Genetics & Syndromes

Question 1

what is the inheritance pattern of Duchenne Muscular Dystrophy?

Answer 1

X linked recessive therefore it is much more common in males because if they inherit the defective copy from mum they will definitely get the condition. Girl will only develop if mum is a carrier (and girl gets this copy) + dad is affected. but 1/3 of affected pts are de novo mutations.

Question 2

what are the clinical features of Duchenne Muscular Dystrophy?

Answer 2

• pseudohypertrophy of the calves due to replace of muscles with fibrous + fat tissue.
• gower’s sign - must turn prone to get up from sitting due to relatively weak hip extensors, knee extensors, ankle dorsiflexors.
  Deep tendon reflexes diminshed + hypotonia in all muscle groups, sensation normal.
  mildly delayed motor development (av age begin ambulate 18months)
  waddling gait, unsteady
  mount stairs one by one, run slowly
  proximal hip girdle weakness
  slower and clumsier than peers
  by 10-14 they are no longer ambulatory
  1/3 have LD / ADHD.
  walk on toes + increased lumbar lordosis to keep centre of gravity behind hips + in front knees.
  scoliosis + urinary/ bowel incontinence not uncommon

Question 3

how is Duchenne Muscular Dystrophy screened for?

Answer 3

elevated Creatine Kinase (50-100x normal levels) due to myofibril necrosis but these do not necessarily become super high until 1 year of age.
Genetic testing. If both negative, electromyography + muscle biopsy might be required.

Question 4

What is the management of Duchenne Muscular Dystrophy?

Answer 4

1. Glucocorticoids to preserve muscle strength + delay loss of ambulation
2. physical therapy.
3. ADD TO

Question 5

what are the clinical features of Down’s Syndrome?

Answer 5

FAce: brachycephaly aka flat occiput (flat back of head instead of curved), upslanting palpebrae fissures, epicanthic folds, protruding tongue, brush field spots on the iris, flat nasal bridge, small nasal flares, low set small ears
NECK: short, extra skin (nuchal thickness)
HEART: AVSD pathognomonic, VSD (most common CHD in DS)
Others: Hypotonia, duodenal atresia, Hirschsprung’s
HANDS: single palmar crease, inward slanting fifth finger
FEET: wide space between big toe + second toe

Question 6

what are the cytogenetics and obs RF for Down syndrome?

Answer 6

3 main possibilities for cytogenetics: most common is meiotic non-dysjunction, translocation, mosaicism.
meiotic non-dysjunction: where pair of Chr 21 fail to divide to each go to one gamete, so both end up in one gamete and one gamete has none. This is related usually to maternal age but bc more under 35 have kids most affected babies born to young mums.
translocation: parent is carrier of translocation (but normal pheno) where chr 21 is ‘joined’ to 14 and then there is a chance that the other chr 21 is duplicated therefore have 2 copies of 21 + copy joined to chr 14. can also happen if parent has DS. If carrier, increased risk of DS recurrence.
mosaicism (rare): some cells normal some have trisomy 21,
RF: increased maternal age, sibling with DS, parental karyotype with translocation.

Question 7

what are the long term complications of Down syndrome?

Answer 7

HEART: CHD (VSD/ AVSD)
BRAIN: delayed motor development, LD, Epilepsy, Alzheimer’s, Atlanto-axial instability
SENSES: hearing impairment due to secretory OM, visual impariment- squint, cataracts, myopia
small stature
SYSTEMIC: increased risk leukaemia + solid tumours, infections, hypothyroid, coeliac
GI: feeding difficulty due to hypotonia, diff coordinating sucking, constipation.

Question 8

what are the diagnostic investigations for Down syndrome?

Answer 8

chromosomal analysis
Nuchal thickness- antenatal scan
amniocentesis karyotyping baby