Genetics Flashcards
What is Peutz Jeghers syndrome?
Autosomal dominant benign hamartomatous polyps in GI tract and hyperpigmented macules on the lips and oral mucosa (melanosis)
Name 3 most common autosomal dominant conditions
familial hypercholesterolaemia, polycystic kidney disease, Huntington’s Disease, thrombophilias
Name 4 chromosomal disorders
Down syndrome, trisomy 18, Turner syndrome, Klinefelter syndrome
Name 3 most common autosomal recessive conditions
cystic fibrosis, hereditary haemochromatosis, haemoglobinopathies
Name 3 x-linked disorders
Fragile X Syndrome
Duchenne and Becker Muscular Dystrophy, haemophilia
Trisomy screening
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
Trisomy 21 abnormalities
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
Features suggesting genetic condition
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.
CF symptoms
Autosomal recessive
Persistent productive cough
Chronic sinusitis
Pancreatic insufficiency
Failure to thrive
Male infertility
Features of trisomy 18
Edward’s syndrome
often results in stillbirth or death in infancy.
small jaw, prominent occiput, overlapping fingers and rocker bottom feet
Features of Turners syndrome
Female with one X chromosome
Short stature
Webbed neck
Widely spaced nipples
Coarctation aorta
Horseshoe kidney
Failure puberty/menarche
Features of Klinefleter syndrome
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
Features of Becker muscular dystrophy
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
Features Duchenne muscular dystrophy
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
Onset of polycystic kidney disease
Autosomal dominant PKD age 30-50
Autosomal recessive PKD onset childhood
Features of haemochromatosis
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,
Treatment of haemochromatosis
Venesection
Reduce iron intake in diet
Features of Huntington’s
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
What diseases does the newborn heel prick blood spot test for?
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)
When someone is diagnosed with breast cancer, what features would make a genetics referral required?
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)
What are the criteria for referral for genetics with breast cancer?
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
Management of people with incr risk breast/ovarian cancer
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)
Name 3 genetic mutation that incr risk breast cancer
BRCA1, BRCA2 or TP53
Features of Marfan’s
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
Management of Marfan’s
Refer genetics/echo
Advise immediate medical attention if chest pain (risk of aortic rupture)
avoid contact sports
B-blocker + ARB
What is APC?
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
What is HNPCC?
hereditary non-polyposis colon cancer
Associations- ovarian, prostate, stomach cancers
Screening- Colonoscopy, endoscopy, cystoscopy and pelvic screening
