What is ? Angelman Syndrome Angelman syndrome is a genetic disorder that causes developmental delay and neurological problems. The physician Harry Angelman first delineated the syndrome .in 1965
? What is Prader willi Syndrome PWS is a complex genetic disorder that includes short stature, mental retardation or learning disabilities, incomplete sexual development, characteristic behavior problems, low muscle tone, and an involuntary urge to eat constantly, which, coupled with a reduced need for calories, leads to .obesity In 1887, Langdon-Down described the first patient with PWS described in 1956 by Andrea Prader whoreported a .series of patients with similar phenotypes
PWS : Cause PWS results from the loss of the paternal copy .of chromosome 15 q11.2-13 Most cases of PWS arise sporadically. More than 70% of patients have a deletion of the paternal copy; approximately 25% of patients with PWS have maternal uniparental disomy for chromosome 15. The remainder of patients with this disorder have a translocation or other . structural alteration in chromosome 15
AS Cause Anglman Syndrome is caused by an abnormality on chromosome 15 which occurs around the time of conception. The majority of cases (about 70%) are caused by a deletion on the chromosome 15 inherited from the , mother
AS can be caused by a large deletion of the region of the maternal chromosome 15 that contains UBE3A,or by a DNA sequence change (mutation) in the UBE3A gene inherited from the mother UBE3A This gene encodes a protein called a ubiquitin protein ligase, and UBE3A is believed to . be the causative gene in AS
AS can also be caused by inheritance of 2 normal copies of UBE3A from the father with no copy inherited from the .mother
Another cause of AS, referred to as imprinting defect, occurs when the chromosome 15 inherited from the mother has the paternal pattern of gene functioning and DNA .methylation
Angelman Syndrome Symptoms Developmental delay, functionally severe-1 Speech impairment, none or minimal use of-2 ;words receptive and non-verbal communication-3 skills higher than verbal ones seizures-4 Movement or balance disorder, usually ataxia-5 of gait and/or tremulous movement of limbs Behavioral uniqueness: any combination of-6 frequent laughter/smiling; apparent happy demeanor;-7 easily excitable personality, often with hand flapping movements; hypermotoric behavior; short attention span
?Why it is called happy Puppet Because of laughter and happiness . The laughter in AS seems mostly to be an expressive motor event; most reactions to stimuli, physical or mental, are accompanied by laughter or laughter-like facial grimacing. Although AS children experience a variety of .emotions, apparent happiness predominates
-1Fluorescent in situ hybridization FISH is the preferred method of identifying the deletion since it is typically not detected by routine chromosome study. Alternatively, comparative genomic hybridization (CGH) .can be used to detect the deletion Uniparental disomy (UPD) study-2 In approximately 7% of individuals, . uniparental disomy (UPD) is detected using DNA polymorphism testing-3 .Targeted mutation analysis Sequence analysis-4
AS has been reported throughout the world among divergent racial groups. In North America, the great majority of known cases seem to be of Caucasian origin. Although the exact incidence of AS is unknown, an estimate of between 1 in 15,000 to 1 in `30,000 seems reasonable
The incidence of PWS is between 1 in 12,000 and 1 in 15,000 live births
AS
PWS
• اعداد الطالب : باسل الخياط Group 4