Introduction to clinical genetics

Question 1

Features of Down syndrome

Answer 1

trisomy - 3 bodies
round face
protruding tongue
up-slanting palpebral fissures
epicanthic folds - fold on eyelid
developmental delay

Question 2

Di George syndrome

Answer 2

a microdeletion
chunk of chromosome 22 missing
causes cardiac abnormality

Question 3

WBS - Willian Beuren Syndrome features

Answer 3

bright eyes, stellate irides
wide mouth, upturned nose
flattened nasal bridge
heart defects

Question 4

How can you diagnose neurofibromatosis type 1

NF1

Answer 4

A confident diagnosis can be made if two or more of the following symptoms are present:
Six or more café au lait (coffee coloured skin patches) that are larger than 5mm in children, or 15mm in adults
Freckles under the arms or around the groin
Two or more neurofibromas (bumps on or under the skin), or one plexiform neurofibroma (where multiple nerves all come together)
A tumour on the optic nerve, which rarely causes symptoms or affects sight
Bone defecs, such as bowing of the lower leg
Family history of NF1
Two or more tiny brown spots in the iris - Lisch nodules

Question 5

Features of Huntingtons disease

Answer 5

Usually appears in a person’s thirties and forties
Early signs and symptoms can include irritability, depression, small involuntary movement, poor communication or making decisions
Chorea - people with Huntington’s develop involuntary jerking or twitching movements
Decline in thinking and reasoning abilities
Individuals will usually live about 15/20 years after symptoms begin

Question 6

Features of phenylketonuria

Answer 6

Most prevalent inherited defect in amino acid metabolism (phenylalanine)
Untreated phenylketonuria: intellectual disability, behavioural problems
Fair skin and hair : impaired melanin synthesis

Question 7

Familial hypercholesterolaemia

Answer 7

Most common inherited metabolic disease
Disorder of cholesterol metabolism - when you have high cholesterol levels
Leads to premature atherosclerosis, CVD
Disorder is life threatening

Question 8

Tay-Sachs disease (infantile onset form)

Answer 8

Inherited metabolic disorder: deficiency of hexosaminidase A
Leads to accumulation of GM2-ganglioside
Most prevalent Jewish-heritage genetic disease
Prognosis is poor: severe mental and developmental retardation 4-8 months
CNS involvement leads to uncontrollable seizures
Death due to pneumonia or other infections 5-8 years
No available treatment; clinical trials of enzyme replacement therapy
Carrier testing usually by assay of hexosaminidase A activity in plasma or white blood cells

Question 9

47,XX,+21

Answer 9

Trisomy 21/ Down syndrome

Question 10

46,XX,del(5)(p25)

Answer 10

deletion, tip of chr5.

Question 11

Cause of Down syndrome

Answer 11

non-disjunction in meiosis I

Question 12

Edwards syndrome

Answer 12

Trisomy 18
multiple malformations (especially heart, kidneys)
clenched hands with overlapping fingers
Majority of babies die in the first few weeks of life

Question 13

Patau syndrome

Answer 13

Trisomy 13
Multiple malformations - affects midline structures particularly
Incomplete lobation of brain, cleft lip, congenital HD
Majority of babies die in the first few weeks of life

Question 14

Klinefelter syndrome

Answer 14

Abnormality of sex chromosome number
47,XXY
infertility (atrophic testes do not produce sperm)
in some, poorly developed sexual characteristics (pubic and facial hair, deepened voice due to lack of testosterone)
gynaecomastia and osteoporosis
tall

Question 15

Turner syndrome

Answer 15

Abnormality of sex chromosome number
45,X
99% are lost spontaneously in pregnancy
short stature, wide carrying angle of arms
primary amenorrhoea (ovaries involute before birth)
congenital heart disease (coarctation of aorta) 20%