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)

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

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

http://www.bbc.co.uk/southyorkshire/myspace/dsa/index.shtml

Erik Nichols and mother, St. Petersburg, FL http://www.sptimes.com/2002/05/12/TampaBay/Lifelong_devotion.shtml

Erik Nichols, 21, and his sister, 17-year-old Lindsey, on their graduation from high school. (Saint Petersburg, FL) http://www.sptimes.com/News/052701/Northoftampa/Sharing_a_triumph_.shtml

James Webster and mother, Anne http://www.dsne.homestead.com/NewParentsInfo.html

Trisomy 21 Karyotype http://www.genecrc.org/site/lc/lc2e.htm

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

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

Turner’s Syndrome Karyotype http://www.genecrc.org/site/lc/lc2e.htm

XYY Karyotype http://www.xyy.nl/XYYMale.gif

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)

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

http://sproutflix.org/all-films/embraceable/ http://decheckgen677s12.weebly.com/ https://williams-syndrome.org/educational-resources/ comments-musical-potential-people-williams-syndrome Ella Grace Larson. From https://williams-syndrome.org/bigred

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

FISH: Williams Syndrome Fluorescent in situ hybridization

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?

Chromosomal Microdeletions: Prader-Willi and Angelman Syndromes

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

http://www. ncbi. nlm. nih. gov/books/bv. fcgi. tool=bookshelf&call=bv http://www.ncbi.nlm.nih.gov/books/bv.fcgi?tool=bookshelf&call=bv.View..ShowSection&searchterm=prader&rid=gnd.section.182

http://www.mgm.ufl.edu/faculty/DDriscoll.htm

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)

Prader Willi Syndrome http://www.bmb.psu.edu/faculty/simpson/lab/07impri/pws.jpg

Tanis, a girl with PWS http://www.bmb.psu.edu/faculty/simpson/lab/07impri/pws.jpg

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)

Angelman Syndrome http://asclepius.com/angel/phopag.html

Angelman Syndrome http://asclepius.com/angel/phopag2.html