Genetics Flashcards
Klinefelter Syndrome
An additional X chromosome for men making them 47 XXY
Presentation of Klinefelter Syndrome
- Taller height - Wide hips - Gynaecomastia
- Weaker muscles
- Small testicles
- Reduced libido
- Shyness
- Infertility
- Subtle learning difficulties
Management of Klinefelter Syndrome
Testosterone injections - Advanced IVF techniques can potentially allow for IVF - Breast reduction surgery - MDT input to improve speech, language, strengthen muscles and provide education support.
Complications of Klinefelter Syndrome
There is an increased risk of breast cancer, osteoporosis, diabetes and anxiety
Turners Syndrome
Occurs when a female has a single X chromosome, making them 45 XO
Presentation of Turners Syndrome
- Short stature - Webbed neck - Widely spaced nipples with broad chest - High arching palate - Downward sloping with ptosis - Underdeveloped ovaries with reduced function - Late or incomplete puberty - Most women are infertile
Associated Conditions with Turners Syndrome
- Recurrent otitis media - Recurrent UTI - Hypothyroidism - Hypotension - Obesity - Diabetes
Management of Turners Syndrome
Growth hormone therapy can help with short stature - Oestrogen and progesterone replacement can help establish female sex characteristics, regulate menstrual cycle and prevent osteoporosis - Regular monitoring is needed for the associated conditions
Complications of Turners Syndrome
aortic problems, osteoporosis, autoimmune conditions, frequent otitis media, eye problems, horseshoe kidney, bicuspid aortic valve
Downs Syndrome
3 copies of chromosome 21
Presentation of Downs Syndrome
Hypotonia - Small head with flat back - Short neck - Short stature - Flattened face and nose - Low set ears - Single palmar crease - Prominent epicanthic folds (folds of skin covering the medial portion of the eye and eyelid) - Upward sloping palpebral fissures (gaps between the upper and lower eyelid)
Ix for Downs Syndrome
Antenatal Screening, Combined Test, Triple Test, Quadruple Test
Antenatal Screening for Downs Syndrome
This is offered to screen for chances of Down’s syndromes where further investigations will take place if necessary. Older mothers generally have a higher risk
Combined Test for Downs Syndrome
Performed at 11-14 weeks gestation and combines ultrasound results looking at thickness on the back of the neck of the foetus (thickened) and beta-HCG (raised) and PAPPA (reduced)
Triple Test for Downs Syndrome
Performed at 14-20 weeks and looks at beta-HCG (raised), AFP (low) and serum oestriol (low)
Quadruple Test for Downs Syndrome
- Same as triple test but also includes inhibin-A (high)
Management of Downs Syndrome
MDT approach involves every medical professional and regular screening of the complications include echo, regular thyroid checks, regular eye checks and audiometry
Complications of Downs Syndrome
- Learning disability - Recurrent otitis media - Deafness - Visual problems such as strabismus - Hypothyroidism - Cardiac defects such as ASD, VSD - Leukaemia - Dementia
Edwards Syndrome
Trisomy 18
Presentation of Edwards Syndrome
- Low birthweight - Small mouth and chin - Short sternum - Flexed, overlapping fingers - ‘Rocker-bottom feet’ - Cardiac and renal malformations
Complications of Edwards Syndrome
-90% have heart defect (PDA, ToF, CoA), developmental delays and severe learning disability, decreased muscle tone, decreased tone in airways
Prognosis of Edwards Syndrome
Most die before birth, some can live up to a year
3 types of Edwards Syndrome
Full , Partial, Mosaic
Patau Syndrome
Trisomy 13
3 Types of Patau Syndrome
Full , Partial, Mosaic
Median Survival of Patau Syndrome
~ 1 week
Presentation of Patau Syndrome
- Structural defects of the brain
- Scalp defects
- Small eyes and other eye defects
- Cleft lip and palate
- Polydactyly
- Cardiac and renal malformations
Fragile X Syndrome is caused by __
a mutation in the FMR1 gene on the X chromosome which codes for fragile X mental retardation protein which plays a role in cognitive development in the brain.
Inheritance of Fragile X Syndrome
X linked but unknown if dominant or recessive - Males are always affected and females vary in how they are affected due to the other X chromosome
Presentation of Fragile X Syndrome
Delay in speech and language development - Intellectual disability - Long, narrow face - Large ears - Large testicles after puberty - Hypermobile joints (particularly in the hands) - ADHD - Autism - Seizures
Management of Fragile X Syndrome
- Supportive for treating the symptoms and complications
Duchenne Muscular Dystrophy
Affecting around 1 in 4000 male infants, this is an inherited X linked recessive disorder resulting from a deletion on the short arm of the X chromosome.
Pathophysiology of Duchenne Muscular Dystrophy
This site codes for a protein called dystrophin which normally connects the cytoskeleton of muscle fibres to the extracellular matrix through the cell membrane therefore deficiency results in myofiber necrosis and raised serum CPK.
Presentation of Duchenne Muscular Dystrophy
- Waddling gait + slow at running + mount stairs one by one - Language delay - Gower’s sign - they need to turn prone to rise up from the floor - Pseudohypertrophy of the calves as the muscular tissue is replaced by fat/fibrous tissue - Boys will be slower and clumsier than their peers - They will no longer be able to walk by around 10-14 years due to the progressive muscular atrophy
Management of Duchenne Muscular Dystrophy
- Exercises to help maintain muscle power and mobility - Night splints and passive stretching - Good sitting posture helps reduce the likelihood of scoliosis - Corticosteroids can be given to help preserve mobility and prevent scoliosis
Becker Muscular Dystrophy
- Some functional dystrophin is produced therefore the features are similar as DMD however the disease progresses more slowly with age on onset being later.
Angelman Syndrome
Loss of function of the UBE3A gene on the copy inherited from the mother caused by a deletion on chromosome 15.
Presentation of Angelman Syndrome
Delayed development and learning disability - Severe delay or absence of speech development - Fascination with water - Happy demeanour - Widely spaced teeth - Inappropriate laughter - Abnormal sleep patterns - Epilepsy - ADHD - Dysmorphic features - Fair skin, light hair and blue eyes
Management of Angelman Syndrome
MDT approach to managing individual problems
Prader-Willi Syndrome
A genetic condition caused by loss of functional genes on the proximal arm of chromosome 15 inherited from the father which can be due to deletion of this portion or when both copies are inherited from the mother.
Presentation of Prader-Willi Syndrome
Constant insatiable hunger that leads to obesity - Hypotonia as an infant - Learning disability - Fairer, softer skin that is prone to bruising - Mental health problems such as anxiety - Dysmorphic features - Narrow forehead - Almond shaped eyes - Strabismus - Thin upper lip - Hypogonadism
Management of Prader-Willi Syndrome
No cure - Dietician management to control weight - Growth hormone is indicated by NICE to improve muscle development and body composition - Psychologists/Psychiatrists can help tackle mental health problems
Noonan Syndrome
A genetic condition which is mainly autosomal dominant
Presentation of Noonan Syndrome
Short stature - Broad forehead - Downward sloping eyes with ptosis - Wide space between the eyes - Low set ears - Webbed neck - Widely spaced nipples
Associated Conditions with Noonan Syndrome
Congenital heart disease, particularly pulmonary stenosis, hypertrophic cardiomyopathy and ADD - Undescended testes leading to infertility in males - Learning disability - Bleeding disorders - Increased risk of leukaemia
Management of Noonan Syndrome
- Supportive management with the MDT - Often corrective heart surgery is needed for the congenital heart disease
William Syndrome
Deletion of epigenetic material on one copy of chromosome 7 resulting in just a single copy of the genes - usually due to a random deletion during conception.
Presentation of William Syndrome
Broad forehead - Starburst eyes (star like pattern on the iris) - Flattened nasal bridge - Very sociable, trusting personality - Wide mouth with widely spaced teeth - Small chin
Management of William Syndrome
MDT approach to managing individual problems
Complications of William Syndrome
Supravalvular aortic stenosis - ADHD - Hypertension - Hypercalcaemia
