Genetics and syndromes Flashcards
What is the genetic defect in Down’s syndrome?
trisomy 21
mostly translocation and mosaicism
What are the clinical features of Down syndrome that can be seen at birth?
flat nasal bridge up slanting palpebral fissures low set small ears flat occiput protruding tongue single palmar crease sandal-toe deformity incurved 5th finger
What medical problems is down syndrome associated w ?
Hirschsprung’s disease
Duodenal atresia
CHD (VSD, PDA, AVSD)
What are medical signs found later in Down syndrome?
delayed milestones short stature low IQ Hearing impairment (secretory otitis media) visual: cataracts, squint, myopia Atlanta-axial instability risk of pneumonia ALL subfertility Alzheimers
How is Down syndrome diagnosed antenatally?
Combined test (11-13+6 weeks):
Nuchal translucency (thickened is associated w DS)
serum B-HCG
pregnancy associated plasma protein A (low indicates DS)
Then to confirm if higher risk:
• Chorionic villus sampling
• Amniocentesis
What genetic abnormality is found in Patau syndrome?
Trisomy 13
What are clinical features seen in Patau syndrome?
microcephaly exomphalos cleft lip/palate polydactyly small eyes scalp defects
What is the prognosis of Patau syndrome?
almost all die by age 3
What ,medical problems are associated w patau?
cardiac and renal
What genetic abnormality is seen in Edward’s syndrome?
trisomy 18
What gender is Edward’s syndrome more common in?
females
What are some of the physical features of Edward’s syndrome?
micrognathia
low set ears
overlapping fingers
clubfoot (rocker bottom feet)
What medical problems are associated w Edward’s syndrome?
severe LD
VSD
What is the outlook for babies born with Edward’s syndrome?
most die by the first year
half by 2m
what is the genetic abnormality seen in Prader-Willi syndrome?
lack of paternal 15q
What are some of the clinical features seen in prader-willi syndrome?
obesity - can’t stop eating
hypogonadism
hypotonia
reduced IQ
What is the genetic abnormality associated w Angelman syndrome?
lack of maternal 15q
What are the clinical features of angelmans?
delayed development - severe LD ataxic jerky movements frequent laughter and smiling flapping hands may not talk
What is involved in the management of angelmans?
AEDs - valproate and clonazepam
scoliosis back brace or surgery
Orthoses
SALT
What is the genetic abnormality found in fragile x syndrome?
X-linked
trinucleotide repeat expansion of CGG
What are the physical features of fragile X syndrome?
large low set ears
long thin face
high arched palate
macroorchidism
What gender if fragile X syndrome more common?
males
females mild-normal phenotype
How is a diagnosis of fragile X syndrome made antenatally?
chorionic villus sampling or amniocentesis
What are the signs of and medical associations of fragile x syndrome?
hypotonia (delayed motor milestones) autism is more common mitral valve prolapse learning difficulties behavioural problems
What is a possible treatment of fragile x syndrome? What is it indicated for?
minocycline for. general behaviour improvement
What is the genetic abnormality found in Klinefelter’s syndrome?
extra X chromosome in males
47 XXY
What re the clinical features of klinefelter’s syndrome?
clumsiness
LD
What are clinical features found in adults w klinefelters
tall
long limbs
gynaecomastia + infertility + hypogonadism + azoospermia
What are individuals w klinefelters at an increased risk of ?
increased risk of leg ulcers, osteoporosis and breast cancer
What is the treatment of klinefelter?
testosterone from puberty onwards to help development of secondary sexual characteristics and reduce long term risk of osteoporosis
What is the genetic abnormality found in Turner syndrome?
there is one X chromosome in the female
or a deletion of the short arm of one X chromosome
What are the features of Turner syndrome found in fetuses?
generalised oedema
nuchal thickening
what are some of the features found in neonates w turner syndrome?
peripheral oedema webbed neck short stature widely spaced nipples short 4th metacarpal
What are some of the late signs of Turner syndrome?
ovarian defects causing infertility hypothyroidism moles wide carrying angle of arm delayed puberty
What is the treatment of Turner syndrome?
growth hormone
oestrogen - development of secondary sexual characteristics
What is the genetic anomaly in Noonan syndrome?
autosomal dominant mutation
What are the cardiac problems associated w Turner syndrome?
bicuspid aortic valve
coarctation of aorta
What are the physical features of Noonan syndrome?
short stature
webbed neck
flat nose bridge
pacts excavatum
What are some of the medical problems associated w Noonan syndrome?
pulmonary valve stenosis
ASD
What is the genetic abnormality associated w William’s syndrome?
deletion of 26-28 genes on chromosome 7
What are the physical features of Williams syndrome?
short stature small upturned nose full lips small chin long philtrum puffy eyes
What are some of the medical conditions associated with Williams syndrome?
supravalvular aortic stenosis
mild mod LD
transient neonatal hypercalcaemia
What is muscular dystrophy?
group of inherited conditions w muscle degeneration often progressive
What is the most common muscular dystrophy?
Duchenne muscular dystrophy
What type of genetic disorder is DMD?
X linked recessive
Explain the pathophysiology behind DMD
mutations in dystrophin gene (Xp21.2)
loss of dystrophin so muscles get replaced by fibroadipose tissue
What age does DMD most commonly present?
1-6yrs
wHat is the typical presentation of DMD?
waddling gait
Gower’s manoeuvre - using hands to climb up legs
What abnormalities are found at birth in DMD?
none
what are late effects of DMD?
pseudohypertrophy of calves - unable to walk by 10-14 yrs
nocturnal hypoxia
resp impairment and infections
cardiomyopathy
orthopaedic - tendon contractures, scoliosis, osteoporosis
What are possible investigations for DMD?
increased serum creatinine kinase
muscle biopsy - abnormal fibres surrounded by fat and fibrosis tissue
Can also be diagnosed prenatally
What is the management of DMD?
- Exercise to maintain muscle
- Passive stretching and night splints (prevent contractors)
- orthoses to prolong walking
- Truncal brace, moulded sear, surgical rod for scoliosis
- Overnight CPAP
- Prednisolone slows decline in muscle strength
what is the median age of death of dMD>?
31
How does Beckers MD differ to Duchenne?
some functional dystrophin is produced so produces features like it but slower progression
what is the average age of onset of backers MD?
11yrs
What is LE of bEckers MD?
late forties to normal
