Paeds: Genetics Flashcards
what is Down’s Syndrome caused by?
trisomy 21
what are the dysmorphic features of Down’s syndrome? (8)
- hypotonia
- Brachycephaly (small head with a flat back)
- short neck
- short stature
- flattened face + nose
- prominent epicanthic folds
- upwards sloping palpable fissures
- single palmar crease
complications of Down’s syndrome (9)
- learning disability
- recurrent otitis media
- deafness: eustachian tube abnormalities –> glue ear + conductive hearing loss
- visual problems: myopia, strabismus + cataracts
- hypothyroidism
- cardiac defects: ASD, VSD, PDA, ToF
- atlantoaxial instability
- leukaemia more common
- dementia more common
3 antenatal screening tests for Down’s screening
- 1st line: Combined test
- Triple test
- Quadruple test
what is the combined test?
performed between 11-14w gestation
US + beta-HCG + PAPPA
US: Down’s if nuchal thickness >6mm
beta-HCG: higher result indicates a greater risk
Pregnancy-associated plasma protein-A: lower result indicates a greater risk
what is the triple test
performed between 14-20w gestation
Beta-HCG: higher result indicates a greater risk
Alpha-fetoprotein: lower result indicates a greater risk
Serum oestriol: lower result indicates a greater risk
what is the quadruple test?
performed between 14-20w gestation
Beta-HCG + AFP + serum oestriol + inhibin-A
inhibin-A: higher result indicates a greater risk
what is offered if the risk score for the fetus having Down’s syndrome is > 1 in 150
the woman is offered amniocentesis or chorionic villus sampling
this involves taking a sample of the fetal cells –> karyotyping
what does chorionic villus sampling involve?
an US guided biopsy of the placental tissue
done before 15w
what does amniocentesis involve?
US guided aspiration of some amniotic fluid using a needle + syringe
this is done after 15w once there is enough amniotic fluid to make it safer to take a sample
what is non-invasive prenatal testing (NIPT)?
gradually being rolled out in the NHS. Not definitive test but gives good indication of whether fetus is affected.
blood test from mother. DNA fragments analysed, some of which will come from the placental tissue and represent the fetal DNA
Mnx of Down’s
involve members of the MDT:
- occupational therapy
- speech + language
- physio
- dietician
- paediatrician
- GP
- health visitors
- cardiologist
- ENT
- audiologist
- optician
- social services
- additional support w/ education needs
- charity: Down’s Syndrome Association
name 4 routine follow up investigations that are important for children with Down’s syndrome
1) 2-yearly thyroid checks
2) echocardiogram: cardiac defects
3) audiometry
4) eye checks
what is the average life expectancy for someone with Down’s syndrome
60 years
what is Klinefelter syndrome
occurs when a male has an additional X chromosome making them 47 XXY
features of Klinefelter syndrome
males appear normal until puberty:
- taller height
- wider hips
- gynaecomastia
- weaker muscles
- small testicles
- reduced libido
- shyness
- infertility
- subtle learning difficulties (esp affecting speech + language)
mnx options for Klinefelter syndrome
- testosterone injections
- advanced IVF techniques: have the potential to allow fertility
- breast reduction surgery
MDT:
- speech + language therapy
- occupational therapy
- physiotherapy
- educational support
In Klinefelter syndrome there is a slight increased risk of? (4)
- breast cancer compared with other males
- osteoporosis
- diabetes
- anxiety + depression
What is Turner’s syndrome?
when a female has a single X chromosome making them 45XO
what are the 3 classic features in Turner’s syndrome?
- short stature
- webbed neck
- widely spaced nipples
name the features of Turner’s syndrome? (9)
- short stature
- webbed neck
- widely spaced nipples
- high arching palate
- downward sloping eyes w/ ptosis
- cubitus valgus
- underdeveloped ovaries w/ reduced function
- late or incomplete puberty
- most women are infertile
Turner’s syndrome
what is cubitus valgus
abnormal feature of the elbow
when the arm is extended downwards with the palms facing forward
the angle of the forearm at the elbow is exaggerated, angled away from the body
Turner’s syndrome
associated conditions (9)
- recurrent otitis media
- recurrent UTIs
- coarctation of the aorta
- hypothyroidism
- hypertension
- obesity
- diabetes
- osteoporosis
- various specific learning disabilities
Turner’s syndrome
management
- GH: to prevent short stature
- oestrogen + progesterone replacement: can help establish female secondary sex characteristics, regulate the menstrual cycle + prevent osteoporosis
- fertility trx: can increase chances of becoming pregnant
Noonan Syndrome
inheritance pattern
autosomal dominant
Noonan Syndrome
features (8)
- short stature
- broad forehead
- downward sloping eyes w/ ptosis
- Hypertelorism: wide space between the eyes
- prominent nasolabial folds
- low set ears
- webbed neck
- widely spaced nipples
Noonan Syndrome
Associated conditions (6)
- congenital heart disease (pulmonary valve stenosis, hypertrophic cardiomyopathy, ASD)
- Cryptorchidism (undescended testes) –> infertility. Fertility normal in women
- learning disability
- bleeding disorders
- lymphoedema
- increased risk of leukaemia + neuroblastoma
Noonan Syndrome
Management
supportive w/ MDT
the main complication is congenital heart disease and patients will require corrective heart surgery
Marfan Syndrome
inheritance pattern
autosomal dominant condition affecting the gene responsible for creating fibrillin
Marfan Syndrome
what is fibrillin?
an important component of connective tissue resulting in features of abnormal connective tissue
Marfan Syndrome
features (8)
- tall stature
- long neck
- long limbs
- arachnodactyly: long fingers
- high arch palate
- hypermobility
- pectus carinatum or pectus excavatum
- downward sloping palpable fissures
Marfan Syndrome
test for arachnodactyly (long fingers)
- if thumb tip can go past opposite edge of hand
2. if finger and thumb overlap when wrapped around other wrist
Marfan Syndrome
associated conditions (7)
- mitral or aortic regurgitation
- lens dislocation in the eye
- joint dislocations
- scoliosis of spine
- pneumothorax
- GOR
- aortic aneurysms
Marfan Syndrome
management
- surgical correction of cardiac complications
Aim: minimise BP + HR to minimise stress on the heart
- lifestyle changes: avoid intense exercise + avoid caffeine
- BB + angiotensin II receptor antagonists
- carefully consider pregnancy as risk of aortic aneurysms
physio: strengthen joints + reduce symptoms arising from hypermobility
genetic counselling
monitor with yearly echo and ophthalmologist
Fragile X Syndrome
cause
mutation in the FMR1 gene (fragile x mental retardation)
on the X chromosome
trinucleotide repeat disorder
Fragile X Syndrome
what does the FMR1 gene code for?
the fragile X mental retardation protein
which plays a role in cognitive development in the brain
Fragile X Syndrome
inheritance pattern
X-linked but unclear whether it is dominant or recessive
Fragile X Syndrome
are males or females affected?
males are always affected
females can vary in how much they are affected
Fragile X Syndrome
mother is phenotypically normal. 2 ways in which the child may have got Fragile X Syndrome
- child inherited the X chromosome from their mother
2. de novo (random) mutation
Fragile X Syndrome
features (9)
- delay in speech + language development
- intellectual disability
- long, narrow face,
- large ears
- large testicles after puberty
- hypermobile joints (esp in hands)
- ADHD
- Autism
- Seizures
Fragile X Syndrome
mnx
supportive:
- MDT to support the learning disability, manage autism + ADHD + treat seizures if they occur
Fragile X Syndrome
life expectancy
similar to general population depending on associated disabilities + complications
Prader-Willi Syndrome
cause
loss of functional genes on the proximal arm of Ch15
inherited from father
can be due to a deletion of this portion of the Ch or when both copies of Ch15 are inherited from the mother
Prader-Willi Syndrome
key feature
constant insatiable hunger that leads to obesity
Katie Price’s son, Harvey
Prader-Willi Syndrome
features (12)
- constant insatiable hunger –> obesity
- hypotonia as an infant
- mild-moderate learning disability
- hypogonadism
- fairer, soft skin prone to bruising
- mental health problems (esp anxiety)
- dysmorphic features
- narrow forehead
- almond shaped eyes
- strabismus
- thin upper lip
- downturned mouth
Prader-Willi Syndrome
mnx
- GH: improve muscle development + body composition
- limit access to food by locking it
- dieticians
- education support, social workers, psychologists, physios, occupational therapists
Angelman Syndrome
cause
loss of function of the UBE3A gene, specifically the copy of the gene that is inherited from the mother
caused by a deletion on Ch15, a specific mutation in this gene or where 2 copies of Ch15 are contributed by the father, with no copy from the mother
Angelman Syndrome
3 key features
- WIDELY SPACED TEETH
- UNUSUAL FASCINATION W/ WATER
- HAPPY DEMEANOUR
Angelman Syndrome
other features (14)
- delayed development + learning disability
- severe delay or absence of speech development
- ataxia
- inappropriate laughter
- hand flapping
- abnormal sleep patterns
- epilepsy
- ADHD
- dysmorphic features
- microcephaly
- fair skin, light hair + blue eyes
- wide mouth with widely spaced teeth
Angelman Syndrome
Mnx
MDT:
- parental education
- social services + support
- educational support
- physio
- occupational therapy
- psychology
- CAMHS
- anti-epileptic medication where required
difference between Prader Willi and Angelman syndrome
Prader WIlli is inherited from dad
Angelman is inherited from mother
William Syndrome
cause
deletion of genetic material on one copy of Ch7
usually result of a random deletion around conception, rather than being inherited from an affected parent
William Syndrome
3 key features
- starburst eyes
- very sociable trusting personality
- wide mouth with a big smile
William Syndrome
features
- broad forehead
- starburst eyes
- flattened nasal bridge
- long philtrum
- wide mouth w/ widely spaced teeth
- small chin
- v.sociable trusting personality
- mild learning disability
William Syndrome
associated conditions
- supravalvular aortic stenosis
- hypercalcaemia
- ADHD
- HTN
William Syndrome
mnx
MDT
echo and BP monitoring to assess for aortic stenosis + HTN
low Ca diet may be required to control hypercalcaemia
which conditions is oesophagheal atresia more common in
trisomies – Downs/Pataus/Edwards
why does oesophagheal atresia present with polyhydramnios
As the oesophagus is blind-ending, fluid cannot pass through the baby to be absorbed. This results in an accumulation of fluid outside the baby
presentation of oesophagheal atresia
problems with swallowing. The baby will have difficulty feeding and has overflow saliva.
