Genetic conditions Flashcards
Features of tetralogy of fallot
ventricular septal defect (VSD)
right ventricular hypertrophy
right ventricular outflow tract obstruction, pulmonary stenosis
overriding aorta
What is the most common cause of cyanotic heart disease in infants
Tetralogy of Fallot
- typically presents at around 1-2 months (may not until 6 months old
What is the management of tetralogy of fallot
Surgical repair is often undertaken in two parts
cyanotic episodes may be helped by beta-blockers to reduce infundibular spasm
Clinical features of down syndrome
face: upslanting palpebral fissures, epicanthic folds, Brushfield spots in iris, protruding tongue, small low-set ears, round/flat face
flat occiput
single palmar crease, pronounced ‘sandal gap’ between big and first toe
hypotonia
congenital heart defects (40-50%, see below)
duodenal atresia
Hirschsprung’s disease
Cardiac complications in down 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%)
Non cardiac complications in down syndrome
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 causes trisomy 21
3 copies pf chromosome 21
What is the genetic mechanism
maternal meiotic non-disjunction (95%)
What immediate health concerns must you rule out with down syndrome
cardiac anomalies - avsd
Bowel obstruction - duodenal atresia/hirshsprungs
How do you diagnose trisomy 21
rapid aneuploidy screen - once this confirms down syndrome, you would carry out karyotyping
Key features of down syndrome in neonates
hypotonism sleepy - difficult to wake for feeds epicanthic folds small ears protruding tongue excess nuchal skin hypo-pigmented iris pseudo strabisus (caused by epicanthic folds)
What is the most common cardiac anomaly in down syndrome
atrial ventricular septal defect
other septal and valvular defects are common
40% of down syndrome babies have a cardiac anomaly
What other features may be picked up on screening that are associated with trisomy 21
conductive and sensorineural hearing defects
hypothyroidism
which markers prenataly may indicate down syndrome
AFP - lower
unconjugated oestriol - lower
Inhibin A
human chorionic gonadotrophin - higher
which chromosomes does rapid aneuploidy screen (RAS) look at?
13, 18, 21 and sex
What does trisomy 13 (Patau) cause
- Holoprosencephaly - no hemispheres in brain
- orofacial clefts
- polydactyl
What does Edward syndrome (18) cause
- prenatal growth deficiency
- over-riding fingers
- congenital heart disease
What is a robertsonian translocation
2 chromosomes lose their short arms and the long arms join together
What is mosiacism
effected gene not present in every ceel in the body
What is a point mutation
A base pair is altered. Can either be:
- silent mutation - same amino acid
- Missence - altered codon corresponds to a different amino acid
- nonsense- altered codon corresponds to a stop signal
What is fragile X
Mutation which prevents the development of fragile X mental retardation protein.
It affects both male and females but males tend to have more severe features
What are the features of fragile x
intelectual disability
delayed motor ability
behavioural problems
toe walking
What type of genetic condition is fragile X
X linked dominant CCG trinucleotide repeat
What are 2 adult osnet disorsders associated with fragile X
- fragile X tremor-ataxia syndrome (FXTAS)
- primary ovarian insufficiency (POI
What physical features may be assoc. with fragile X
- Large head, long face, prominent forehead and chin
- protruding ears
- loose joints
- large teste
these are variable and may not present until puberty
What is Turners syndrome
partial or complete loss (monosomy) of one of the second sex chromosomes - 45X!
only affects female
What are the key features of Turner
short stature (<5ft) ovarian failure short webbed neck Can have intelectual difficulties but not always lymphoedema bicuspid aortic valve coarctation of the aorta (5-10%)
What is Kleinfelters syndrome
Boy are born with an extra X chromosome - nondisconjunction (random)
Key features of Kleinfelter
- primary hypogonadism
- small, firm testicles
- delayed/incompelte puberty
- breast growth
- small stature
- infertility
When do you use chromosomal micro array analysis (CGH)
When there is no specific congenital disorder
What is fluorescent in situ hybridisation
assesses specific DNA sequences so is only used when a specific disorder is suspected eg. 22q11
What is the screening test for neuroblastoma
urinary HVA and VMA
What is associated with Beckwidth weidman syndrome
Ophacele Wilms tumour hypoglycaemia left sided hemi-hypertrophy large protruding tongue
What is the surveillance for Beckwidth Weidman syndrome
Abdo US every 3 months until 7
What screening do you do for Wilms tumour
urinary calcium/cr ratio every 6 months until 4 years
What x ray findings would suggest dueodenal atresia
double bubble with no distal gas
Features of angelmans syndrome
intelectual impairment microcephaly seizures jerky limb movement generally happy demeanour
What is the chromosomal abnormality in angelmans syndrome
micro deletion at 15q11.2-q13
What is the chromosomal abnormality in Retts syndrome
MECP2
What are the features of Retts syndrome
intellectual impairment seizures hand movements (repititive/purposeless) marked impairment of non-verbal communication screaming fitts/inconsolable crying
Features of smith-lemil-optiz syndrome
microcephaly
learning difficulties
abnormalities of digits
What is the chromosomal abnormality in smith-lemil-optiz syndrome
DHCR7
