Genetics Flashcards
What is Klinefelter syndrome?
When a male has an additional X chromosome making them 47 XXY instead of 46 XY.
Sx of Klinefelter syndrome?
Usually males look normal until puberty where they can develop:
* Taller height
* Wider hips
* Gynaecomastia
* Weaker muscles
* Small testicles
* Reduced libido + infertility
* Shyness
Mx of Klinefelter syndrome?
- Testosterone injections
- Breast reduction surgery - cosmetic purposes
Prognosis + complications of Klinefelter syndrome?
Life expectancy = normal
Inc. risk of:
* Breast cancer (compared to other males)
* Osteoporosis
* Diabetes
* Anxiety + depression
What is Turner syndrome?
When a female has a single X chromosome making it 45 XO instead of 46 XX.
O = empty space where other X chromosome should be.
Sx of Turner syndrome?
- Short stature
- Webbed neck
- Widely spaced nipples
- High arching palate
- Downward sloping eyes w/ptosis
- Cubitus valgus (abnormal elbow feature)
- Infertility
Associated cdtns with Turner syndrome?
- Recurrent otitis media
- Recurrent UTI
- Coarctation of the aorta
- Hypothyroidism
- HTN
- Obesity
- Diabetes
- Osteoporosis
Mx of Turner syndrome?
- Growth hormone therapy - prevent short stature
- Oestrogen + progesterone replacement - establish female characteristics + regulate period
- Fertility tx
What is Down’s syndrome?
Three copies of chromosome 21 (trisomy 21)
Sx of Down’s syndrome?
- Hypotonia
- Brachycephaly (flat head)
- Short neck
- Short stature
- Flattened face and nose
- Prominent epicanthic folds (folds of skin covering medial portion of eye + eyelid)
- Single palmar crease
What are the antenatal screening tests for Down’s syndrome?
- Combined test:1st line - Performed between 11 and 14 wks gestation, USS measures nuchal translucency (thickness back of neck of fetus, in DS the thickness >6mm)
- Triple test:performed between 14 and 20 wks gestation, involves maternal blood test results therefore: higher Beta-HCG, lower Alpha-fetoprotein and lower serum oestriol indicate greater risk of Down’s syndrome.
- Quadruple test:Identical to triple test but also icnludes maternal blood for inhibin-A (higher inhibin-A = greater risk)
When the previous test results provide a risk score of > 1 in 150, then further tests are done to give a definitive answer, which are:
* Chorionic villus sampling (CVS)
* Amniocentesis
Mx of Down’s syndrome?
Supportive care from the MDT and follow up Ix such as:
* Regular thyroid checks (2 yearly)
* Echo to diagnose cardiac defects
* Regular audiometry for hearing impairment
* Regular eye checks
What is Fragile X syndrome?
Mutation in the FMR1 (fragile X mental retardation 1) gene on the X chromosome. The FMR1 gene codes for the fragile X mental retardation protein, which plays a role in cognitive development in the brain.
What kind of genetic inheritance is Fragile X syndrome?
X-linked (unclear if dominant or recessive)
Sx of Fragile X syndrome?
- Intellectual disability
- Long, narrow face + large ears
- Large testicles after puberty
- Hypermobile joints (particularly in the hands)
- ADHD
- Autism
- Seizures
Ix for Fragile X syndrome?
Genetic test that detects number of CGG repeats in FMR1 gene.
Mx of Fragile X syndrome?
MDT support + behavioural therapy
What is Angelman syndrome?
Loss of function of the UBE3A gene specifically copy inherited from mother.
This can be caused by:
* Deletion on chromosome 15
* Specific mutation in this gene
* If two copies of chromosome 15 are contributed by father w/no copy from mother
Sx of Angelman syndrome?
- Unusual fascination w/water
- Happy demeanour
- Widely spaced teeth
- Delayed development + learning disability
- Severe delay + absence of speech development
- Inappropriate laughter
- Hand flapping
What is Prader-Willi syndrome?
Loss of functional genes on the proximal arm of the chromosome 15 inherited from the father.
This can be due to:
* Deletion of this portion of chromosome
* When both copies of chromosome 15 are inherited from the mother.
Sx of Prader-Willi syndrome?
- Constant insatiable hunger (obesity)
- Hypotonia
- Mild-moderate learning disability
- Hypogonadism
- Fairer, soft skin that is prone to bruising
- Narrow forehead
- Downturned mouth
Mx of Prader-Willi syndrome?
- Growth hormone - improves muscle development + body compisition
- Dietician
What is Noonan syndrome?
An inherited autosomal dominant cdtn.
Sx of Noonan syndrome?
- Short stature
- Broad forehead
- Hypertelorism (wide space between eyes)
- Downward sloping eyes w/ptosis
- Low set ears
- Webbed neck
Associated cdtns to Noonan syndrome?
- Congenital heart disease
- Cryptorchidism (undescended testes)
- Learning disability
- Bleeding disorders
- Lymphoedema
What is William syndrome?
Deletion of genetic material on one copy of chromosome 7. It’s usually the result of a random deletion around conception.
Sx of Williams syndrome?
- Very sociable personality
- Starburst eyes (a star-like pattern on the iris)
- Wide mouth + widely spaced teeth
- Flattened nasal bridge
- Small chin
- Mild learning difficulty
Associated cdtns to Williams syndrome?
- Supravalvular aortic stenosis (narrowing just above aortic valve)
- ADHD
- HTN
- Hypercalcaemia
What is muscular dystrophy?
Genetic cdtns that cause gradual weakening + wasting of muscles.
What is Gower’s sign?
When children w/proximal muscle weak ess use a specific technique to stand up from a lying position - using their hands on their legs to help them stand up.
What is Duchennes Muscular Dystrophy?
Defective gene for dystrophin (a protein that helps hold muscles together at cellular level) on the X-chromosome.
What kind of genetic inheritance is Duchennes muscular dystrophy?
X-linked recessive
Tx of Duchennes muscular dystrophy?
- Oral steroids - slow progression of muscle weakness
- Creatine supplementation - improvement in muscle strength
What is Beckers muscular dystrophy?
Similar to Duchennes however dystrophin gene is less severely affected + maintains some of its function.
How does Beckers muscular dystrophy progress?
Sx only start to appear around 8-12 yrs. Some pts require a wheelchair in their late 20s/30s whereas others are able to walk with assistance into adulthood.
What is myotonic dystrophy?
- Progressive muscle weakness
- Prolonged muscle contractions
- Cataracts
- Cardiac arrhythmias
Example - pt is unable to let go after shaking someone’s hand or unable to release on doorknob after opening a door.
What is Patau syndrome?
aka trisomy 13. Genetic disorder in which person has extra copy of chromosome 13.
Sx of Patau syndrome?
- Microcephalic (small head), small eyes
- Cleft lip/palate
- Polydactyly
- Scalp lesions
What is Edwards syndrome?
aka Trisomy 18. Presence of an extra copy of chromosome 18 and leads to severe developmental + physical challenges.
Sx of Edward’s syndrome?
