1. Chromosomal Anomalies
Detectable using a karyotype or FISH
Common at conception (60% of first trimester spontaneous abortions are chromosomal anomalies)
About 1/200 births (all types)
Maternal Age (especially in Down’s)

2. Down Syndrome Extra chromosome 21 material Most frequent = trisomy 21
Strong effect of maternal age

3. Down Syndrome: Signs & Symptoms
Physical
Characteristic facial appearance
Many systems affected—neurological, sensory, GI, cardiovascular, endocrine, dental
Unusual dermatoglyphics
Very high risk of Alzheimer’s
Behavioral
Mild to moderate intellectual deficiency and developmental delays (marked variable expressivity)
About 1/5 can be employed
Fewer behavioral problems given level of ID

5. Erik Nichols and mother, St. Petersburg, FL

6. Erik Nichols, 21, and his sister, 17-year-old Lindsey, on their graduation from high school.
(Saint Petersburg, FL)

7. James Webster and mother, Anne

8. Trisomy 21 Karyotype

9. Turner Syndrome Loss of a sex chromosome Karyotype = 45, XO
Phenotypically female

10. Turner’s Syndrome Background: Described in 1938 by Henry Turner
Cause isolated in 1960 (loss of one/part of one sex chromosome)
Physical Symptoms:
Short Stature (mean height < 5 feet)
Failure to develop secondary sex characteristics
Maldeveloped Ovaries (infertility; high risk of ovarian cancer)
Variety of medical problems: cardiovascular, kidney, pancreas, skeletal, thyroid: MARKED VARIABLE EXPRESSIVITY
Minor physical anomalies: webbed neck, low set ears, puffy hands and feet: MARKED VARIABLE EXPRESSIVITY
Behavioral Symptoms:
Normal intelligence
Normal personality (problems of self-esteem and body image may be associated with physical anomalies)
Lowered spatial-visualization and quantitative reasoning
? Higher stereotypical feminine interests

13. Turner’s Syndrome Karyotype

14. XYY Karyotype

15. Chromosomal Microdeletions
Large deletion but too small to be seen in a karyotype (several megabases and involving several genes)
FISH (fluorsescent in situ hybridization) used to detect the syndrome
Prevalence = 1/10k to 1/100k births
Most caused by de novo mutations (new mutation in sperm or egg)

16. Williams Syndrome Physical Behavioral Cause
Characteristic facial features (small, upturned nose, wide mouth small chin  “elfin” appearance)
Large number of medical problems
Behavioral
Intellectual deficiency mostly on performance but wide wide variable expressivity—some are above average on IQ
Developmental delays, learning disabilities, ADD
Very high sociability (talk to and hug strangers), engaging & charming personality
Verbal communication high
Fondness for music (treated with music therapy)
Cause
Microdeletion in 7q11.23
Involves up to 2 dozen genes

17.
comments-musical-potential-people-williams-syndrome
Ella Grace Larson. From

18. Dutra et al. (2011) Clinics, 66, 6, Sao Paulo

19. FISH: Williams Syndrome
Fluorescent in situ hybridization

20. Williams Syndrome Intriguing Questions:
Usually, deleting genetic material reduces behavioral capacity, so …
How does a deletion increase sociability and reduce fear of strangers?
How does a deletion influence an affinity for music?

21. Chromosomal Microdeletions: Prader-Willi and Angelman Syndromes

22. Prader-Willi Syndrome
Gene imprinted (turned off)
Gene not imprinted (turned on)
Maternal DNA
Paternal DNA D e l t d
Prader-Willi Syndrome D e l t d
Angelman Syndrome

23. http://www. ncbi. nlm. nih. gov/books/bv. fcgi. tool=bookshelf&call=bv

25. Prader-Willi Syndrome
Cause:
Usually caused by micro deletion in region q11-13 of the paternally transmitted chromosome 15.
Several genes in this region are genomically imprinted in the maternal chromosome.
Hence, if there is a paternal deletion in this region, there are no active genes.
Symptoms:
Short stature
Mental retardation, learning difficulties
Decreased muscle tone
Hypogonadism
Emotional lability
Unregulated appetite or hyperphagia ( obesity)

26. Prader Willi Syndrome

27. Tanis, a girl with PWS

28. Angelman Syndrome Cause: Symptoms:
Microdeletion of region q11-13 of chromosome 15 that deletes a gene(s) that is paternally imprinted.
Symptoms:
Normal development until 6-12 months, then delayed development
Disproportionate head growth  microcephaly
Abnormal EEG, seizures
Marked deficit in language (no words to a few words) but better communication using nonvebral methods (e.g., facial expressions)
Motoric problems (balance problems, ataxia of gait, hypermotoric actions)
Attention problems (short attention span)
Emotional exuberance (frequent laughter, smiling)

29. Angelman
Syndrome

30. Angelman Syndrome