Genetics

Question 1

What is Peutz Jeghers syndrome?

Answer 1

Autosomal dominant benign hamartomatous polyps in GI tract and hyperpigmented macules on the lips and oral mucosa (melanosis)

Question 2

Name 3 most common autosomal dominant conditions

Answer 2

familial hypercholesterolaemia, polycystic kidney disease, Huntington’s Disease, thrombophilias

Question 3

Name 4 chromosomal disorders

Answer 3

Down syndrome, trisomy 18, Turner syndrome, Klinefelter syndrome

Question 4

Name 3 most common autosomal recessive conditions

Answer 4

cystic fibrosis, hereditary haemochromatosis, haemoglobinopathies

Question 5

Name 3 x-linked disorders

Answer 5

Fragile X Syndrome
Duchenne and Becker Muscular Dystrophy, haemophilia

Question 6

Trisomy screening

Answer 6

Combined test, uses maternal age, nuchal translucency measurement and blood tests (hCG and PAPP-A) and is performed at 10 to 14 weeks of pregnancy

Question 7

Trisomy 21 abnormalities

Answer 7

flattened nose;
upslanting eyes;
epicanthic folds
AVSD, VSD, ASD, ToF, PDA
cataracts;
strabismus;
myopia;
Hearing problems
single palmar creases; and wide gap 1st +2nd toe
Hirschsprung’satresia/stenosis
coeliac disease.
learning difficulties;
hypotonia;
seizures
early-onset Alzheimer’s
hypothyroidism
short stature;
delayed puberty;
decreased virilisation in male
Frequent infections

Question 8

Features suggesting genetic condition

Answer 8

Cancer affecting younger than usual or multiple family members
Familial hypercholesterolaemia.
Sudden cardiac deaths-long QT, syndrome/HOCM
3+miscarriages or stillbirths.
Multiple congenital anomalies, dysmorphic features, growth and developmental delay.
Ashkenazi Jewish ancestry.

Question 9

CF symptoms

Answer 9

Autosomal recessive
Persistent productive cough
Chronic sinusitis
Pancreatic insufficiency
Failure to thrive
Male infertility

Question 10

Features of trisomy 18

Answer 10

Edward’s syndrome
often results in stillbirth or death in infancy.
small jaw, prominent occiput, overlapping fingers and rocker bottom feet

Question 11

Features of Turners syndrome

Answer 11

Female with one X chromosome
Short stature
Webbed neck
Widely spaced nipples
Coarctation aorta
Horseshoe kidney
Failure puberty/menarche

Question 12

Features of Klinefleter syndrome

Answer 12

Men with XXY
hypermobile weak joints, delayed gross motor development, shyness, dyslexia/dyspraxia, taller than expected, broad hips, poor muscle tone, delayed facial hair, gynaecomastia, infertility, low sex drive, small testes, and erectile dysfunction
Inc risk T2DM, clots, lupus, breast cancer

Question 13

Features of Becker muscular dystrophy

Answer 13

X-linked
Mean onset age 11
difficulty walking, running, hopping, jumping;
difficulty climbing stairs;
exercise intolerance;
frequent falls;
anomalous gait
Raised CK
Dilated cardiomyopathy/arrythmia

Question 14

Features Duchenne muscular dystrophy

Answer 14

X-linked
Mean onset age 3
developmental delay/ loss of motor milestones;
toe-walking;
clumsiness;
frequent falls; and
positive Gower’s sign
Pseudohypertrophy calf muscles
Raised CK
Dilated cardiomyopathy/arrythmia

Question 15

Onset of polycystic kidney disease

Answer 15

Autosomal dominant PKD age 30-50
Autosomal recessive PKD onset childhood

Question 16

Features of haemochromatosis

Answer 16

Autosomal recessive, HFE gene
Early features: weakness and lethargy;
abdominal pain;
arthralgia MCPJs;
weight loss;
asymptomatic hepatomegaly

Later features:
skin bronzing;
diabetes mellitus;
cardiomyopathy;
hypogonadism, impotence, infertility or premature menopause,
hepatomegaly;
cirrhosis
HCC + cholangiocarcinoma,

Question 17

Treatment of haemochromatosis

Answer 17

Venesection
Reduce iron intake in diet

Question 18

Features of Huntington’s

Answer 18

Autosomal dominant
progressive neurodegenerative Early: chorea, clumsiness, agitation, delusions, disinhibition, apathy, hallucinations
Middle: dystonia, chorea, weight loss, speech and swallowing difficulties, ataxia, slow voluntary movements, progressive cognitive decline.
Late: dementia, rigidity, bradykinesia, inability to walk, inability to speak
Mean age death age 55

Question 19

What diseases does the newborn heel prick blood spot test for?

Answer 19

CF
Sickle cell
Congenital hypothyroidism
PKU
MCADD
maple syrup urine disease
isovaleric acidaemia
glutaric aciduria type 1
homocystinuria

In some areas: SCID (severe combined immunodeficiency)

Question 20

When someone is diagnosed with breast cancer, what features would make a genetics referral required?

Answer 20

bilateral breast cancer
male breast cancer
ovarian cancer
Jewish ancestry
sarcoma in relative<45
glioma or childhood adrenal cortical carcinomas
complicated patterns of multiple cancers at a young age
paternal history of breast cancer (2+ relatives)

Question 21

What are the criteria for referral for genetics with breast cancer?

Answer 21

1 1st degree female relative breast cancer age<40

1 1st-degree male relative breast cancer any age

1 1st-degree relative with bilateral breast cancer, 1st primary age< 50 years

2 1st-degree relatives, or 1 1st-degree and 1 2nd-degree relative, breast cancer any age

1 1st-degree or 2nd-degree relative breast cancer any age + 1 1st-degree or 2nd-degree relative ovarian cancer at any age (1 of these should be a first-degree relative)

3 1st-degree or 2nd-degree relatives breast cancer any age

Question 22

Management of people with incr risk breast/ovarian cancer

Answer 22

Surveillance (MRI/USS/Mammography)
Risk reduction (avoid hormonal medication, smoking, obesity, alcohol)
In BRCA1 COCP reduced risk ovarian cancer but incr risk breast cancer
Oophorectomy age 40/mastectomy
Chemoprevention 5yrs (tamoxifen pre-menopause, anastrozole post menopause)

Question 23

Name 3 genetic mutation that incr risk breast cancer

Answer 23

BRCA1, BRCA2 or TP53

Question 24

Features of Marfan’s

Answer 24

Autosomal dominant
Multisystem disorder of connective tissue
Suspect if +ve FHx or
is tall with long fingers and at least one of: pigeon chest, joint hypermobility, lens problem, previous pneumothorax, heart murmur(MR).

Other features: myopia, risk of retinal detachment, glaucoma, and early cataracts, scoliosis, aortic dissection

Question 25

Management of Marfan’s

Answer 25

Refer genetics/echo
Advise immediate medical attention if chest pain (risk of aortic rupture)
avoid contact sports
B-blocker + ARB

Question 26

What is APC?

Answer 26

Familial adenomatous polyposis (FAP) occurs when adenometous polyposis coli (APC) tumour suppressor gene is mutated.
Autosomal dominant
profound lifetime risk for colorectal cancer, prophylactic colectomy age 16-25
Colonoscopies from age 12, gastroscopies from age 25

Question 27

What is HNPCC?

Answer 27

hereditary non-polyposis colon cancer
Associations- ovarian, prostate, stomach cancers
Screening- Colonoscopy, endoscopy, cystoscopy and pelvic screening