Cytogenetics And Learning Disorders Part 2

Question 1

Provide some details on cri-du-chat syndrome

Answer 1

• terminal del5p
• cat-like/high pitched cry
• microcephaly, poor muscle tone and mental retardation

Question 2

Provide some details on wolf hirschhorn syndrome

Answer 2

• terminal del4p
• prominent forehead, wide set eyes and broad beaked nose
• collectively described as ‘Greek warrior helmet’ features
• severe mental retardation

Question 3

Provide some details on Miller dieker syndrome

Answer 3

• terminal del17p
• lissencephaly: smooth brain with lack of gyri due to incomplete neuronal migration
• severe mental retardation, seizures, reduced life expectancy

Question 4

Provide some details on smith magenis syndrome

Answer 4

• interstitial deletion of proximal 17p (p11.2)
• common deletion region = 4Mb
• mental retardation, behaviourial problems, self harming and sleep disturbance

Question 5

Explain non-allelic homologous recombination (NAHR) in the context of recurrent Microdeletions and microduplications

Answer 5

NAHR events occur between regions of homology interspersed throughout the genome. These are polymorphic regions of low copy repeats (LCRs).

The presence of two LCRs within close proximity predisposes to NAHR resulting in either deletion or duplication of the intervening sequence

Question 6

Provide details on digeorge syndrome

Answer 6

• Deletion at 22q11.2
• variable phenotype that includes aortic arch defects, learning difficulties, hypoglycaemia
• almond shaped eyes, long fingers and toes
• may be inherited from phenotypically normal parent
• carrier has 50% risk of passing the deletion on

Question 7

Provide details on Williams-Beuren syndrome

Answer 7

• deletion at 7q11.23
• clinical features include heart defects, elfin features, ‘cocktail party manner’, learning difficulties, stellate iris pattern

Question 8

What are the two main types of loss of genetic material? Give examples

Answer 8

1. Deletion syndromes: Cri-du-chat, wolf hirschhorn, miller dieker, smith magenis
2. Microdeletion syndromes: DiGeorge (Velocardiofacial syndrome), williams-beuren syndrome. Reciprocal duplications for these regions also exist