Genetics Flashcards
What is mendelian inheritance?
When the phenotype reflects the dominant gene
What are autosomes?
Non-sex chromosomes
What are the different types of chromosome disorders?
Deletion Duplication Translocation Trisomy Mosaicism
What are deletion disorders?
Where a portion of a chromosome is missing
What are duplication disorders?
Where a portion of a chromosome is duplicated
What is an example of a duplication disorder?
Charcot-Marie-Tooth
What are translocation disorders?
Where a portion of one chromosome is directly swapped with a portion of another chromosome
What are the two types of translocation disorder?
Reciproocal and nonreciprocal
What are reciprocal vs nonreciprocal translocation dsorders?
Reciprocal= Balanced swap between chromosomes Nonreciprocal= where a portion of one chromosome leaves the first chromosome and attaches to another without an exchange
What do translocation disorders usually lead to?
Predisposes to other conditions such as cancer and infertility
What is an example of a translocation disorder?
Philadelphia chromosome translocation in acute myeloid leukamia: reciprocal translocation between chromosome 9 and 22
What are Robertsonian translocations?
Those that occur in acrocentric chromosomes: lose the short arm completely and two long arms connect at the centromere.
What are acrocentric chromosomes?
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
What is trisomy?
When the person has an extra chromosome (47 in total)
What three conditions are caused by trisomy?
Patau syndrome
Edwards syndrome
Down’s syndrome
What chromosome is affected in Patau syndrome and what are the symptoms?
Trisomy 13: dysmorphic features, structural abnormalities all over body and learning disability. Characteristic ‘rocker bottom feet’
What chromosome is affected in Edward’s syndrome and what are the symptoms?
Trisomy 18
Varies in severity
Also have ‘rocker bottom feet’
What chromosome is affected in Down’s syndrome?
Trisomy 21
What is mosaicism?
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/
What are mitochondrial myopathias?
Rare cases where abnormal mitochondira lead to poor production of ATP. This leads to myopathy (abnormal muscle function).
Where does mitochondrial inheritance come from?
The mother
When would genetic testing be used?
Diagnostic testing
Predictive testing
Carrier testing
(Genealogical testing, forensic testing, paternity testing)
When is diagnostic testing used?
When a fetus or person has a suspected genetic condition (e.g. antenatal testing for Down’s syndrome)
How do you test a fetus for a genetic condition?
Amniocentesis
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
What is carrier testing?
Testing potential parents for a specific autosomal recessive condition to calculate the risk of them passing it to their children
What is karyotyping?
Looking at the number of chromosomes, their size and structures
When would karyotyping be used?
To diagnose chromosomal conditions such as donw’s syndrome and turner syndome
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
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
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.
When is DNA sequencing used?
For research purposes
What causes Down’s syndrome?
Three copies of chromosome 21
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
What is brachycephaly?
Small head with flat back
What are epicanthic folds?
The folds of skin covering the medial portion of the eyelid and eye
What are palpebral fissures?
Gaps between the lower and upper eyelid
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
Who is offered screening for Down’s syndrome?
All women
What is the first line screening test for Down’s syndrome?
Combined test
Which mothers have a greater risk of Down’s syndrome?
Older mothers
What is involved in the combined test?
Using USS to measure nuchal translucency and two maternal blood tests
When is the combined test performed?
11 to 14 weeks gestation
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
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)
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
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
When would a woman be offered further testing to look for Down’s?
If the risk score is greater than 1 in 150
What are the further antenatal testing options for Down’s syndrome after initial screening?
Amniocentesis
Chorionic villus sampling
What is chorionic villus sampling?
An USS guided biopsy of the placental tissue
What is amniocentesis?
USS guided aspiration of amniontic fluid using needle and syringe.
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
What is NIPT?
Non-invasive prenatal testing
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
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
What routine checks should children with Down’s syndrome get?
Regular thyroid checks (every 2 years)
Echocardiogram
Regular audiometry
Regular eye checks
What is the average life expectancy for Down’s syndrome?
60 years
What is Klinefelter syndrome?
A chromosomal disorder caused by an extra X chromosome in males
What is the chromosomal abnormality in Klinefelter syndrome?
47 XXY
What are the features of Klinefelter syndrome?
Tall Wide hips Gynaecomastia Weak muscles Smaller testicles Reduced libido Shyness Infertility Learning difficulties
When does Klinefelter usually present?
At puberty
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)
What is the prognosis for Klinefelter syndrome?
Normal life expectancy
Slightly increased risk of breast cancer, osteoporosis, diabetes, anxiety & depression
What is the chromosomal abnormality in Turner syndrome?
When a female has a single X chromosome (45 XO)
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
What is cubitus valgus?
Abnormal elbow- forearm is angled out away from body when arm is fully extended
What conditions are associated with Turner syndrome?
Recurrent otitis media Recurrent UTI Coarctation of aorta Hypothyroidism Hypertension Obesity Diabetes Osteoporosis Learning difficulties
How is Turner syndrome managed?
GH therapy for short stature
Oestrogen and progesterone replacement to establish secondary sex characteristics
Fertility treatment
Manage associated conditions
What is Noonan syndrome and what is its inheritance pattern?
Autosomal dominant genetic condition caused by multiple genes
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
Does Noonan’s always present the same?
No- wide variation in signs and symptoms depending on underlying cause
What conditions are associated with Noonans?
Congenital heart disease Cryptorchidism leading to infertility Learning disability Bleeding disorders Lymphoedema Increased risk of leukaemia and neuroblastome
What is the management of Noonans?
Supportive with MDT
Often require corrective heart surgery for congenital heart disease
What kind of inheritance pattern is marfan syndrome?
Autosomal dominant
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
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
What is arachnodactyly and how do you test for it?
Long fingers
- Cross thumb across palm to see if it goes past opposite edge of hand
- Wrap thumb and fingers around opposite wrist to see if thumb and fingers overlap
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
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
What causes fragile X syndrome?
Mutation in the FMR1 gene on the X chromosome
What does the FMR1 gene code for?
Fragile X mental retardation protein- plays a role in cognitive development in the brain
What is the inheritance pattern of fragile X syndrome?
X-linked (unknown if dominant or recessive)
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
What is Prader-Willi syndrome?
Genetic condition caused by loos of functional genes on proximal arm of chromosome 15 inherited from father.
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
How is Prader-Willi syndrome managed?
Dietician with limited access to food
GH to improve muscle development and body composition
MDT
What is Angelman syndrome?
Genetic condition caused by loss of function in UBE3A gene inherited from mother
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
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
How is Angelman syndrome managed?
MDT to support patient holistically and manage individual problems.
What is William syndrome?
Deletion of genetic material on one copy of chromosome 7 (random deletion around conception)
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
What conditions are associated with William syndrome?
Supravalvular aortic stenosis
ADHD
Hypertension
Hypercalcaemia
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
