Genetics Flashcards

Question 1

Q

What can happens to chromosomes to bring about a chromosome disorder?

Answer

A

DELETION DUPLICATION TRANSLOCATION TRISOMY MOSAICISM (abnormal: structure, extra portion or extra number)

Question 2

Q

Example of a deletion chromosome disorder?

Answer

A

Portion of chromosome is missing.

Very rare.

“CRI DU CHAT” missing part of chromosome 5:

learning, developmental and speech and language difficulties
“cat like cry” as infants

Question 3

Q

Example of a duplication chromosome disorder?

Answer

A

CHARCOT-MARIE-TOOTH duplication of short arm of Chromosome 17:

sensory and motor neuropathy
characteristic “pes cavus” (high arching foot)

Portion of chromosome is duplicated, has twice the copies for some of the genes.

Question 4

Q

What is and examples of translocation chromosome disorder?

Answer

A

Portion of chromosome is switched into another (reciprocal or nonreciprocal).

No specific syndrome but increase risks other conditions (cancer, infertility etc):

PHILADELPHIA chromosome

Acute Myeloid Leukaemia. Reciprocal translocation, Chr 9 and Chr 22.

ROBERTSONIAN translocation in acrocentric (long arm) chromosomes 13, 14, 15, 21, 22. Short arm is lost so just two long arms, makes it look like one chromo is lost. Phenotypically normal but only 45 chromosomes when counted - risk for offspring.

Question 5

Q

Examples of trisomy chromosome disorders?

Answer

A

PATAU syndrome - trisomy 13

EDWARDS syndrome - trisomy 18

DOWNS syndrome - trisomy 21

Question 6

Q

What are the features of Patau and Edwards syndrome?

Answer

A

PATAU syndrome - trisomy 13:

microcephalic, holoprosencephaly
small eyes - cleft lip / palate
“rocker bottom feet” = convex soles
polydactyly
scalp lesions
cardiac defects, cystic kidneys

Question 7

Q

What are the features of Edward’s syndrome?

Answer

A

EDWARDS syndrome - trisomy 18:

micrognathia (small jaw), prom occiput
low-set ears
“rocker bottom feet” = convex soles
overlapping fingers, clenched hands
VSD, omphalocele, meckels diverticulum, horseshoe kidney, malrotation

Question 8

Q

What happens in mosaicism chromosome abnormality?

Answer

A

Happens after conception. Abnormality is in a portion of cells but not other. Each case is unique and unpredictable.

Question 9

Q

What diseases show mitochondrial inheritance?

Answer

A

Mitochondrial disease are myopathies and muscles have “red, ragged fibres”.

Heteroplasmy - poor genotype:phenotype correlation.

LEBER’S optic atrophy:

painless vision loss in adolescents

MELAS syndrome:

Mitochondrial Encephalomyopathy Lactic Acidosis and stroke-Like episodes

MERRF syndrome (encephalopathy not myopathy):

Myoclonus Epilepsy with Ragged-Red Fibres

KEARNS-SAYRE syndrome:

ophthalmoplegia
retinitis pigmentosa
onset <20yo
possible ptosis
heart block SENSORINEURAL hearing loss

Question 10

Q

What are the different ways of genetic testing?

Answer

A

KARYOTYPING

looking at number, size and shape of the chromosomes (Patau, Edwards, Downs)

MICROARRAY

enzymes cut up genes which then spread on plate according to weight, eg CF gene is heavier so you get a clump there

SPECIFIC GENE TESTING

split the DNA strands and then add a gene probe to look for a specific gene. DNA sequencing - only used in research, split strands and add nuceotides

Question 11

Q

Downs syndrome dysmorphic features and complications?

Answer

A

FEATURES:

hypotonia
brachycephaly (small head with flat back)
short neck, short stature
flat face and nose
prominent EPICANTHIC folds
upward sloping PALPEBRAL fissures
single PALMAR crease (simian crease)

COMPLICATIONS:

learning disability
dementia in adults
recurrent otitis media
deafness; Eustachian tube abnormal leads to glue ear and conductive hearing loss
visual; myopia, strabismus, cataracts
atlantoaxial instability
hypothyroidism
cardiac; ASD, VSD, PDA, tetralogy
duodenal atresia, Hirschsprungs
leukaemia (ALL)

Question 12

Q

There is screening and testing for Down’s, what are the screening tests?

Answer

A

COMBINED TEST 11-14 weeks US and blood, inc risk:

Nuchal translucency over 6mm
inc BETA-HCG
dec PAPPA (pregnancy associated plasma protein A)

TRIPLE TEST 14-20weeks, blood only, inc risk:

inc BETA-HCG
dec AFP dec SERUM OESTRIOL

QUADRUPLE TEST 14 -20 weeks, same as triple but with:

risk inc with INHIBIN-A Test give risk score, greater than 1 in 150 then offered testing (5% of pregnancies)

Question 13

Q

After screening what are the antenatal tests you can do for Down’s?

Answer

A

INVASIVE (foetal cells and karyotype them)

before 15 weeks: CHORIONIC VILLOUS SAMPLING (placental tissue)
beyond 15 weeks: AMNIOCENTESIS (amniotic fluid)

NON-INVASIVE prenatal testing

NIPT, DNA fragments in maternal blood

Question 14

Q

Management of Down’s?

Answer

A

OSCE q.

MDT:

OT
SALT
physio
dietician
paediatrician
GP
health visitors
cardiologist
ENT for ear
audiologist
optician
social services for care and benefits
educational support
charities such as Downs Syndrome Association

INVESTIGATIONS:

regular thyroid (2yrs)
echo for heart defects
regular audiometry
regular eye check

Average life-expectancy is 60 years

Question 15

Q

What are happens in Klinefelter syndrome? What are the features? Management and prognosis?

Answer

A

Male with additional X Chr, so 47 XXY or 48 XXXY.

Dx by karyotype (may see Barr body of extra chromo).

taller height, wide hips, long extremities
gynaecomastia
weak muscles
small testicles, reduced libido, infertile
shy, learning difficulties
low testosterone, low inhibin B, high LH and FSH, high oestrogen

MANAGEMENT:

testosterone injections
IVF for fertility
breast reduction surgery
MDT; SALT, OT, physio, education support

Almost normal life expectancy, some increased risk of breast cancer, osteoporosis, diabetes, anxiety and depression.

Question 16

Q

What happens in Turners syndrome? Features? Associated conditions and management?

Answer

Study These Flashcards

A

Female has just single X chr, so 45 X0.

short
webbed neck (cystic hygroma)
high arching palate
downward sloping eyes with ptosis
broad chest, wide nipples (shield chest)
cubitus valgus
underdeveloped ovaries (streak)
infertile
incomplete puberty
lymphoedema hands and feet
dec oestrogen, inc FSH and LH

ASSOCIATED:

recurrent otitis media and UTI
Ao coarc, bicuspid Ao valve
hypothyroid common
HTN
obesity, diabetes
osteoporosis
learning difficulty
ovary dysgerminoma

MANAGEMENT:

growth hormone therapy for short stature
oestrogen and progesterone for secondary sex characteristic and osteoporosis
fertility treatment
life expectancy almost normal.

Question 17

Q

What is Noonan syndrome? Features and associated conditions? Management?

Answer

Study These Flashcards

A

Majority are autosomal dominant on chromosome 12. Normal karyotype. (Features are like Turner’s but for both sexes)

short stature
broad forehead
webbed neck
wide nipples, chest carinatum / excavatum
down sloped eyes with wide space (hypertelorism)
low set ears
triangle shape face

ASSOCIATED:

pulmonary valve stenosis, ASD, hypertrophic cardiac myopathy
cryptorchidism and infertility in men
learning difficulty
bleeding disorder; factor XI deficiency
lymphoedema
increased risk leukaemia and neuroblastoma

MANAGEMENT:

supportive and MDT
heart disease; corrective surgery

Question 18

Q

What happens in Marfan’s syndrome and what are the features? Management?

Answer

Study These Flashcards

A

Autosomal dominant on chr 15 defect in FBN1 gene for FIBRILLIN in connective tissue.

tall, long neck, long limbs
dislocation and hypermobility
scoliosis of spine >20 degrees
arachnodactyly (long fingers)
pes planus
high arch palate
downward palpebral fissures
lens dislocation in eye
pectus carinatum / excavatum
pneumothorax
gastro oesophageal reflux
MITRAL VALVE PROLAPSE
AO VALVE PROLAPSE
ao anyurysms

OSCE tests for arachnodactyly:

thumb fold across palm and beyond (Steinberg sign) and fingers wrap around wrist (Walker-Murdoch sign)
murmurs of mitral or Ao regurg
palate, arm span, hypermobility (Beighton 5 score)

MANAGEMENT: