pregnancy, it’s important to establish a foundation of good health) and the fetal cells needed for examination are taken from the placenta (XXY)

35. Amniocentesisprocedure

36. Chorionic villus sampling (CVS)

37. Treatment • Testosterone treatment should begin at puberty: • can normalize body proportions and promote development of normal secondary sex characteristics • but does not treat infertility, gynecomastia and small testes (XXY)

38. CYTOGENETIC DISORDERS AFFECTING SEX CHROMOSOMES KLINEFELTERS SYNDROME • Common form of male hypogonadism which develops when there are at least 2 x chromosomes and one or more y chromosomes. • Most patients are karyotype 47, xxy • Non disjunction of sex chromosomes during meiosis.

39. KLINEFELTERS SYNDROME • Decreased serum testosterone level. • Increased urinary gonadotropin level.

40. KLINEFELTERS SYNDROME

41. KLINEFELTERS SYNDROME

42. KLINEFELTERS SYNDROME

43. KLINEFELTERS SYNDROME

44. BARR BODY

45. TURNERS SYNDROME

46. TURNER SYNDROME • Primary hypogonadism in phenotypic females • Results from partial or complete monosomy of x chromosome.

47. Agenda • Definition • Diagnosis • Symptoms • Treatment

48. History • Named after Henry Turner, the endocrinologist who described this condition in 1938. • He described 7 patients between the ages of 15 and 23, who were referred to him for dwarfism and lack of sexual development

49. What is Tuner’s Syndrome? A genetic disorder in girls caused by a missing or defective X (female) chromosome.

50. How does it Occur? • The human cells have 22 pairs of chromosomes and 1 pair of sex chromosomes (called X &Y). A female usually has XX chromosomes whereas a male has XY chromosomes. • These sex chromosomes determine the gender of a person, the height as well as development of sexual organs. • During mitosis only one X chromosome transfers to the egg for a female baby.