Genetics Flashcards
1
Q
What is mendelian inheritance?
A
When the phenotype reflects the dominant gene
2
Q
What are autosomes?
A
Non-sex chromosomes
3
Q
What are the different types of chromosome disorders?
A
Deletion Duplication Translocation Trisomy Mosaicism
4
Q
What are deletion disorders?
A
Where a portion of a chromosome is missing
5
Q
What are duplication disorders?
A
Where a portion of a chromosome is duplicated
6
Q
What is an example of a duplication disorder?
A
Charcot-Marie-Tooth
7
Q
What are translocation disorders?
A
Where a portion of one chromosome is directly swapped with a portion of another chromosome
8
Q
What are the two types of translocation disorder?
A
Reciproocal and nonreciprocal
9
Q
What are reciprocal vs nonreciprocal translocation dsorders?
A
Reciprocal= Balanced swap between chromosomes Nonreciprocal= where a portion of one chromosome leaves the first chromosome and attaches to another without an exchange
10
Q
What do translocation disorders usually lead to?
A
Predisposes to other conditions such as cancer and infertility
11
Q
What is an example of a translocation disorder?
A
Philadelphia chromosome translocation in acute myeloid leukamia: reciprocal translocation between chromosome 9 and 22
12
Q
What are Robertsonian translocations?
A
Those that occur in acrocentric chromosomes: lose the short arm completely and two long arms connect at the centromere.
13
Q
What are acrocentric chromosomes?
A
Chromosomes 13, 14, 15, 21 and 22.
Have a long arm which contains most of the genetic material and a very short arm with little genetic information
14
Q
What is trisomy?
A
When the person has an extra chromosome (47 in total)
15
Q
What three conditions are caused by trisomy?
A
Patau syndrome
Edwards syndrome
Down’s syndrome
16
Q
What chromosome is affected in Patau syndrome and what are the symptoms?
A
Trisomy 13: dysmorphic features, structural abnormalities all over body and learning disability. Characteristic ‘rocker bottom feet’
17
Q
What chromosome is affected in Edward’s syndrome and what are the symptoms?
A
Trisomy 18
Varies in severity
Also have ‘rocker bottom feet’
18
Q
What chromosome is affected in Down’s syndrome?
A
Trisomy 21
19
Q
What is mosaicism?
A
Where the chromosomal abnormality happens after conception. The person therefore has different genetic material in different cells in their body as only some cells are affected/
20
Q
What are mitochondrial myopathias?
A
Rare cases where abnormal mitochondira lead to poor production of ATP. This leads to myopathy (abnormal muscle function).
21
Q
Where does mitochondrial inheritance come from?
A
The mother
22
Q
When would genetic testing be used?
A
Diagnostic testing
Predictive testing
Carrier testing
(Genealogical testing, forensic testing, paternity testing)
23
Q
When is diagnostic testing used?
A
When a fetus or person has a suspected genetic condition (e.g. antenatal testing for Down’s syndrome)
24
Q
How do you test a fetus for a genetic condition?
A
Amniocentesis
25
What is predictive testing? (+example?)
Testing someone for a specific gene mutation that may have inplications for them in the future. e.g. BRCA1 breast cancer gene
26
What is carrier testing?
Testing potential parents for a specific autosomal recessive condition to calculate the risk of them passing it to their children
27
What is karyotyping?
Looking at the number of chromosomes, their size and structures
28
When would karyotyping be used?
To diagnose chromosomal conditions such as donw's syndrome and turner syndome
29
What is microarray testing?
Cutting up the genetic material using enzymes, then putting it onto a plate that separates the molecules by different weights to see what genes the person expresses
30
When would microarray testing be used?
To diagnose things with specific genes (e.g. Cystic fibrosis)
Screening for chromosomal abnormalities and common genetic conditions
Looking for mutations in cancer cells
31
How is specific gene testing done?
By splitting two strands of DNA and adding a 'gene probe'- single stranded DNA that contains complementary genetic code for a specific gene you want to test for.
32
When is DNA sequencing used?
For research purposes
33
What causes Down's syndrome?
Three copies of chromosome 21
34
What are the characteristic dysmorphic features seen in Down's syndrome?
```
Hypotonia
Brachycephaly
Short neck
Short stature
Flattened face and nose
Prominent epicanthic folds
Upward sloping palpebral fissures
Single palmar crease
```
35
What is brachycephaly?
Small head with flat back
36
What are epicanthic folds?
The folds of skin covering the medial portion of the eyelid and eye
37
What are palpebral fissures?
Gaps between the lower and upper eyelid
38
What are the key potential complications of Down's syndrome?
```
Learning disability
Recurrent otitis media
Deafness/ eustachian tube abnormalities
Visual problems
Hypothyroidism
Cardiac defects
Atlantoaxial instability
Increased risk of leukaemia
Dementia
```
39
Who is offered screening for Down's syndrome?
All women
40
What is the first line screening test for Down's syndrome?
Combined test
41
Which mothers have a greater risk of Down's syndrome?
Older mothers
42
What is involved in the combined test?
Using USS to measure nuchal translucency and two maternal blood tests
43
When is the combined test performed?
11 to 14 weeks gestation
44
What is nuchal thickness and what will it be in a fetus with Down's syndrome?
The thickness of the back of the neck
| >6mm in Down's
45
What are the two maternal blood tests used in the combined test and what results would indicate greater risk of Down's?
Beta-HCG (high)
| Pregnancy-associated plasma protein-A (PAPPA) (low)
46
What is the triple test and when would it be used?
3 maternal blood tests:
Beta-HCG
Alpha-fetoprotein
Serum oestriol
Done between 14-20 weeks gestation
47
What is the quadruple test and when would it be used?
Performed between 14 and 20 weeks
| Same as triple test but also tests for inhibin-A in maternal blood
48
When would a woman be offered further testing to look for Down's?
If the risk score is greater than 1 in 150
49
What are the further antenatal testing options for Down's syndrome after initial screening?
Amniocentesis
| Chorionic villus sampling
50
What is chorionic villus sampling?
An USS guided biopsy of the placental tissue
51
What is amniocentesis?
USS guided aspiration of amniontic fluid using needle and syringe.
52
When would chorionic villus sampling be used instead of amniocentesis?
Chorionic villus sampling used before 15 weeks before there is enough amniotic fluid to take a safe sample
53
What is NIPT?
Non-invasive prenatal testing
54
What does NIPT involve?
A simple blood test from the mother which will contain fragments of DNA from the placental tissue which can be analysed to detect conditions such as Down's
55
What is the management of Down's?
```
MDT to meet needs:
OT
SALT
Phsyio
Dietician
Paediatrician
GP
Health visitors
Cardiologists
ENT/ Audologist/ Opticians
Social services
```
56
What routine checks should children with Down's syndrome get?
Regular thyroid checks (every 2 years)
Echocardiogram
Regular audiometry
Regular eye checks
57
What is the average life expectancy for Down's syndrome?
60 years
58
What is Klinefelter syndrome?
A chromosomal disorder caused by an extra X chromosome in males
59
What is the chromosomal abnormality in Klinefelter syndrome?
47 XXY
60
What are the features of Klinefelter syndrome?
```
Tall
Wide hips
Gynaecomastia
Weak muscles
Smaller testicles
Reduced libido
Shyness
Infertility
Learning difficulties
```
61
When does Klinefelter usually present?
At puberty
62
What are the management options for Klinefelter syndrome?
```
Help features of condition:
Testosterone injections
IVF to allow for fertility
Breast reduction surgery
MDT (OT, SALT, Physio)
```
63
What is the prognosis for Klinefelter syndrome?
Normal life expectancy
| Slightly increased risk of breast cancer, osteoporosis, diabetes, anxiety & depression
64
What is the chromosomal abnormality in Turner syndrome?
When a female has a single X chromosome (45 XO)
65
What are the features of Turner syndrome?
```
Short stature
Webbed neck
High arched palate
Downward sloping eyes with ptosis
Broad chest
Cubitus valgus
Underdeveloped ovaries
Late/ incomplete puberty
Infertility
```
66
What is cubitus valgus?
Abnormal elbow- forearm is angled out away from body when arm is fully extended
67
What conditions are associated with Turner syndrome?
```
Recurrent otitis media
Recurrent UTI
Coarctation of aorta
Hypothyroidism
Hypertension
Obesity
Diabetes
Osteoporosis
Learning difficulties
```
68
How is Turner syndrome managed?
GH therapy for short stature
Oestrogen and progesterone replacement to establish secondary sex characteristics
Fertility treatment
Manage associated conditions
69
What is Noonan syndrome and what is its inheritance pattern?
Autosomal dominant genetic condition caused by multiple genes
70
What are the features of Noonan syndrome?
```
Short stature
Broad forehead
Downward sloping eyes & ptosis
Hypertelorism (wide space between eyes)
Prominent nasolabial folds
Low set ears
Webbed neck
Wide spaced nipples
```
71
Does Noonan's always present the same?
No- wide variation in signs and symptoms depending on underlying cause
72
What conditions are associated with Noonans?
```
Congenital heart disease
Cryptorchidism leading to infertility
Learning disability
Bleeding disorders
Lymphoedema
Increased risk of leukaemia and neuroblastome
```
73
What is the management of Noonans?
Supportive with MDT
| Often require corrective heart surgery for congenital heart disease
74
What kind of inheritance pattern is marfan syndrome?
Autosomal dominant
75
What is the pathophysiology of Marfan syndrome?
Gene responsible for creating Fibrillin (important component of connective tissue) is affected, meaning they have abnormal connective tissue
76
What are the features of Marfan's?
```
Tall
Long neck
Long limbs
Long fingers
High arch palate
Hypermobility
Pectus carinatum or excavatum
Downward sloping palpable fissures
```
77
What is arachnodactyly and how do you test for it?
Long fingers
1. Cross thumb across palm to see if it goes past opposite edge of hand
2. Wrap thumb and fingers around opposite wrist to see if thumb and fingers overlap
78
What are the associated conditions with Marfan's?
```
Lens discoloration
Joint dislocations and pain
Scoliosis
Pneumothorax
GORD
Mitral valve prolapse (with regurgitation)
Aortic valve prolapse (with regurgitation)
Aortic aneurysms
```
79
What is the management of Marfans?
Surgical correction of any cardiac complications
Minimise blood pressure and heart rate (lifestyle changes, preventative medications)
Physiotherapy
Genetic counselling
Yearly echocardiograms and opthalmologist review
80
What causes fragile X syndrome?
Mutation in the FMR1 gene on the X chromosome
81
What does the FMR1 gene code for?
Fragile X mental retardation protein- plays a role in cognitive development in the brain
82
What is the inheritance pattern of fragile X syndrome?
X-linked (unknown if dominant or recessive)
83
What are the features of fragile X syndrome?
```
Delay in speech and language development
Intellectual disability
Long, narrow face
Large ears
Large testicles
Hypermobile joints
ADHD
Autism
Seizures
```
84
What is Prader-Willi syndrome?
Genetic condition caused by loos of functional genes on proximal arm of chromosome 15 inherited from father.
85
What are the features of Prader-WIlli syndrome?
```
Constant insatiable hunger
Hypotonia
Mild learning disability
Hypogonadism
Fairer, soft skin prone to bruising
Mental health problems
Dysmorphic features
Narrow forehead
Almond shaped eyes
Strabismus
Thin upper lip
Downturned mouth
```
86
How is Prader-Willi syndrome managed?
Dietician with limited access to food
GH to improve muscle development and body composition
MDT
87
What is Angelman syndrome?
Genetic condition caused by loss of function in UBE3A gene inherited from mother
88
What are the features of angelman syndrome?
```
Delayed development
Learning disability
Delay/ absence of speech development
Ataxia
Fascination with water
Happy demeanour
Inappropriate laughter
Hand flapping
Wide spaced teeth
Abnormal sleep patterns
Epilepsy
ADHD
Dysmorphic deatures
Microcephaly
Fair skin, light hair, blue eyes
```
89
What are the features of angelman syndrome?
```
Delayed development
Learning disability
Delay/ absence of speech development
Ataxia
*Fascination with water
*Happy demeanour
Inappropriate laughter
Hand flapping
Wide spaced teeth
Abnormal sleep patterns
Epilepsy
ADHD
Dysmorphic deatures
Microcephaly
Fair skin, light hair, blue eyes
```
90
How is Angelman syndrome managed?
MDT to support patient holistically and manage individual problems.
91
What is William syndrome?
Deletion of genetic material on one copy of chromosome 7 (random deletion around conception)
92
What are the features of William syndrome?
```
Broad forehead
*Starburst eyes
Flattened nasal bridge
Long philtrum
*Wide mouth with wide spaced teeth
Small chin
*Sociable, trusting personality
Mild learning disability
```
93
What conditions are associated with William syndrome?
Supravalvular aortic stenosis
ADHD
Hypertension
Hypercalcaemia
94
What is the management of William syndrome?
MDT
Echo's and BP monitoring to assess for aortic stenosis and hypertension
Low calcium diet to control hypercalcaemia
