Genetic Syndromes

1. Genetic Syndromes Chromosomes Sex Linked Syndromes Gene Defects Development of Young Children with Disabilities#872.514 (61)Carol Ann Heath

2. CHROMOSOMAL ABNORMALITIES

3. What is a Trisomy? • A chromosomal anomaly characterized by the presence of an extra chromosome in the cells • A trisomy occurs when there are 47 chromosomes instead of 46 • A partial trisomy occurs when just part of an extra chromosome attaches to another

4. Trisomy continued • Mosaic trisomy occurs when the extra chromosome material is not present in every cell • The most common known trisomies are: • Trisomy 21 (Down syndrome) • Trisomy 18 (Edward’s syndrome) • Trisomy 13 (Patau’s syndrome)

5. Trisomy 21: Down syndrome • Extra 21st chromosome; 47 chromosomes in each cell • 1/800 births • Approximately 5,000 children with Down • syndrome born each year in U.S. • 1% chance of reoccurrence • Life expectancy: approximately 55 years

6. Down syndrome • 96% of children with Down syndrome have the extra chromosome 21 • 4% have either a translocation (attached to or incorporated into another chromosome in the egg or sperm) or a form called “Mosaic” in which not all cells affected. • Mosaic children may be less delayed

7. Prevalence • Prevalence increases with maternal age: • 29 years and younger 1/1500 • 30-34 years 1/800 • 35-39 years 1/270 • 40-44 years 1/100 • over 45 years 1/50

8. Physical Characteristics • Hypotonia short neck • oval-shaped eyes (excess skin) • epicanthal folds • single palmar creases • small nose • flattened nasal bridge • small oral cavity • small ears that may fold slightly at top

9. Health problems associated with Down syndrome • 40-50% have congenital heart defects • Respiratory problems, especially upper respiratory infections • Eye and ear problems including hearing loss • Thyroid problems • Cervical spine abnormalities • Gastrointestinal problems

10. Down syndrome continued • Most have some degree of mental retardation ranging from mild to severe. • Average person functions in mild to moderate range. • Education in public schools • Perform daily living skills independently • Can marry and have children (rare for men) • Women have 50% their child will have DS

11. Development • Better prognosis due to: • better health care • early intervention • more normal family and social experiences • better educational opportunities • more positive social attitudes

12. Development continued • Social and emotional development in infancy delayed, they progress in the first year is essentially normal. • Hypotonia delays motor skills which restricts their early experiences. • Visual exploration and eye-contact delayed in first year.

13. Development continued • Expressive language skills delayed • May be able to sign words before verbalizing them • 3/4 children have speech production problems • 4/5 may experience some degree of hearing loss (fluctuating caused by o.m.)

14. Development continued • Many children have auditory-perceptual impairment (tree/cheese) • At risk for dyspraxia-inability to perform coordinated movements

15. Benefits of sign language • A way of teaching speech and language • Method of communicating and expression • Develop comprehension of speech

16. Assisting with Language • Sign language • computers • open/closed questions • role play • synthesized speech

17. Reading • Most early reading books contain too little text and text that is too complex • Reading single words first: • matching • selecting • naming

18. Trisomy 13 • Sometimes referred to as Patau Syndrome • Described in 1657, etiology not discovered until 1960 by Dr. Klaus Patau • Extra 13th chromosome which results in significant multiple defects in major organ systems • Brain most severely affected • Many born blind, deaf, no sense of smell

19. Trisomy 13 • 1/8000 births • Median survival is 2.5 days • 82% die within the first month • 5% survive first 6 months • Those surviving longer have severe mental defects, seizures, and failure to thrive • Only 1 adult known to survive to age 33

20. Abnormalities • 80% heart defect • 60-80% cleft lip, cleft palate or both • Found in 50% or more patients: • central nervous system hearing • cranium eyes • skin hands and feet • skeletal genitalia

21. Etiology • Maternal age has been a factor with occurrence • Chance of recurrence is thought to be low • Trisomy 13 mosaicism usually show a less severe clinical phenotype, survival may be longer, and mental deficiency variable

22. Trisomy 18 • Also known as Edward’s syndrome • Discovered in 1960 by Dr. John Edwards • Caused by an extra 18th chromosome • It is the second most common multiple malformation syndrome • 1/6,600 births • Affects females 3:1

23. Trisomy 18 • 50% die within first week • Only 5-10% survive the first year as “severely mentally defective individuals” • 10 children over the age of 10 reported • Most unable to walk and language limited, but some older children who survive may interact and relate to family members.

24. Abnormalities • Growth deficiency • congenital anomalies of the heart, lung, kidneys, and diaphragm • increased muscle tone • small mouth and jaw • mental deficiency • microcephaly

25. Abnormalities continued • Low set malformed ears • small pelvis, limited hip abduction • underdeveloped nails • underdeveloped or absent thumbs • abnormal genitalia • episcanthal folds

26. Etiology • Maternal age contributing factor to occurrence • 1% chance of recurrence • Moscaicism leads to partial clinical expression, longer survival and various degrees of variations

27. Sex Linked • Abnormality in the overall number of chromosomes for X and Y • Male has one X and One Y • Female has two X

28. Disorders • Turner syndrome: female abnormality • Female has only one X, total of 45, not 46 chromosomes, resulting in XO pattern • Only case in which too few chromosomes can develop into an embryo and survive • 1/5000 female births

29. Turners • Very short <5 ft • Lowered hairline, broad chest and short neck • Ovaries do not function normally • IQ in typical range with learning disabilities, particularly visual-perceptual and mathematics

30. Klinefelter syndrome • Males has extra X chromosome, resulting in 47 • Pattern of XXY • 1/500 males • Taller and thinner; underdeveloped secondary sex traits; decreased hormone level • Language delays; normal adulthood

31. Chromosome deletions • Sometimes genetic material is missing from a chromosome. These chromosomes are said to have “deletions”. • Interstitial deletions occur when a chromosome has broken, genetic material has been lost, and the chromosome arms rejoin • Larger deletions lead to death

32. Chromosomal Errors • Deletion #22q11.2 syndrome • Williams syndrome • Fragile X • Cri du chat

33. Cri du chat syndrome • First described in 1963 by Lejeune • Syndrome associated with deletion of the short arm of chromosome5 • Deletion can vary in size from extremely small (involving only one band) to the entire short arm • Majority of children die in early childhood, some survive into adulthood with low IQ

34. Prevalence • One of the most common deletion syndromes • Varying between 1/20,000 and 1/50,000

35. Abnormalities • Low birth weight 72% • Slow growth 100% • cat-like cry 100% • hypotonia 78% • mental deficiency 100% • microcephaly 100% • strabismus 61%

36. Abnormalities continued • Round face 68% • epicanthal folds 85% • Low set and/or poorly formed ears 57% • congenital heart disease 30%

37. Development • As babies, unusually squirmy • Cat-like cry that becomes less prominent with age • With special schooling and supportive home environment, some children have attained social and psychomotor skills of a 5 to 6 year old • 50% had vocabulary adequate for communication

38. William syndrome • Described in 1961 by Williams • deletion of one allele located within chromosome subunit 7q11.23 • 1/20,000 births

39. Abnormalities • Mild growth deficiency • mild microcephaly • small upturned nose • long philtrum • epicanthal folds • cardiac anomalies • joint limitations

40. Performance • Average IQ is 56 (range 40-80) • Hoarse voice • Hypersensitive to sound • Mild neurologic dysfunction • Poor coordination • Decreased perceptual and motor function • Language ability much greater than cognitive ability

41. Development • Infancy: feeding problems, colicky, fretful • Childhood: outgoing, no fear of strangers, strong interest in others • 2/3 of children: difficult temperament, more negative moods, increased activity, distractible, less persistence, and low threshold arousal

42. Development continued • As adults: progressive medical problems • Most live with parents or in group home • Sudden death reported in a number of children

43. Deletion #22q11.2 syndrome • Previously known as DiGeorge syndrome • 1 out 5000 births • Common cause of genetic heart malformation • Facial anomalities: small mouth, narrow eyes, bulbous nose, palate • Immune deficiency • Typical cognitive ranges with learning disabilities, particularly in math

44. Fragile X Syndrome

45. Mental Impairment • Females: • learning disabled in math • exceptional with reading and spelling • 1/3 have mental disabilities similar to those associated with schizophrenia • Males: • process information in simultaneous fashion • Sees whole in order to understand the parts

46. Speech and Language • Rapid bursts • Echolalic • Perseveration most difficulty for males • Talking inappropriately • One topic • Speech problems made worse if anxious

47. Behavioral Problems • ADHD • Temper tantrums • Mood swings • Aggression • Strong reaction to change in environment • Sensory integration • Autistic like behaviors

48. Medical Problems • At greater risk for otitis media • Myopia • “Lazy eye” • Orthopedic difficulties related to flat feet and joint laxity • 20% of males prone to seizures • Digestive disorders

49. Education • Early Intervention • Mainstreaming • Occupational therapy • Speech therapy • Physical therapy • Visual devices

50. Fragile X • Identified by a break or weakness on the long arm of the X chromosome • FMR-1 • X linked • “Genetic anticipation” • Testing for Fragile X