Genetics

Question 1

What is Klinefelter syndrome

Answer 1

one or more extra chromosome - 47 XXY

Question 2

What is the phenotype of klinefelter syndrome

Answer 2

tall stature and long legs
infertility
small testes
gynaecomastia
learning difficulties 

treatment with testosterone to develop secondary sexual characteristics

Question 3

What is patau syndrome

Answer 3

trisomy 13

Question 4

What is the phenotype of patau syndrome

Answer 4

•	Structural defect of brain 
•	Scalp defects 
•	Small eyes, missing eyes and other eye defects
•	Cleft lip and palate
•	Polydactyly
•	Cardiac and renal malformations
macrocephaly
low set ears 

most will die in early childhood

Question 5

What is turners syndrome

Answer 5

45X0 (loss of one X chromosome)

Question 6

What is the phenotype of turners syndrome

Answer 6

•	Lymphoedema of hands and feet in neonates which may persist
•	Spoon shaped nails
•	Short stature – cardinal feature 
•	Neck webbing or thick neck
•	Widely spaced nipples 
•	Congenital heart defects – coarctation of the aorta 
•	Delayed puberty
•	Ovarian dysgenesis resulting in infertility also pregnancy may be possible with IVF
•	Hypothyroidism
•	Renal abnormalities
•	Pigmented moles
•	Recurrent otitis media
•	Normal intellectual function in most
small mandible

Question 7

How would you manage turners syndrome

Answer 7

Start oestrogen aged 11
start progesterone at end of puberty
may need IVF for pregnancy
heart surgery

Question 8

What is Down syndrome

Answer 8

Trisomy 21

can be caused by nondisjunction, translocation, mosaicism

Question 9

What is the down syndrome phenotype

Answer 9

Dysmorphic facial features: 
•	Round face and flat nasal bridge
•	Upslanted palbebral fissures
•	Epicanthic folds 
•	Brushfield spots in iris
•	Small mouth and protruding tongue
•	Small ears
•	Flat occiput and third fontanelle

Other anomalies:
• Short neck
• Single palmar creases, incurved fifth finger and wide sandle gap between toes
• Hypotonia

Question 10

What other conditions are children with down syndrome more prone to

Answer 10

• Congenital heart defects (40%)
• Duodenal atresia
• Hirschsprung disease

Later medical problems:
• Delayed motor milestones
• Moderate to severe learning difficulties
• Small stature
• Increased susceptibility to infections
• Hearing impairment from secretory otitis media
• Visual impairment from cataracts, squints and myopia
• Increased risk of leukaemia and solid tumours
• Risk of atlanto-axial instability
• Increased risk of hypothyroidism and coeliac disease
• Epilepsy
• Alzheimers disease

Question 11

What is Edwards syndrome

Answer 11

trisomy 18

Question 12

What is the phenotype edwards syndrome

Answer 12

Microcephaly
prominant occiput
ocular abnormalities
short sternum
small mouth, jaw (micrognanthia) and neck
‘Rocker-bottom’ feet (flexed big toe and prominant heels) and flexed, overlapped fingers
cardiac and renal malformations

Question 13

What is fragile X syndrome

Answer 13

X linked recessive disorder.

A trinucleotide repeat disorder. Expansion of triplet repeat CGG in FRAXA gene FMR1

Question 14

What is the phenotype of fragile X syndrome

Answer 14

Facial:
broad forehead
elongated face
large prominent ears
strabismus
highly arched palate

Other features:
•	Learning difficulty (IQ 20-80) mean 50
•	Autistic features
•	Hyperactivity 
•	Macro-orchidism (abnormally large testes) 
•	Mitral valve prolapse
•	Joint laxity

Question 15

What is Duchenne muscular dystrophy

Answer 15

an X-linked inherited disorder caused by a deletion on the short arm of the X chromosome (at the Xp21 site). This site codes for a protein called dystrophin

Question 16

What is the phenotype of duchenne muscular dystrophy

Answer 16

floppy baby
waddling gait
language delay
Gowers sign
The progressive
muscle atrophy and weakness means that they are no
longer ambulant by the age of about 10–14 years. Life
expectancy is reduced to the late twenties from respiratory
failure or the associated cardiomyopathy. About
one-third of affected children have learning difficulties.
Scoliosis is a common complication.

Question 17

Management of duchenne muscular dystrophy

Answer 17

orthoses
physiotherapy
steroids

Question 18

What is angelmans syndrome

Answer 18

• Caused by a deletion in the Maternally inherited chromosome 15 or paternal uniparental disomy

Question 19

What is the phenotype of angelmans syndrome

Answer 19

• “Happy puppet” unprovoked laughing/clapping
• Microcephaly
• Mental retardation
• Seizures
• Ataxia
• Broad based gait

Question 20

What is prader willi syndrome

Answer 20

• Caused by a deletion in the paternally inherited chromosome 15 or maternal uniparental disomy

Question 21

What is the phenotype of prader willi syndrome

Answer 21

• Neonatal hypotonia and poor feeding
• Failure to thrive in infancy
• Hypogonadism
• Developmental delay
• Moderate Mental Retardation
• Hyperphagia and obesity
• Small genitalia

Question 22

What is noonan syndrome

Answer 22

Autosomal dominant disorder

Question 23

What is the phenotype of Noonan syndrome

Answer 23

• Occasional mild learning difficulties
• Short webbed neck with trident hair line
curly/wooly hair
• Pectus excavatum
• Short stature
• Congenital heart disease – especially pulmonary stenosis and atrial septal defects

Question 24

What is williams syndrome

Answer 24

Microdeletion of the elastin gene

Question 25

What is the phenotype of williams syndrome

Answer 25

•	Short stature
•	Transient neonatal hypercalcaemia
•	Congenital heart disease (supravalvular aortic stenosis)
•	Mild to moderate learning difficulties
Sunken nasal bridge
puffiness around the eyes
epicanthal fold
blue eyes starry pattern
long upper lip length
small and widely spaced teeth
wide mouth
prominent lower lip
small chin