Clinical Aspects Flashcards
What IQ for LD, mild, moderate, severe?
<70= LD. Mild= 50-70
Moderate 35-50
Severe 20-40
Profound <20
What is the functional definition for LD?
Dysfunction or impairment in >2 areas of communication, work, self care or social skills
% of unknown causes for LD (mild and severe)
80% for mild
30-50% severe
What 3 areas is dysmorphology concerned with?
1) deformation eg. Excessive moulding
2) disruption eg breakdown of normal development
3) malformation- eg isolated cleft lip and/or palate
Words for
1) shortening of proximal limbs
2) shortening of distal limbs
3) shortening of digits
1) rhizomelic
2) mesomelic
3) acromelic
What does syndactyly mean?
Joined together
What does USPF and DSPF mean ?
Upslanting palpebral fissures (corner of ur eyes)
Downslanting palpebral fissures
Indications for chromosome analysis
1) developmental delay
2) IUGR/ failure to thrive
3) microcephalic
4) facial dysmorphism
5) multiple congenital malformations
2 or more required
6% of unexplained mr is due to what?
Cryptic telomeric rearrangement - can test with multi probe fish
How many fragile sites in humans? What are they sensitive to?
>
- Sensitive to folate
Where is FRAXA and FRAXE?
FRAXA = Xq27.3 FRAXE = Xq28
What is the Sherman paradox?
Risk of developing mr is dependent on the individuals position in the pedigree with risk increasing in later generations
Characteristics of Fragile x: occurrence, when does classic features evolve, facial features, behaviour.
1 in 5,500 boys
Evolves at puberty
Long face, prominent ears, large nose
IQ 40, hyperactivity, impulsiveness, hand flapping
What causes fragile x?
cGG trinucleotide repeat in 5’UTR of FMR1 within non coding exon 1.
What is FXTAS? What are symptoms?
Fragile x associated tremor and ataxia syndrome.
Late onset progressive cerebellum ataxia and intention tremor in makes with permutations.
Peripheral neuropathy, short term memory loss, muscle weakness and autonomic dysfunction
Occurrence in f FXTAS in males and females?
40-45% of males
8-16.5% of females
What size permutations are at risk of expansion to full mutation?
52-70 repeats - no chance
80-89 76% risk
100+ 100% risk
What causes FRAXE and when is it tested for?
GCC expansion in FMR2 on Xq28
Tested if family history of x linked mental retardation
What % of patients with LD have a cytogenetic abnormality?
16%
After downs, patau and Edwards what are th most common autosomal trisomies (mosaic)
8 and 9
True or false: no autosomal monosomy is viable at term
True
What trisomy is the most common cause of spontaneous miscarriage?
Trisomy 16
What is the most common cause of DS?
Non dysjunction event at maternal meiosis 1st division 94%
Second most common cause f DS?
Unbalanced robertsonian translocation =4%
What causes mosaic DS? (2%)
Post zygotic, mitotic non disjunction event
Can also occur as a corrective event - aka trisomy rescue
Percentages of DS caused by non-disjunction in mat I, mat II, Pat I, Pat II?
Mat I = 68%
22%
5%
5%
Features of patau
Microcephaly
Polydactyly
Holoprosencephaly- cleft palate nose and he anomalies
Features of Edwards
Microcephaly
Heart problems
Clenched hands and rocker bottom feet
Features of mosaic trisomy 8
Mild to moderate MR
Deep plantar furrows - palms and soles of feet
Features of mosaic trisomy 9
MR
Congenital heart disease
Downturned corners of the mouth
What are ESACs?
Extra small additional chromosomes also called markers
Often mosaic
How to investigate esacs?
C- banding to see if contains heterochromatin or euchromatin
Silver staining to see if contains Acrocentric non coding material
Genetic cause of pallister killian syndrome?
Mosaicism for an additional isochromosome made up of two 12 p. (Tetrasomy 12p)
How to test for pallister killian
Rarely seen in metaphase from blood but can be through FIsh of skin tissue r sometimes blood
Features of pallister killian - physical and behavioural
Hypopigmented hyperpigmented skin
Mr, hypotonia and epilepsy
High forehead, sparse hair, epicanthal folds
What is the cause of cat eye syndrome
Mosaicism Small isochromosome- 2 copies of proximal part of 22q
Often tissue specific
Besides PKS and cat eye name two other mosaic esacs
I(15)(q11)
I(5)(p10)
