Paediatric Genetics Flashcards
What are the genetics of fragile x?
Expansion of the trinucleotide repeat CGG in the FMRI gene on the X chromosome
How many cgg repeats cause fragile x
Over 200
How does fragile x present?
Long face, protruding ears, intellectual impairment, post pubertal macroorchidism, social anxiety, features of autism
what cardiac condition is most associated with turners
a bicuspid aortic valve
What murmur is commonly heard in turners syndrome and why?
a cescendo -decrescendo ejection systolic murmur
due to bicuspid aortic valve
What is the most serious long term health condition associated with Turner’s syndrome
aortic dissection
How does williams syndrome present?
very friendly social affect
elfin-like facies
learning difficulties,
short stature
transient neonatal hypercalcaemia
supravalvular aortic stenosis
what genetic abnormality causes william’s syndrome?
microdeletion on chromosome 7
In a child with haemophilia which relative is most likely to have it?
maternal uncle, maternal grandfather etc- boys get their X chromosome from their mother so will need to be from the maternal side
What is the inheritance of prader-willi?
imprinting
If a female has haemophilia, what genetic condition might they have and why?
Turner’s
Haemophilia is x linked recessive- Turner’s only have one x chromosome so may develop x linked conditions
what chromosome is most commonly affected in patau syndrome
13
Presentation of prader - willi sydrome
hypotonia during infancy
poor suck
weak cry
dysmorphic features
short stature
hypogonadism
learning difficulties
childhood obesity
genetics of prader willi
microdeletion of paternal 15q11-13
is prader willi inherited from father or mother
father
genetics of fragile X
expansion of the CGG trinucleotide repeate on the FMRI gene on the X chromosome
Is fragile X transmitted from the mother or father ?
almost always mother as X chromosome
How does fragile X present?
long face
protruding ears
intellectual impairment
post-pubertal macroorchidism
social anxiety
ASD features
Genetics of turners syndrome
loss or abnormality of the second X chromosome in girls
Denoted 45 X
How does turners syndrome present
short stature,
amenorrhoea (ovarian dysgenesis),
widely spaced nipples
neck webbing
delayed puberty
lymphoedema of hands and feet in neonate
hypothyroidism
what congenital cardiac abnormalities may be present in turner’s syndrome
bicuspid aortic valve and coarctation of the aorta
What cardiac conditions can cause long term health problems for those with turners syndrome
aortic dilation and dissection
what renal condition may be associated with turner’s syndrome
horseshoe kidney
what endocrine condition is increased in turners syndrome
hypothyroidism
Genetics of angelman syndrome
loss of the maternal UBE3A gene caused by a deletion on chromosome 15
How does Angelman syndrome present
happy demanour
fascination with water
delayed development and learning disability
widely spaced teeth
coordination and balance problems
epilepsy
What are the genetics of williams syndrome?
microdeletion on chromosome 7
how does williams syndrome present?
elfin-like facial features
very friendly affect
starburst eyes
flatterned nasal bridge
wide mouth and widely space teeth
learning difficulties
what are 2 associated conditions with williams syndrome
transient neonatal hypercalcaemia
supravalvular aortic stenosis
how is williams syndrome diagnosed
fish studies
Genetics of noonan syndrome
autosomal dominant condition- defect on chromosome 12
How does noonan syndrome present
similar to turners :
- webbed neck
- widely spaced nipples
- short stature
- pectus carinatum and excavatum
Other features:
- pulmonary valve stenosis (newborn with have a murmur)
- ptosis
-crytorchidism
- delayed puberty
- factor XI deficiency
diagnosis of noonan syndrome
Genetic testing
Echo
Coagulation profile
Genetics of DiGeorge syndrome
deletion in chromosome 22
What is another name for digeorge syndrome
velocardiofacial syndrome
Triad of DiGeorge syndrome
cardiac abnormalities
hypoplastic thymus
hypocalcaemia (due to parathyroid hypoplasia)
Why do you get immunodeficiency in DiGeorge’s syndrome ?
as there is hypoplasia of the thymus leading to a lack of T cells.
Presentation of DiGeorge’s syndrome
cardiac abnormalities- murmur, HF
cleft lip and palate
immunodeficiency
cognitive impairment
growth failure
schizophrenia
hypocalcaemia- seizures, tetany
How is digeorge’s syndrome diagnosed?
Genetic karyotyping
Serum calcium and PTH
T cell count
Echo
Pathophysiology of DiGeorge’s syndrome
disruption of the development of the pharyngeal arches and pouches
Genetics of patau syndrome
trisomy 13
presentation of patau syndrome
microcephaly
small eyes
cleft lip and palate
polydactyl
scalp lesions
cardiac and renal malformations
What are muscular dystrophies?
genetic diseases characterised by progressive degeneration and weakness of specific muscle groups
inheritance of duchenne’s muscular dystrophy
x linked recessive
genetics of duchenne muscular dystrophy
a mutation in the dystrophin gene on the x chromosome
What is Becker’s muscular dystrophy
a milder form of duchenne’s muscular dystrophy, less effective dystrophin gene but sme function maintained
characteristic feature of myotonic muscular dystrophy
patient is unable to let go of a hand after shaking it
what muscular dystrophy is associated with a child sleeping with their eyes slightly open and weakness in pursing lips
fascioscapulohumeral muscular dystrophy
pathophysiology of duchenne muscular dystrophy
absence of dystrophin which is a cytoskeletal protein that provides structural stability to the dystroglycan complex in cell membranes
Causes necrosis of the muscle fibres and replacement of them with adipose and connective tissue.
Muscles become weaker and unusually firm
Presentation of duchenne’s muscular dystrophy
usually presents around the age of 4 with clumsy walking, difficulty standing and resp failure
- imbalance of lower limb strength
- delayed motor milestones
- unusually firm muscles
- diminished muscle tone
- pseudohypertrophy
- normal sensation
- urinary or bowel incontinence
- mild to severe intellectual impairment
What sign is common in duchenne’s muscular dystrophy
Gower’s sign- patient climbs up his body to stand from seated position
how is duchenne’s muscular dystrophy diagnosed?
serum creatinine kinase increased
genetic testing
EMG
muscle biopsy
first line investigation for duchenne muscular dystrophy
creatinine kinase
gold standard investigation of duchenne muscular dystrophy
genetic testing
What are the genetics of Klinefelter’s syndrome?
47XXY- it is a sex chromosome disorder where a male has an additional X chromosome
When does Klinefelter’s often get diagnosed
in early adulthood- 20s to 30s as male infertility
How common is Klinefelter’s syndrome?
1 in 660 men
What type of infertility does Klinefelter’s cause?
hypergonadotrophic hypogonadism- there will be high LH and FSH and low testosterone
What dose the additional X chromosome in Klinefelter’s syndrome do?
leads to hypoperfusion of the testes and testicular deficiency
Presentation of Klinefelter’s syndrome
small firm testes
decreased facial and pubic hair
loss of libido
impotence
infertility
tall, slender with long narrow shoulders and wide hips
gynaecomastia
delayed speech development
How is Kilnefelter’s syndrome diagnosed?
karyotyping
total serum testosterone- low
serum LH and FSH- raised
How is Klinefelter’s syndrome treated ?
testosterone therapy and fertility counselling
What complications are associated with Klinefelter’s asside from infertility
diabetes, osteoporosis, CVD, breast cancer
Genetics of downs syndrome
trisomy 21
How does downs syndrome present?
hypotonia
short neck
short stature
flattened face and nose
prominent epicanthic folds
upward sloping palpebral fissures
single palmar crease
Brushfeild spots on the iris
developmental delay and learning difficulty
What different antenatal screening tests can be used to screen for Downs
Combined test
Triple test
Quadruple test
When can the combined test be done?
between 11 and 14 weeks gestation
What are the three components of the combined test
- nuchel transluceny thickness
- beta- HCG
- PAPPA (pregnancy associated protein A)
what findings of the combined test suggest Downs syndrome
increased nuchel tranlucency thickness
increased beta HCG
low PAPPA
When can the triple test be done to screen for Downs
between 14-20 weeks
What are the components of the triple test?
three blood results:
- beta-HCG
- Alpha-fetaprotein (AFP)
- serum oestriol
what results on the triple test suggest downs syndrome
high beta HCG
low AFP
low oestriol
When can the quadruple test be done
between 14-20 weeks
What are the components of the quadruple test
beta-HCG (raised)
AFP (low)
Oestriol (low)
Inhibin A (high)
If screening tests suggest increased risk of Downs syndrome what further antenatal test can be done
Amniocentesis
Chorionic villus sampling
Non-invasive prenatal testing (NIPT)
When can chorionic villus sampling be used?
before 15 weeks
What are some complications of Downs syndrome
cardiac defects- AV septal defect, Ventricular septal defect and ASD
Recurrent otitis emdia
Deafness
Atlantoaxial instability
Leukaemia
Respiratory problems (obstructive sleep apnoea)
What cardiac abnormalities are associated with Downs syndrome and which is most common
AV septal defect (most common)
Ventricular septal defect
Atrial septal defect
What follow up tests should patients with downs syndrome receive
echo
regular audiometry
regular eye checks
2 yearly thyroid checks
Inheritance of cystic fibrosis
autosomal recessive
What is the genetic defect in cystic fibrosis?
Mutation in the CFTR gene found on chromosome 7
Pathophysiology of cystic fibrosis
The is a mutation in the CFTR anion channel which results in abnormal chloride and sodium transport and thick sticky secretions
How might cystic fibrosis present in newborns?
failure to pass meconium (meconium ileus)
How can cystic fibrosis present in infancy
prolonged neonatal jaundice
faltering growth
recurrent chest infections
steatorrhea
How can cystic fibrosis present in young children
bronchiectasis
rectal prolapse
nasal polyps
sinusitis.
Symptoms of cystic fibrosis (general)
Chronic cough and thick sputum production
steatorrhoea- due to lack of fat digesting lipases
faltering growth
Fasal polyps
recurrent respiratory infections
diabetes mellitus
jaundice
clubbing
How is cystic fibrosis usually diagnosed ?
on the newborn heelprick test- immunoreactive trypsinogen test
What test is used to diagnosed cystic fibrosis beyond neonates
sweat test- pilocarpine used to produce sweat and then the sweat is tested showing chloride more than 60
What bacteria can colonise those with cystic fibrosis
staph aureus
haemophilus influenzae
klebsiella
e.coli
pseudomonas aeruginosa
Why may men with cystic fibrosis suffer infertility
absent vas deferens
Gold standard diagnosis of duchenne’s muscular dystrophy
genetic testing (now easier than muscle biopsy)
