Chromosomal conditions

Question 1

Downs

Answer 1

Trisomy 21

Downs syndrome
extra-copy of chromosome

Clinical features

• brachyepahly (flat heat)
• single palmar crease
• brushfield spots on iris
• moderal metal retardation
• protruding tongue

More common as maternal age increases
-1/25 >45 years

Question 2

Edwards syndrome

Answer 2

Trisomy 18

Clinical features

• small chin
• clenched hands with overlapping fingers
• malformations of heart, kidney and other organs

Only 10% survive 1st year

Question 3

Pataus syndrome

Answer 3

Trisomy 13

Clinical features

• microcephaly
• cleft lip and palate
• polydactyly (post-axial)
• CNS abnormalities
• micropthalmia

50% die within one month

Post axial- litter finger side - extra digit
Pre-axial - thumb side - extra digit

Question 4

Fragile X syndrome

Answer 4

X-linked recessive

Genetic anticipation

• 5 UTR of FMR1 gene
• most common inherited cause f learning difficulties

DS not inherited!!

Question 5

Pateua, edwards and downs arise from

Answer 5

maternal non-disjunction (failure of separation 21, 18, 13)

Question 6

Assessment and screening

Answer 6

Assess clinical history (age of onset, progression), family history (consanguinity, still birth, misccarriages) & dysmorphic features

Question 7

Dysmorphic features

Answer 7

Head shape: macro& microcephaly

Eyes- palpebral fissures (size and slants) , spacing (hypertelorism)

Ears- size, shape, position, rotation

Nose- size, nares

Philtrum: smooth, fetal alcohol syndrome

Limb: length

Skin: lumps, pigmentation

Hands and feet: palmar creases, polydactyly and syndactyly

Question 8

Pre-implanation diagnosis

Answer 8

Remove 1/2 clls for testing 3 days after fertilisation (embryogenesis).

Then tested by PCR - 1/2 unaffected cell are implanted back into mother

Question 9

GMC guidlines

Answer 9

1. pre-symptomatic testing should only be carried out after full discussion, provision of info and suppot + informed consent
2. Genetic testing of an untreatable adult - onset disorder should be post-poined until child can give full consent
3. Patient confidentialy is crucial nevertheless GMC guidlelines uggest that in exception circumstance, where there is risk of serious harm to others from non-disclosure. Docot makes dicision

Question 10

Genetic screening tests

Answer 10

Screening tests are offered to a whole population where each person has a low individual risk

Must be:

• cheap
• non invasive
• offered at three stages of life
• clearly defined disorder

Question 11

Specificty (false positives)

Answer 11

TN/ (FP+ TN)

Question 12

Sensitivity (false negative)

Answer 12

TD/ (TP+ FN)