Paeds - genetics Flashcards
(44 cards)
what are the appropriate situations for genetic testing?
in a child who has features of a genetic disorder
the child is asymptomatic but is at risk of a genetic condition for which preventative or other therapeutic measures are available
the child is at risk for a genetic condition with a paediatric onset for which preventive therapeutic measures are not available
what are inappropriate situations for genetic testing in a child?
an asymptomatic child is at risk for a genetic condition that usually has onset in adult life for which therapeutic measures are not available e.g. huntingtons
Testing for carrier status e.g. siblings of a child with CF
genetic testing of children for the benefit of another family member should not be performed unless testing is necessary to prevent substantial harm to the family member
what are the different types of chromosome testing?
Karyotype analysis
Fluorescence in situ hybridization (FISH)
Molecular kayotyping using microarrays
what is down’s syndrome?
Down’s syndrome (DS), or trisomy 21, is the most common genetic form of intellectual disability, occurring in 1 in 691 births. In addition to having characteristic physical features, short stature, and hypotonia, individuals with DS have a distinctive cognitive and behavioural profile. They also have a higher frequency of associated medical conditions, including congenital heart defects, and gastrointestinal, thyroid, haematological, audiological, and visual abnormalities.
what are the clinical features of Down’s Syndrome?
usually presents at birth
generalised hypotonia and marked head lag
facial features: small low set ears, up slanting eyes, prominent epicanthic folds, flat facial profile, protruding tongue
flat occiput
short neck
short broad hands, short incurved little fingers, single transverse palmer crease and a wide sandal gap between the first and second toes.
mildly short stature
hypotonia
intellectual impairment becomes apparent
what conditions are associated with Down syndrome?
40-50% will have congenital heart defects GI problems (duodenal atresia, Hirschsprung's disease, anal atresia) increased risk of infection developmental dysplasia of the hip eczema deafness cataracts leukaemia acquired hypothyroidism
what are the cardiac complications of Down’s Syndrome?
multiple cardiac problems may be present
endocardial cushion defect (most common, 40%, also known as atrioventricular septal canal defects)
ventricular septal defect (c. 30%)
secundum atrial septal defect (c. 10%)
tetralogy of Fallot (c. 5%)
isolated patent ductus arteriosus (c. 5%)
what are the complications of Down syndrome later in life?
subfertility: males are almost always infertile due to impaired spermatogenesis. Females are usually subfertile, and have an increased incidence of problems with pregnancy and labour learning difficulties short stature repeated respiratory infections (+hearing impairment from glue ear) acute lymphoblastic leukaemia hypothyroidism Alzheimer's disease atlantoaxial instability
What is the screening for down’s syndrome?
antenatal screening
- first trimester - the combined test is now standard: nuchal translucency measurement and serum B-HCG and pregnancy associated plasma protein A
- these tests should be done between 11-13 + 6 weeks
in the second trimester the patient is given the option to receive further diagnostic testing
either the triple (AFP, unconjugated oestriol, HCG) or the quadruple test (AFP, unconjugated oestraiol, HCG and inhibin A)
women have the option to have invasive diagnostic testing - amniocentesis.
what is Klinefelter’s syndrome?
It is associated with karyotype 47 XXY
an extra X chromosome - it leads to decreased testosterone production
what are the symptoms of Klinefelter’s syndrome?
Boys with Klinefelter syndrome enter puberty normally, but mid puberty the testes begin to involute and the boys develop hypergonadotropic hypogonadism with decreased testosterone production
they are often taller than average and may develop a feminine body build.
small firm testes in adult life generally infertile - azoospermia
gynaecomastia may develop (50%)
*often undiagnosed throughout childhood
often diagnosis only comes to light because of infertility
how is Klinefelter’s syndrome diagnosed?
diagnosis is by karyotype
what is turner’s syndrome?
it is a chromosomal disorder in females caused by either the presence of only one sex chromosome or a deletion of the short arm of one of the x chromosomes.
It is denoted as either 45XO or 45X
what are the features of turner’s syndrome?
- short stature
- shield chest, widely spaced nipples
- webbed neck
- bicuspid aortic valve, coarctation of the aorta
- primary amenorrhoea
- high-arched palate
- short fourth metacarpal
- delayed or absent pubertal development
- cystic hygroma which decreases with age but leaves them with neck webbing
- skeletal abnormalities
- horseshoe kidney - 2 kidneys become fused during development
what is the pathophysiology of turner’s syndrome?
only one complete X chromosome leads to increase rate of loss of eggs, they have menopause before menarche
this results in hypogonadism and decreased oestrogen.
how is turner’s syndrome managed?
if they have poor growth - give growth hormone - somatropin
how can turners syndrome be diagnosed antenatally?
Karyotype analysis either by chronic villus sampling or amniocentesis
if there is pubertal delay
give low dose oestrogen and cyclical progesterone can be added
what is Edwards syndrome?
trisomy 18
2nd most common trisomy following down’s syndrome
what are the symptoms of Edwards syndrome?
Micrognathia (underdeveloped jaw = small chin) Low-set ears Rocker bottom feet Overlapping of fingers cleft lip severe intellectual disability and failure to thrive congenital heart defects oesophageal atresia (polyhydramnios) kidney malformations increased risk of wilm's tumour
what are risk factors for Edwards syndrome?
increasing maternal age
family history
female babies
what is the prognosis of Edward’s syndrome?
most babies die before birth
if they are born they usually only survive for weeks to months
they usually die of central apnoea - the brain stops sending signals to the breathing muscle or due to severe cardiac abnormalities
how can Edwards syndrome be diagnosed antenatally?
USS - nuchal translucency, polyhydramnios
1st trimester - HCG and PAPP A are decreased compared to unaffected pregnancies
2nd trimester - AFP and uE3 also decrease, however inhibin A is typically normal
diagnosis can be confirmed with karyotyping
what is Patau syndrome?
trisomy 13
what are the clinical features of trisomy 13?
microcephaly holoprosencephaly meningomyelocele developmental delay gastrointestinal problems heart problems - septal defect polycystic kidney disease
cutis aplasia - scalp lesions
small eyes
polydactyly
rocker bottom feet
