Genetics and syndromes Flashcards by Alex Marsden

What is the genetic defect in Down’s syndrome?

trisomy 21

mostly translocation and mosaicism

How well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

What medical problems is down syndrome associated w ?

Hirschsprung’s disease
Duodenal atresia
CHD (VSD, PDA, AVSD)

How well did you know this?

Not at all

Perfectly

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 well did you know this?

Not at all

Perfectly

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

How well did you know this?

Not at all

Perfectly

What genetic abnormality is found in Patau syndrome?

Trisomy 13

How well did you know this?

Not at all

Perfectly

What are clinical features seen in Patau syndrome?

microcephaly
exomphalos
cleft lip/palate
polydactyly 
small eyes
scalp defects

How well did you know this?

Not at all

Perfectly

What is the prognosis of Patau syndrome?

almost all die by age 3

How well did you know this?

Not at all

Perfectly

What ,medical problems are associated w patau?

cardiac and renal

How well did you know this?

Not at all

Perfectly

What genetic abnormality is seen in Edward’s syndrome?

trisomy 18

How well did you know this?

Not at all

Perfectly

What gender is Edward’s syndrome more common in?

females

How well did you know this?

Not at all

Perfectly

What are some of the physical features of Edward’s syndrome?

micrognathia
low set ears
overlapping fingers
clubfoot (rocker bottom feet)

How well did you know this?

Not at all

Perfectly

What medical problems are associated w Edward’s syndrome?

severe LD

VSD

How well did you know this?

Not at all

Perfectly

What is the outlook for babies born with Edward’s syndrome?

most die by the first year

half by 2m

How well did you know this?

Not at all

Perfectly

what is the genetic abnormality seen in Prader-Willi syndrome?

lack of paternal 15q

How well did you know this?

Not at all

Perfectly

What are some of the clinical features seen in prader-willi syndrome?

obesity - can’t stop eating
hypogonadism
hypotonia
reduced IQ

How well did you know this?

Not at all

Perfectly

What is the genetic abnormality associated w Angelman syndrome?

lack of maternal 15q

How well did you know this?

Not at all

Perfectly

What are the clinical features of angelmans?

delayed development - severe LD
ataxic jerky movements
frequent laughter and smiling 
flapping hands
may not talk

How well did you know this?

Not at all

Perfectly

What is involved in the management of angelmans?

AEDs - valproate and clonazepam
scoliosis back brace or surgery
Orthoses
SALT

How well did you know this?

Not at all

Perfectly

What is the genetic abnormality found in fragile x syndrome?

X-linked

trinucleotide repeat expansion of CGG

How well did you know this?

Not at all

Perfectly

What are the physical features of fragile X syndrome?

large low set ears
long thin face
high arched palate
macroorchidism

How well did you know this?

Not at all

Perfectly

What gender if fragile X syndrome more common?

males

females mild-normal phenotype

How well did you know this?

Not at all

Perfectly

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?

1. Exercise to maintain muscle 2. Passive stretching and night splints (prevent contractors) 3. orthoses to prolong walking 4. Truncal brace, moulded sear, surgical rod for scoliosis 5. Overnight CPAP 6. Prednisolone slows decline in muscle strength

what is the median age of death of dMD>?

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