Presented By: Stephanie Asselstine & Jessica Williams

What is WS? Genetically based. Caused by a deletion in chromosome 7. Affects mental and physical development.

Phenotypic Symptoms Distinct Facial Features Short in stature Cardiovascular problems Blood vessel problems Kidney problems Developmental problems Slight mental retardation Behavioral problems similar to attention deficit disorder Social butterflies Excessive calcium levels (Hypocalcaemia) Hypersensitivity to sound Slow weight gain Underweight infants Colicky infants  WIDE ARRAY OF SYMPTOMS CAUSED BY A DELETION

The Deletion A De-Novo deletion Deletion occurs at the 7q11.23 portion of chromosome 7 (the long arm of the chromosome at position 11.23). Deletion is random. If the deletion covers the whole portion, approximately 25 genes will be cut out of the genome. The random deletion is the reason why individuals show such a wide range of symptoms. Why does the deletion occur? The 7q11.23 region where the deletion occurs, contains about 25 genes. Chromosome 7

Pattern Of Inheritance Williams syndrome is an Autosomal Dominant condition. Normal parents will NEVER pass the deletion to their children. There is a 50% chance of an effected parent passing WS to their children. Deletion Sister Chromatids pair at metaphase plate Chromatids separate and cell starts to cleave. 2 new cells are formed. One with the deletion, one without.

Demographics Extremely uncommon 1 in every 7,500 – 20,000 births are effected Classified as a “rare disease”.

Diagnosis There are a number of ways to diagnose WS. 1) Physical Examination by doctor. 2) Special blood test called FISH (fluorescent in situ hybridization) test. 3) Prenatal testing. Positive Williams Syndrome FISH assay. (Chromosome 7) The elastin gene is found on only one chromosome. The other copy carries an elastin gene deletion.

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GENES LOCATED IN DELETED REGION ELN CLIP 2 LIMK1 GTF2I GTF2IRD1 NCF1

ELN NORMAL GENE FUNCTION RESULTING SYMPTOMS Protein elastin Strength & flexibility of organs and tissues Missing 1 copy of ELN Reducing elastin production by ½ Restriction of blood flow Cardiovascular disease Joint problems & loose skin

CLIP2 NORMAL GENE FUNCTION RESULTING SYMPTOMS Protein CLIP 115 Found in the Brain Structure & Function of Nerve Cells Cytoskeleton Missing 1 copy of CLIP2 Unique behavioural traits Disrupts normal regulation of cytoskeleton

LIMK1 NORMAL GENE FUNCTION RESULTING SYMPTOMS Found in Brain Nerve cells: visual-spatial information Cytoskeleton Missing 1 copy of LIMK1 Writing & reading Development & function of nerve cells

GTF2IRD1 NORMAL GENE FUNCTION RESULTING SYMPTOMS Transcription factor Turns genes on/off Active in body tissues Skeletal muscles Craniofacial development Missing 1 copy of GTF2IRD1 Characteristic features

GTF2I NORMAL GENE FUNCTION RESULTING SYMPTOMS Proteins BAP-135 and TFII-I Bap-135: immune system function Active in B cells TFII-I: active in brain Transcription factor Missing 1 copy of GTF2I Intellectual disability Dental abnormalities Difficulties reading & writing

NCF1 NORMAL GENE FUNCTION RESULTING SYMPTOMS Protein neutrophil cytosolic factor 1 Immune system Missing 1 copy of NCF1 Lowers risk of high blood pressure

Treatment Many specialist and doctors visits Physical therapy Psychological counseling Speech and occupational therapy Music therapy