Paeds - Genetics

Question 1

Downs syndrome aetiology

Answer 1

Trisomy 21

Non-dysjunction - 94%

• Pair of chromosomes fail to separate
• Increased risk with maternal age
• No need to analyse parental chromosomes

Translocation - Robertsonian

• 21 to 14
• Parents need to be tested

Mosaicism - Non-dysjunction in normal cells
- Leads to milder phenotypes

Question 2

Downs syndrome risk

Answer 2

Related to maternal age

20 - 1 in 1500
30 - 1 in 800 
35 - 1 in 270 
40 - 1 in 100 
45 - 1 in 50

Question 3

Downs syndrome facial features

Answer 3

Epicanthic folds 
Brushfield spots 
Flat nasal bridge 
Small mouth - Pseudomacroglossia 
Flat occiput 
Small ears 
Up-slanting palpebral fissures

Question 4

Downs syndrome systemic features

Answer 4

Hands and feet

• Single palmar crease
• Sandal gap

Cardiac - ASD, VSD, ToF

GI

• Hischsprung’s
• Duodenal atresia
• GORD
• Coeliac

Neuro

• Seizures
• Motor delay
• Hearing impairment
• Cataract
• Squint

Question 5

Downs syndrome associated conditions

Answer 5

SHELAC - T

Subfertility 
Hypothyroid 
Epilepsy 
Leukaemia 
Alzheimer's 
Coeliac 

Type 1 DM

Question 6

Downs syndrome screening

Answer 6

11-13+6 weeks - Combined

• Increased nuchal thickness
• Increased serum HcG
• Decreased PAPP-A

15-20 weeks - Quadruple test

• Increased serum HcG
• Decreased AFP
• Decreased oestradiol
• Increased inhibin A

Question 7

Downs syndrome diagnostic tests

Answer 7

Amnioscentesis - 15 weeks
Chorionic villous sampling - 11-14 weeks

Non-invasive pre-natal diagnosis - 10 weeks - Foetal DNA

Question 8

Downs syndrome management

Answer 8

MDT
Counselling

Screening - SHELAC-T

• Subfertility
• Hypothyroidism
• Epilepsy
• Leukaemia
• Alzheimer’s
• Coeliac
• Type 1 DM

Question 9

Turner’s syndrome

Answer 9

45X - Short ugly girls with fat feet

Shield chest 
Short stature 
Webbed neck 
Spoon nails 
Lymphoedema of hands and feet 
Pigmented moles 
High arched palate

Ovarian dysgenesis
Primary amenorrhoea

Cardiac abnormalities - CoA and aortic valve
Renal abnormalities

Question 10

Klinefelters syndrome

Answer 10

XXY - Tall feminine boys with big boobs

Tall stature

Hypogonadism 
Gynaecomastia 
Delayed puberty 
Subfertility 
Raised gonadotropin

Question 11

Patau’s syndrome

Answer 11

Trisomy 13 - PPPPPP

Holoprosencephaly
Cleft palate
Micro-ophthalmia

Polydactly

Cardiac abnormalities
Renal abnormalities

Question 12

Edward’s syndrome

Answer 12

Trisomy 18 - EF - Feet and fingers

Syndactly
Flexed overlapping fingers
Rocker bottom feet

Low ears
Small eyes and mouth

Prominent occiput
Structural brain defects

Cardiac abnormalities
Renal abnormalities

Question 13

Prader Willi syndrome

Answer 13

PATERNAL DELETION
Fat floppy baby

Hypotonia
Hyperphagia
Obesity

Short
Behavioural problems
Hypogonadism

Question 14

Angelman’s syndrome

Answer 14

MATERNAL DELETION

Happy clapper
Angelman’s - Almond face

Ataxia
Broad based gait
Seizures
Hyperactive

Question 15

William’s syndrome

Answer 15

Microdeletion - Mingram
Chromsome 7

Short
Friendly
Elfin like face

Transient neonatal hypercalcaemia
Supravalvular aortic stenosis

Learning difficulties

Question 16

Fragile X syndrome

Answer 16

Trinucleotide repeat - CGG

Fragile X - Facial - Forehead

Macrocephaly
Facial
- Prominent mandible
- Broad forehead

Macro-orchidism
Scoliosis

Hypotonia
Mitral valve prolapse

Learning difficulties
Autism

Question 17

Noonan syndrome

Answer 17

Autosomal dominant - Similar to Turner’s

Webbed neck
Short stature
Pectus excavatum

Cardiac

• Pulmonary stenosis
• ASD