Genetics Flashcards
3 major patterns of inheritance
autosomal dominant
autosomal recessive
X linked
If someone has an AD gene, what chance does the child have of inheriting?
50%
What inheritance is hereditary haemochromatosis
AR
When both parents are carriers of AR genes, what chance does the child have of being affected and being a carrier?
25% affected
50% carrier
Who does X linked inheritance most commonly affect
Males
Why can X linked inheritance not pass from father to son?
an affected father only passes on a Y chromosome to his sons
Explanations of X linked inheritanc
No male to male tranmission (father passes Y chromosome only to his sons)
Daughters of an affected male are obligate carriers (an affected father passes his X chromosomes to all of his daughters)
Sons of a female carrier have a 50% chance of being affected and daughters have 50% chance of being carriers
What are haemophilias
Inherited clotting disorders which vary in severity according to the relative deficiency of the clotting factor concerned
Cause of haemophilia A
Reduced synthesis of Factor VIII
Cause of haemophilia B
Deficiency of Factor IX
Inheritance of haemophilias
X linked (recessive)
Generally affecting males born to female carriers
Some women who carry the haemophilia gene may have what?
Prolongation of APTT
Where can acquired haemophilia be seen?
Systemic inflammatory conditions such as RA because of the anti-factor VIII antibodies
How much of haemophilias are not familial i.e. sporadic?
30%
Differentials of haemophilia
DIC
Vit K deficiency
Disorders of fibrinogen or fibrinolytic production
Platelet disorders
Von Willebrands disease
Coag of haemophilias
Prolonged APTT
Normal PT and VWF
Treatment of haemophilia
Factor VIII/IX concentrate infusion
Acquired Factor VIII defieincy in mild cases - desmopressin or factor VIII in severe bleeding
Synthetic vasopressin
Fibrinolytic inhibitors
Vaccination against Hep B
Inheritance of familial hypercholesteraemia
AD
What criteria is used to aid diagnosis of familial hypercholesteraemia
Simon Boome criteria
Features of primary hypertriglyceraemia (without hypercholesteraemia)
Elevated very low density lipoprotein (Which confers even greater risk than LDL)
Present in childhood with eruptive xanthomas , lipaemia retinalis, retinal vein thrombosis, pancreatitis and hepatosplenomegaly
What can be detected in fasting plasma with primary hypertriglycaemia without hypercholestermaemia
Chylomicrons
Feautures of primary mixed (or combined) hyperlipidaemia
Elevated cholesterol and triglycerides
There is premature atherosclerosis
Assosiated with apoprotein E2 (high CV risk)
Remnant hyperlipidaemia is a rare cause - palmar xanthomas and tuberous xathomas over knees and elbows is characteristic
Diagnosis of FH
Lipid profile (two measurements)
Signs such as tendon xanthomata
Exclude secondary causes
What DNA evidence could prove FH
LDL receptor mutation
Familial defective apolipoprotein B100
PCSK9 mutation
Inheritance of hereditary angioedema
AD
Diagnosis in blood of hereditary angioedema
C4 level - if low then measure C1-INH
C4 levels remain persistently low even in between attacks
Inheritance tuberous sclerosis
AD inherited disorder
Variable expression
Can result from new mutations
Presentation tuberous sclerosis
Epilepsy in infancy or childhood
LDs
Oviod hypopigmented macules
Facial angiofibromata
Periungal fibromata
Shagreen patch on lower back
Retinal hamartoma
Inheritance of huntingtons
AD
Features of Albrights hereditary osteodystropgy
Short stature
Brachydactyly
Soft tissue calcification
Psudohyperparathyroidism
Hypothryoidism
Ovarian failure
Features of pseudohyperparathyroidism
Severe hypocaclcaemia
Elevated PTH
Features of tuberous sclerosis
LDs
Infantile spasms
Seizures
Hyrocephaly secondary to cerebral glial nodules
Facial angiofibroma
Adenoma sebaceum
Ash leaf shaped macules
Shagreen patches
Depigmented naevi
Subcutaneous nodules
Cafe au lait spots
Subungual fibromas on nails
Teeth - pitted enamel hypoplasia
Chromatic retinal patches
Retinal tumours
Hypopigmented iris spots
Tumours
Renal cysts
HTN
Aortic aneurysm
Tumours common in tuberous sclerosis
Myocardial rhabdomyoma
Multiple bilateral renal angiomyolipoma
Wilms tumour
Cardiac and olfactory hamartomas
Ependyoma and astrocytoma
Features of cryoglobulinaemia
Arthralgia
Purpura
Skin ulcers
Glomerulonephritis
Peripheral neuropathy
Assosiations of cryogloblinaemia
Hep C
HIV
Monoclonal gammopathy
Connective tissue disease
What is cryoglobulinaemia
Prescence of cryoglobulins (immunoglobulins and/or complement components that precipitate at temps lower than 37C and dissolve on rewarming) in the serum
Treatment of cryoglobulinaemia
No specific treatment
Underlying condition should be treated
Inheritance of HHT
AD
Features of HHT
Telengectasias
Recurrent bleeding episodes
GI haemorrhage
Stroke (haemorrhagic and ischaemic)
high output cardiac failure
Features of turners syndrome
Webbing of neck
Lack of secondary sexual characteristics
Short stature
Coarctation of the aorta
Symptoms of coarctation of the aorta
Vigorous pulsation of neck or throat
HTN
Tired legs or claudication on running
LVF
Angina
Aortic rupture
Features of homocystinuria
Marfanoid habitus
Low IQ
DOWNWARD dislocation of the lens
Increased risk of VTE and MI
Gene dysfunction in homocytinuria
Cystathionine beta synthase deficiency
Inheritence of lebers hereditary optic neuropathy
Mitochondrial
(men cannot pass to any offspring, because all mitochondrial genes are inherited from the woman)
When to consider an abnormal grief reaction (timeframe)
> 6 months
Women with HNPCC are at risk of what cancers
- Endometrial
- CRC
- Ovarian
Inheritance of a1aT deficiency
Autosomal co-dominant
HLA assosiation of bechets disease
HLAB51
Genetic mutation of HNPCC
MutL homolog 1 gene mutation
Features of lebers hereditary optic neuropathy
Begins with progressive unilateral optic neuropathy (other eye usually affected months of years afterwards)
Proximal myopathy and increased tone
Fundoscopy changes - telangiectasias and pseudo-oedema of the optic disc
Features of myotonic dystrophy type I
Predominantely affects facial muscles, forearm muscles and ankle dorsiflexors
Delayed grip relaxation
Men - frontal baldness
Myotonic dystrophy type I vs II
1 - predominately facial muscles, forearm muscles and ankle dorsiflexors
II - neck flexors and finger flexors in earlier stages
What measurement determines disease progression in MND
Sniff nasal inspiratory pressure
FVC
Urinary calcium excretion - Gietleman syndrome vs Bartters syndrome
Gietleman - low urinary excretion
Bartters - high urinary excretion
Two forms of HNPCC
Lynch I - no FH of other cancers
Lynch II - other cancers in the family e.g. endometrial, ovarian, urinary tract
