Genetics Flashcards
when are women offered the combined test? and what findings indicate high risk?
11-14 weeks
- USS of nuchal transucency > 6mm (thickness due to fluid behind the neck)
- bHG -. ==> high
- plasma protein A ==> low
what is measured in the triple and quadruple test for downs syndrome, what would indicates a positive test and when would they be carried out?
14-20 weeks
- Alpha feotprotien (AFP) -> LOW
- Serum oestriol - LOW
- beta HCG -> HIGH
— +
- inhibin A -> HIGH
a non-invasive test for downs syndrome
NIPT
non-invasive prenatal testing using the mothers blood
not definitive though!
neuromas in NF1 are benign
a. true
b. false
a. true
but cause neurological issues and structural problems
NF1 mode of inheritance
autosomal dominant
17q11.2 gene (tumour supressor)
key features of NF1 (diagnostic NIH)
cafe au lait spots (6+)
neurofibromas (2+)
lisch nodules (specs in the iris)
axillary freckling
optic glioma (lump on optic nerve)
bone defects
scoliosis (early childhood)
family history
2+ needed
NF1 increases the risk of what other illnesses?
malignancy
optic gliomas
scoliosis
learning disabilities
what else in important to screen for in people with NF1?
PHEOCHROMOCYTOMA - ADRENAL TUMOUR
RENAL ARTERY STENOSIS
check BP!!!
CRABBING features of NF1
Cafe au lait spots >6
Relative with NF1 (dominant)
Axillary or inguinal freckles
Bony dysplasia (bowing of long bones)
Iris -lisch nodules - yellow or brown spots in the iris
Neurofibromas
Glioma of optic nerve
what type of tumours in NF2
schwannomas (on scwhann cells)
bilateral acoustic neuromas are 100% what?
NF2
symptoms of NF2
Bilateral vestibular schwannomas (tumors on the auditory nerve)
- Hearing loss
- Cataracts
- Meningiomas
inheritance of duchennes muscular dystrophy
x-linked recessive
symptoms of duchenne mucuslar dystrophy
Progressive muscle weakness,
Gower’s sign,
calf pseudohypertrophy
early mortality
learning disabilities
how is myotonic dystrophy inherited
autosominal dominant
symtoms of myotonic dsytrophy
Muscle wasting, cataracts, diabetes,
myotonia (delayed muscle relaxation after voluntary contraction - e.g. muscles remain tense after gripping object)
-> worse in COLD temperatures
PERIPHERAL muscles - hands, forearms, neck, feet, calves
what can be the first sign of myotonic dystrophy in a family
cataracts before 40
examination findings in myotonic dyststrophy
frontal balding
cataracts
long thin face (myopathic facies)
speech - dsarthria (myotonic tongue) and pharyngeal muscles
neck - wasting of SCM
distal muscle wasting
repeats of CTG within DMPK gene
myotonic dystrophy
heart defects associated with downs syndrome
ASD
VSD
septal defects!!
downs syndrome are at increased risk of
early alzhiemers
ALL - leaukamia
Extra chromosome 18
edwards syndrome
features of edwards syndrome
Clenched fists,
rocker-bottom feet,
overlapping fingers
severe intellectual disability
kidney defects
Extra chromosome 13
Trisomy 13 (Patau Syndrome)
22q11.2 deletion
DiGeorge Syndrome
heart defects associated with DiGeorge Syndrome
Tetralogy of Fallot,
catch 22 for digeorge syndrome
C : Cardiac defects – Congenital heart defects, especially Tetralogy of Fallot, truncus arteriosus, interrupted aortic arch.
A Abnormal facies – Low-set ears, small mouth, hypertelorism (wide-set eyes), micrognathia (small jaw).
T Thymic hypoplasia – Leads to T-cell immunodeficiency, increasing infection risk.
C Cleft palate – Causes feeding and speech difficulties.
H Hypocalcemia – Due to parathyroid hypoplasia, leading to muscle spasms, seizures.
22 Chromosome 22q11.2 deletion – The underlying genetic cause.
heart defects associated with turners syndrome
Coarctation of the aorta,
bicuspid aortic valve
features of turners syndrome (appearance)
Short stature,
webbed neck,
broad chest
short fingers
associated with
a lack of smell + delayed puberty
kallmans syndrome
47,XXY
Klinefelter Syndrome Extra X chromosome in males
features of klinefelter syndrome
Tall stature, gynecomastia, hypogonadism
47,XXY
inhertiance of tuberous sclerosis complex *TSC
autosominal dominant
or new mutations
Seizures (infantile spasms, myoclonic seizures)
intellectual disability (common to ASD)
skin lesions (depigmented macules)
TRIAD is indicative of what autosomal dominant condition
tuberous scleorosis complex
-
cardiac features of tuberous scelorous complex
rhabdomyomas (cardiac tumours) - bengin
angiofibromas (raised pink lesions on skin)
angiomyolipomata (benigin lesions in kidney/cysts)
phakomas in eye
angiomyolipomas (renal lesions) and rhabomyomas (cardiac tumours) can be seen in
tuberous scelrorsis complex
+ epilepsy
+ learning difficulties
signs of ALS
upper and lower motor neuron
- progressive weakness
wasting of muscles
increased reflexes
limb and bulbar muscle (Swallowing muscle weakness)
pure motor signs (Fasiculations)
cognition is spared
stiff muscles, muscle twitching, worsening weakness due to muscle wasting
HTT gene (CAG repeats) causes
Huntington’s Disease (autosomal dominant)
huntingtons symptoms
Chorea (uncontrolled movements),
psychiatric symptoms (depression, paranoia , psychosis)
dementia
Progressive neurodegeneration, weight loss
personality changes/cognitive changes
FBN1 mutation (fibrillin)1
Marfan Syndrome
autosomal dominant
Tall stature, hypermobile joints, lens dislocation,Arachnodactyly (long fingers), scoliosis
marfans
Hyperextensible skin, joint hypermobility
EDS
heart problems associated with marfans
Aortic aneurysm/dissection,
mitral valve prolapse
cystic fibrosis is associated with finger clubbing
a.true
b. false
a. true
meconium ileus
infertility (missing ductus deferns)
pancreatic insufficecny
chronic lung infections
Early emphysema (COPD-like symptoms), liver disease Pulmonary hypertension (in severe cases) Liver cirrhosis, increased risk of hepatocellular carcinoma
Alpha-1 Antitrypsin Deficiency
autosomal dominant
APC gene mutation that causes increase in GI cancer
Familial Adenomatous Polyposis (FAP)
Hundreds to thousands of colonic polyps, high colorectal cancer risk
MLH1, MSH2, MSH6, PMS2 mutations that increases risk of early onset colo-rectal cancer
mistmatch repair genes MLH1 and MLH2
Hereditary Nonpolyposis Colorectal Cancer (HNPCC, Lynch Syndrome)
Early-onset colorectal cancer (45 years old), endometrial & ovarian cancer
Few to no polyps, risk of stomach/renal cancers
autosominal dominant
cancer arises in proximal colon - symptoms are less obivious /late
BRACA 1 and 2 increase risk of
breast
ovarian
Braca 2 -> prostate in men
turners syndrome is a cause of primary ammenorhoea
a.true
b. false
a. true
what are germline mutations
inherited from a single alteration in egg or sperm
are heritable
cause family cancer syndromes
what are somatic mutations
non-germline
non-inheritatble
two X hits to individual cells -> most cancers
1 hit to oncogene is enough to cause cancer (cells that regulate cell growth)
genotype
refers to the two alleles (A.A)
phenotype
refers to the physical traits
A single mutated gene from one parent is enough to cause disease
Autosomal Dominant (AD)
- Marfan Syndrome
- Huntington’s Disease
- ## Neurofibromatosis (NF1, NF2)
are examples of what inheritance
Autosomal Dominant (AD) A single mutated gene from one parent is enough to cause disease.
- Affected individuals in every generation (“vertical inheritance”).
- 50% chance of passing to offspring if one parent is affected.
Two copies of the mutated gene (one from each parent) are needed to cause disease.
Autosomal Recessive (AR)
Cystic Fibrosis (CF)
- Sickle Cell Disease
- Phenylketonuria (PKU)
- Tay-Sachs Disease
- Alpha-1 Antitrypsin Deficiency
examples of what mode of inheritance
Autosomal Recessive (AR) Two copies of the mutated gene (one from each parent) are needed to cause disease.
- Often skips generations (“horizontal inheritance”).
- Carriers (heterozygotes) are asymptomatic.
- 25% chance of affected child if both parents are carriers.
Autosomal Recessive (AR) Two copies of the mutated gene (one from each parent) are needed to cause disease.
Mutation on the X chromosome. Males (XY) need only one copy to be affected; females (XX) need two copies.
X-Linked Recessive
- Duchenne Muscular Dystrophy (DMD)
- Hemophilia A & B
- G6PD Deficiency
- Red-Green Color Blindness
mode of inheritance?
X-Linked Recessive (XLR) Mutation on the X chromosome. Males (XY) need only one copy to be affected; females (XX) need two copies.
Mutation on the X chromosome; only one copy is needed to cause disease.
X-Linked Dominant (XLD)
- Rett Syndrome
- Fragile X Syndrome
- Incontinentia Pigmenti
- Alport Syndrome
what mode of inheritance
X-Linked Dominant (XLD)
Mutation in mitochondrial DNA, inherited only from the mother (since sperm do not contribute mitochondria).
Mitochondrial (Maternal) Inheritance
- Passed only from mother to offspring.
- Affected mothers pass mutation to ALL children (100%), but only daughters can transmit further.
- Variable severity due to heteroplasmy (cells may have a mix of normal and mutant mitochondria).
Mitochondrial (Maternal) Inheritance
