Genetics

Question 1

when are women offered the combined test? and what findings indicate high risk?

Answer 1

11-14 weeks

1. USS of nuchal transucency > 6mm (thickness due to fluid behind the neck)
2. bHG -. ==> high
3. plasma protein A ==> low

Question 2

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?

Answer 2

14-20 weeks

• Alpha feotprotien (AFP) -> LOW
• Serum oestriol - LOW
• beta HCG -> HIGH

— +
- inhibin A -> HIGH

Question 3

a non-invasive test for downs syndrome

Answer 3

NIPT

non-invasive prenatal testing using the mothers blood

not definitive though!

Question 4

neuromas in NF1 are benign

a. true
b. false

Answer 4

a. true

but cause neurological issues and structural problems

Question 5

NF1 mode of inheritance

Answer 5

autosomal dominant

17q11.2 gene (tumour supressor)

Question 6

key features of NF1 (diagnostic NIH)

Answer 6

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

Question 7

NF1 increases the risk of what other illnesses?

Answer 7

malignancy

optic gliomas

scoliosis

learning disabilities

Question 8

what else in important to screen for in people with NF1?

Answer 8

PHEOCHROMOCYTOMA - ADRENAL TUMOUR

RENAL ARTERY STENOSIS

check BP!!!

Question 9

CRABBING features of NF1

Answer 9

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

Question 10

what type of tumours in NF2

Answer 10

schwannomas (on scwhann cells)

Question 11

bilateral acoustic neuromas are 100% what?

Answer 11

NF2

Question 12

symptoms of NF2

Answer 12

Bilateral vestibular schwannomas (tumors on the auditory nerve)
- Hearing loss
- Cataracts
- Meningiomas

Question 13

inheritance of duchennes muscular dystrophy

Answer 13

x-linked recessive

Question 14

symptoms of duchenne mucuslar dystrophy

Answer 14

Progressive muscle weakness,

Gower’s sign,

calf pseudohypertrophy

early mortality

learning disabilities

Question 15

how is myotonic dystrophy inherited

Answer 15

autosominal dominant

Question 16

symtoms of myotonic dsytrophy

Answer 16

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

Question 17

what can be the first sign of myotonic dystrophy in a family

Answer 17

cataracts before 40

Question 18

examination findings in myotonic dyststrophy

Answer 18

frontal balding

cataracts

long thin face (myopathic facies)

speech - dsarthria (myotonic tongue) and pharyngeal muscles

neck - wasting of SCM

distal muscle wasting

Question 19

repeats of CTG within DMPK gene

Answer 19

myotonic dystrophy

Question 20

heart defects associated with downs syndrome

Answer 20

ASD

VSD

septal defects!!

Question 21

downs syndrome are at increased risk of

Answer 21

early alzhiemers

ALL - leaukamia

Question 22

Extra chromosome 18

Answer 22

edwards syndrome

Question 23

features of edwards syndrome

Answer 23

Clenched fists,

rocker-bottom feet,

overlapping fingers

severe intellectual disability

kidney defects

Question 24

Extra chromosome 13

Answer 24

Trisomy 13 (Patau Syndrome)

Question 25

22q11.2 deletion

Answer 25

DiGeorge Syndrome

Question 26

heart defects associated with DiGeorge Syndrome

Answer 26

Tetralogy of Fallot,

Question 27

catch 22 for digeorge syndrome

Answer 27

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.

Question 28

heart defects associated with turners syndrome

Answer 28

Coarctation of the aorta, bicuspid aortic valve

Question 29

features of turners syndrome (appearance)

Answer 29

Short stature, webbed neck, broad chest short fingers

Question 30

associated with a lack of smell + delayed puberty

Answer 30

kallmans syndrome

Question 31

47,XXY

Answer 31

Klinefelter Syndrome Extra X chromosome in males

Question 32

features of klinefelter syndrome

Answer 32

Tall stature, gynecomastia, hypogonadism 47,XXY

Question 33

inhertiance of tuberous sclerosis complex *TSC

Answer 33

autosominal dominant or new mutations

Question 34

Seizures (infantile spasms, myoclonic seizures) intellectual disability (common to ASD) skin lesions (depigmented macules) TRIAD is indicative of what autosomal dominant condition

Answer 34

tuberous scleorosis complex -

Question 35

cardiac features of tuberous scelorous complex

Answer 35

rhabdomyomas (cardiac tumours) - bengin angiofibromas (raised pink lesions on skin) angiomyolipomata (benigin lesions in kidney/cysts) phakomas in eye

Question 36

angiomyolipomas (renal lesions) and rhabomyomas (cardiac tumours) can be seen in

Answer 36

tuberous scelrorsis complex + epilepsy + learning difficulties

Question 37

signs of ALS

Answer 37

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

Question 38

HTT gene (CAG repeats) causes

Answer 38

Huntington’s Disease (autosomal dominant)

Question 39

huntingtons symptoms

Answer 39

Chorea (uncontrolled movements), psychiatric symptoms (depression, paranoia , psychosis) dementia Progressive neurodegeneration, weight loss personality changes/cognitive changes

Question 40

FBN1 mutation (fibrillin)1

Answer 40

Marfan Syndrome autosomal dominant

Question 41

Tall stature, hypermobile joints, lens dislocation,Arachnodactyly (long fingers), scoliosis

Answer 41

marfans

Question 42

Hyperextensible skin, joint hypermobility

Answer 42

EDS

Question 43

heart problems associated with marfans

Answer 43

Aortic aneurysm/dissection, mitral valve prolapse

Question 44

cystic fibrosis is associated with finger clubbing a.true b. false

Answer 44

a. true meconium ileus infertility (missing ductus deferns) pancreatic insufficecny chronic lung infections

Question 45

Early emphysema (COPD-like symptoms), liver disease Pulmonary hypertension (in severe cases) Liver cirrhosis, increased risk of hepatocellular carcinoma

Answer 45

Alpha-1 Antitrypsin Deficiency autosomal dominant

Question 46

APC gene mutation that causes increase in GI cancer

Answer 46

Familial Adenomatous Polyposis (FAP) Hundreds to thousands of colonic polyps, high colorectal cancer risk

Question 47

MLH1, MSH2, MSH6, PMS2 mutations that increases risk of early onset colo-rectal cancer ## Footnote mistmatch repair genes MLH1 and MLH2

Answer 47

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 ## Footnote cancer arises in proximal colon - symptoms are less obivious /late

Question 48

BRACA 1 and 2 increase risk of

Answer 48

breast ovarian Braca 2 -> prostate in men

Question 49

turners syndrome is a cause of primary ammenorhoea a.true b. false

Answer 49

a. true

Question 50

what are germline mutations

Answer 50

inherited from a single alteration in egg or sperm are heritable cause family cancer syndromes

Question 51

what are somatic mutations

Answer 51

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)

Question 52

genotype

Answer 52

refers to the two alleles (A.A)

Question 53

phenotype

Answer 53

refers to the physical traits

Question 54

A single mutated gene from one parent is enough to cause disease

Answer 54

Autosomal Dominant (AD)

Question 55

- Marfan Syndrome - Huntington’s Disease - Neurofibromatosis (NF1, NF2) - are examples of what inheritance

Answer 55

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.

Question 56

Two copies of the mutated gene (one from each parent) are needed to cause disease.

Answer 56

Autosomal Recessive (AR)

Question 57

Cystic Fibrosis (CF) - Sickle Cell Disease - Phenylketonuria (PKU) - Tay-Sachs Disease - Alpha-1 Antitrypsin Deficiency examples of what mode of inheritance

Answer 57

Autosomal Recessive (AR) Two copies of the mutated gene (one from each parent) are needed to cause disease.

Question 58

- Often skips generations ("horizontal inheritance"). - Carriers (heterozygotes) are asymptomatic. - 25% chance of affected child if both parents are carriers.

Answer 58

Autosomal Recessive (AR) Two copies of the mutated gene (one from each parent) are needed to cause disease.

Question 59

Mutation on the X chromosome. Males (XY) need only one copy to be affected; females (XX) need two copies.

Answer 59

X-Linked Recessive

Question 60

- Duchenne Muscular Dystrophy (DMD) - Hemophilia A & B - G6PD Deficiency - Red-Green Color Blindness mode of inheritance?

Answer 60

X-Linked Recessive (XLR) Mutation on the X chromosome. Males (XY) need only one copy to be affected; females (XX) need two copies.

Question 61

Mutation on the X chromosome; only one copy is needed to cause disease.

Answer 61

X-Linked Dominant (XLD)

Question 62

- Rett Syndrome - Fragile X Syndrome - Incontinentia Pigmenti - Alport Syndrome what mode of inheritance

Answer 62

X-Linked Dominant (XLD)

Question 63

Mutation in mitochondrial DNA, inherited only from the mother (since sperm do not contribute mitochondria).

Answer 63

Mitochondrial (Maternal) Inheritance

Question 64

- 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).

Answer 64

Mitochondrial (Maternal) Inheritance