genetics Flashcards
do people who are low risk of hereditary cancer get additional screening
no - same risk as general public
how can people with BRAC1/2 genes lower their risk of breast cancer
prophylactic mastectomy
what are the main features of NF2
acoustic neuromas (usually bilateral)
CNS and spinal tumours
A few Café Au lait spots
what cancers are associated with HNPCC/ lynch
colorectal endometrial urinary tract ovarian gastric
ethically when should children or adolescents be genetically tested
if there are potential medical benefits
what is the biggest environmental trigger for disease
alcohol consumptions
how often should people with high risk HNPCC get a colonoscopy
2 yearly form 25
what is the management of suspect NF1 in a newborn
Annual review of affected individuals and at risk children until diagnosis can be excluded (5 years) or genetic test clarified
- Blood pressure -Spine for scolisosis
- Tibia for unusual angulation
- Visual acuity and visual fields
- Educational assessment - patient report unusual symptoms
why may adults be referred to genetics
Diagnosis understand why symptoms have occurred
Predictive testing – if at risk
Carrier testing or cascade screening – find risk to children
Family history (including cancer) – give opportunity of prevention
Fetal loss or recurrent miscarriages.
what is the appropriate follow up for people you suspect to have a hereditary cancer syndrome
curate risk assessment
effective genetic counselling
appropriate medical follow up
what is the diagnostic criteria for NF1
café au lait spots - 6 or more/big >1/2cm - neurofibromas - 2 or more
axillary freckling Lisch nodules (specks in iris, asymptomatic)
optic glioma (optic chiasm) - thinning of long bone cortex (false joint)
family history
(need +2)
which people may yo suspect a hereditary cancer syndrome in
¥ Cancer in 2 or more close relatives (on same side of family)
¥ Early age at diagnosis
¥ Multiple primary tumors
¥ Bilateral or multiple rare cancers
¥ Characteristic pattern of tumours (e.g. breast and ovary, endometrium and bowel)
¥ Evidence of autosomal dominant transmission
how is duchenne muscular dystrophy inherited
x linked
what kind of genes are mutated in HNPCC/ lynch
mismatch repair genes
describe the multistep carcinogenesis of colon cancer
normal epithelium LOSS OF APC hyper proliferative epithelium early adenoma ACTIVATION OF K-RAS intermediate adenoma LOSS OF 18Q late adenoma LOSS OF TP53 carcinoma OTHER ALTERATIONS metastasis
what chromosome is affected in NF2
chromosome 22
what are benefits of genetic testing
- Identifies highest risk
- Identifies non-carriers in families with a known mutation
- Allows early detection and prevention strategies
May relieve anxiety
what are some features of myotonic dystrophy
Bilateral late-onset cataract
Muscle weakness, stiffness & myotonia (characteristic)
Low motivation
facial weakness
bowel problems (IBS/ constipation
diabetes mellitus more common
Heart block – monitor as cause of unexpected death, treat with pacemaker
Death post-anaesthetic a risk if not monitored – respiratory compromise due to muscle weakness, monitor for much longer after surgery
are somatic mutations heritable
no
how often should people with moderate risk HNPCC get a colonoscopy
35 and 55
what are risks and limitations of genetic testing
- Does not detect all mutations
- Continued risk of sporadic cancer
- Efficacy of interventions variable
May result in psychosocial or economic harm
what makes myotonic dystrophy worse in each generation
anticipation (increasing repeats)
how many pairs of chromosomes are in the human genome
23
~25,000
how do tumours divide
uncontrollably
what age do people with lynch syndrome typically present
45 years
what sex is affected by X linked conditions
males
do AD mutations have skipped generations
no
do people who are medium risk of hereditary cancer get additional screening
yes - increased frequency
what gene is affected in Neurofibromatosis type 1
17q - tumour supressor gene
list some possible chromosomal models of inheritance
translocations
deletions/ micro deletion
numerical
what is the lifetime risk of breast cancer if you have the BRAC1/2 gene
60-80%
what mutation is seen in myotonic dystrophy
CTG repeat in chromosome 19, exhibits anticipation (increasing repeats) with increasing severity in each generation
what cancers are increased in males who have the BRAC2 gene
prostate
breast
name 3 diseases that have a genetic aetiology with germ line variations present in every cell (AD)
NF1
myotonic dystrophy
tuberous sclerosis
what genes cause tuberous sclerosis
TSC 1
TSC 2
do people who are high risk of hereditary cancer get additional screening
yes + gene testing
what are clinical features of tuberous sclerosis
learning difficulty
seizures
skin lesions - depigmented macules, angiofibromas (butterfly rash, raised areas, face/ around mouth), fibrous plaque forehead, shagreen patches, subungual fibromas (toenail groove, diagnostic aid)
Kidney - cysts and angiomyolipomata (can predispose to renal malignancy)
Phakomas in eye - benign unless on macula
Rhabdomyomas in heart – tumour of heart muscle
what is the lifetime risk of ovarian cancer if you have the BRAC1/2 gene
20-50%
BRAC1> BRAC2
what is the difference between a total (Simple) mastectomy and subcutaneous mastectomy
subcutaneous is nipple preserving
what are some minor features of neurofibromatosis type 1
Macrocephaly (big head) Short stature
Dysmorphic facial features- “Noonan look” - Epilepsy Scoliosis - Psuedoarthrosis of tibia (cyst– fracture prone)
Learning difficulties
Raised BP - due to renal artery stenosis or phaechromocytoma
Neoplasia - CNS (optic gliomas), endocrine tumours, sarcomatous changes
what are the 4 principles of ethics
respect for autonomy
non malificence
benificence
justice
what type of mutations cause cancer family syndromes
germline
if there is a germline mutation in a parents egg or sperm, how will it manifest in the child
all cells affected in offspring
when should people with FAP get their colon removed
30
to what degree of relative should relatives be referred to genetics
1- 1/2
2- 1/4
3- 1/8
how would you investigate tuberous sclerosis
Clinical examination – skin signs (UV woods lamp, nails), retinal examination
Cranial MR scan
Renal ultrasound – for angiomyolipomata
Echocardiogram – for rhabdomyomas
what sit the process of the genetic clinic for cancer
Obtain detailed family history- Confirm diagnoses of cancer Risk estimation – explain basis Counselling Interventions - Increased awareness of symptoms/ signs Lifestyle – diet, smoking, oestrogen use Screening Prophylactic surgery Genetic testing – consider in high risk
what is meant by a multifactorial etiological conditions
a polygeneic genetic component interacting with environmental factors
what are common problems in multi-system disease
variable expression within families
present to many different specialities
family history often missed
what type of tissue do somatic mutations occur in
non - germline
cancer genes are intragenic - what does this mean
associated with coding DNA
how does Li- fraumeni syndrome typically present in kids
soft tissue sarcoma
what tissues do germline mutations occur in
egg or sperm
is HNPCC AD or Ar
AD
what is meant by multistep carcinogenesis
accumulation of genetic damage causes tumour with metastatic potential
what is the classic triad of tuberous sclerosis
epilepsy, learning, difficulty, skin lesions
what is the difference between FAP and HNPCC
FAP - carpet of polyps in bowel
HNPCC - small number of polyps but still high chance of cancer
in autosomal dominant inheritance, what is the chance of inheriting the mutation
50%
Is BRAC AD or Ar
AD
what benign tumour is seen in many organs in tuberous sclerosis
hamartomas
give an example of a condition with multistep carcinogenisis
colon cancer
