Genetic disorder.txt

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  1. What is the incidence of Downs?
    1 in 650
  2. What are the features of Downs at birth?
    • Hypotonia
    • Flat occiput
    • Single palmar crease
    • Sandal gap between toes
    • Downward slanting eyes
    • Epicanthic folds
  3. What is the age related risk for Downs? 20yr, 30yr, 35yr, 40yr, 45
    • 20: 1 in 1500
    • 30: 1 in 1000
    • 35: 1 in 350
    • 40: 1 in 100
    • 45: 1 in 30
  4. How is Downs confirmed?
    • FISH DNA analysis
    • Must tell parents
  5. Why is it difficult to give precise long term implications of DS to parents?
    Variation in degree of LD and complications
  6. What % of DS live to 1 yr?
  7. What causes early death in DS?
    • Congenital heart disease
    • AVSD
  8. What % of DS live to 50?
  9. What are the 3 cytogenetic causes of Downs? And which is most common?
    • Non-dysjunction at meiosis- most common 94%
    • Translocation 5%
    • Mosaicism 1%
  10. What does non-dysjunction at meiosis mean?
    • The pair of chromosome 21s fails to separate so that one gamete has 2 chromosome 21s and one has none
    • Fertilisation of the gamete with 2 chr21s gives rise to a zygote with trisomy 21
  11. Do parental chromosomes need to be analysed for non dysjunction?
  12. What maternal factor does non-dysjunction relate to?
    • Age
    • After having one child with T21 due to non-dysjunction, what is the4 risk of recurrence of DS? For under 35, and over 35
    • 1 in 200 for <35yo
    • Same as others for >35yo
  13. What is translocation?
    • When extra chr21 is joined onto another chr – usually 14
    • Unbalanced Robertsonian translocation (due to combo of normal chr of one parent + balanced translocation of another parent)
    • 3 chr 21
    • But affected child still only has 46 chr
  14. Do parental chromosomes need to be analysed for translocation? Why?
    • Yes as one of the parents carries a balanced translocation in 25% of cases
    • This makes risk of recurrence of T21 higher
  15. What is a balanced translocation?
    • Have 45 chromosomes
    • One has 2 joined chromosomes
  16. What causes mosaicism?
    Non dysjunciton at MITOSIS (rather than meiosis)
  17. What is the phenotype of mosaicism like?
  18. What are the 2 main structural defects found more in Downs?
    • Cardiac in 50%
    • Duodenal atesia
    • What are the 2 GI problems found more in Downs?
    • Duodenal atresia
    • Hirschsprung’s disease
  19. What is the XR sign of duodenal atresia?
    Double bubble
  20. What are the face and head features of Downs?
    • Flat occiput
    • Small ears
    • Small mouth and protruding tongue
    • Upslanting palpebral fissures
    • Epicanthic folds
    • Flat nasal bridge
    • Brushfield spots in iris – pigmented spots
  21. What are the Mskel features of Downs?
    • Single palmar crease
    • Clinodactyly (little finger curves inwards towards others)
    • Sandal gap between toes
    • Hypotonia
    • Short neck
  22. What are the LATER medical complications of Downs – think in age terms?
    • Small stature
    • Delayed motor milestones
    • Learning difficulties
    • Hearing difficulties – recurrent secretory otitis media
    • Visual impairment – cataract, squint, MYOPIA
    • Acute leukaemia, solid tumours
    • Hypothyroidism
    • Coeliac disease
    • Epilepsy
    • Atlanto-Axial instability
    • Alzheimers
  23. what is the average IQ in Downs?
  24. What is Edwards syndrome?
    Trisomy 18
  25. Who does Edwards syndrome occur more in – female or male?
  26. What is the classic hand feature of Edwards syndrome?
    Overlapping fingers
  27. what is the main feature of achondroplasia?
    DISPROPORTIONATE short stature
  28. what are the 3 main features of achondroplasia?
    • short limbs
    • large head
    • abnormal neurology
  29. what are the complications of achondroplasia?
    • hydrocephalus
    • cervical cord compression
    • spinal stenosis
    • OSA
  30. what is the IQ of achondroplasia like?
  31. what is the inheritance of achondroplasia?
    auto dom
  32. which gene and chr is achondroplasia?
    • FGFR3 gene
    • chr 4
  33. what are the hands described as in achondroplasia?
  34. what is inheritance of marfans?
    auto dominant
  35. what are the skeletal features of marfans?
    • tall, thin
    • long limbs
    • arachnodactyly
    • pectus deformity
    • scoliosis
    • high arched palate
    • dural ectasia
  36. what are the 2 eye features of MARFANS?
    • upwards dislocation of lens
    • myopia
  37. what are 2 cardiac features of MARFANS?
    • aortic root dilatation
    • mitral valve prolapse
  38. what is the mutation of MARFANS? gene and chr
    • fibrillin 1 gene
    • chr 15
  39. what needs to be screened for in MARFANS?
    aortic root dilatation
  40. what does myotonia mean?
    delayed relaxation after sustained contraction
  41. what is the genetic problem in myotonic dystrophy?
    nucleotide triplet repeat expansion
  42. how will MD affect the generations?
    anticipation through generations
  43. how do newborns with MD present?
    • hypotonia
    • feeding difficulty
    • respiratory difficulty
    • due to muscle weakness
  44. how do you elicit myotonia in a person?
    • handshake
    • slow release
  45. how does MD present in older children?
    • myopathic facies - facial weakness
    • LD
    • myotonia
  46. what happens to adults in MD?
  47. what happens to men in MD?
    • baldness
    • testicular atrophy
  48. what is cause of death in MD?
  49. when the gene is maternally transmitted, what is the risk of?
    congenital myotonic dystrophy
  50. what is the most common autosomal recessive gene disorder?
    cystic fibrosis
  51. what are the respiratory symptoms or disorders of CF?
    • recurrent infections
    • bronchiectasis
    • thick secretions, mucus plugs
    • wheeze
    • progressive pulmonary damage - cor pulmonale
  52. what are the GI symptoms of CF?
    • meconium ileus, distal intestinal obstruction syndrome
    • pancreatic exocrine insufficiency (alter DM)
    • FTT
  53. what are the effects of CF on fertility?
    congenital absence of vas deferens
  54. what is the diagnostic test for CF?
    • sweat test
    • increased Na and Cl levels
  55. what is the gene mutation, on which chr in CF?
    • CFTR: cystic fibrosis transmembrane receptor
    • chr 7
  56. which delta mutation is in 75% of CF?
    delta F508
  57. what is the inheritance of PKU?
    auto recessive
  58. what is gene defect in PKU?
    • phenylalanine hydroxylase deficiency
    • so cant convert phenylalanine to tyrosine to melanin!
    • so have low tyrosine and low melanin
  59. how is the IQ in PKU affected?
    if treated within 30days of birth - get normal IQ
  60. what do most children with PKU look like?
    • fair haired blue eyed
    • hypopigmented as lack of tyrosine causes low melanin
  61. what neurological problem does PKU cause?
  62. what is Rx of PKU?
    dietary restriction of phenylalanine
  63. give egs of 2 x-linked recessive conditions affecting muscles?
    • DMD
    • BMD
  64. what is the mutation in DMD or BMD? whats the difference between the 2?
    • dystrophin gene mutation
    • DMD: none
    • BMD: some
  65. what is the wheelchair age of DMD and BMD?
    • DMD<12
    • BMD>12
  66. what is the IQ like in DMD and BMD?
    • DMD reduced in 50%
    • BMD normal
  67. what is the survival of DMD and BMD?
    • DMD 20-25y
    • BMD>30y variable
  68. what are the main features On examination of DMD?
    • proximal weakness
    • calf pseudohypertrophy
    • Gower maneouvre
    • contractures
  69. what is cause of death in DMD?
  70. what blood level is very high in DMD?
    very high CK
  71. what is the commonest cause of INHERITED mental retardation?
    fragile x
  72. what are the features of fragile x?
    • developmental delay
    • autistic
    • large forehead, long face, large prominent ears
    • macrocephaly
    • macro-orchidism
  73. what is the genetic problem in fragile x?
  74. can fragile x affect girls?
    if have the full expansion mutation then can have developmental delay or LD
  75. give 2 examples of x linked dominant disorders
    • x linked hypophosphataemic rickets
    • retts syndrome
  76. who do x linked dominant conditions affect?
    both carrier females and males
  77. how are mitochondria transmitted?
    • through ovum, not sperm
    • so males cannot transmit the disease
  78. which sex are affected in mitochondrial disease?
    • both
    • female may be symptomless carriers
  79. give examples of mitochondrial diseases?
    • Leber's Hereditary Optic Neuropathy
    • MELAS: mitochondrial encephalopathy with lactic acidosis and stroke like episodes
  80. what are the 2 types of chromosomal disorders?
    • numerical
    • structural
  81. what are the 3 autosomal trisomies found in live born infants?
    • downs T21
    • edwards T18
    • patau T13
  82. what are the 2 sex chromosome disorders?
    • Turners 45 XO
    • Klinefelters 47 XXY
  83. what are the 3 structural chromosome disorders caused by deletions?
    • prader-willi syndrome chr 15q deletion
    • cri-du-chat syndrome chr 5p deletion
    • wilms tumour with aniridia 11p deletion
  84. what are the dysmorphic features of turners?
    • short stature
    • webbed neck
    • widely spaced nipples
    • wide carrying angle of elbow
    • lymphoedema of hands and feet
  85. what are the structural defects in turners?
    • ovarian dysgenesis: streak ovaries - so amenorrhoea (kids via IVF donor egg)
    • cardiac: coarctation of aorta
    • renal anomalies
  86. why is oestrogen given in turners?
    • no proper ovaries
    • need oestrogen for development of 2ry sex char inc breasts
  87. when and why is progesterone given in turners?
    • towards end of puberty
    • uterine health
    • monthly withdrawal bleeds
  88. where is the lesion on cri du chat which chr?
  89. what are features of cri du chat syndrome?
    • cat like cry
    • round face
    • cleft palate
    • developmental delay
  90. what do you have to check the parents of cri-du-chat for?
    check parents for balanced translocation
  91. is it the maternal or paternal chr deletion causing prader-willi?
    paternal chr deletion

    • What are main features of prader-willi syndrome?
    • first FTT in infancy
    • then hyperphagia and obesity
    • learning difficulties
  92. is it the maternal or paternal chr deletion causing angelman syndrome?
    maternal chr deletion
  93. what are features of angelman syndrome?
    • happy puppet syndrome
    • ataxia
    • learning difficulties
    • happy disposition
  94. what kind of proteins do the mutated genes for autosomal dominant disorders encode for?
    structural protein
  95. what kind of protein is mutated in autosomal RECESSIVE?
    functional protein eg enzyme. as most carriers are not affected - they have sufficient enzyme levels to survive
  96. what is special about the transmission of x-linked disorders?
    • there is no male to male transmission
    • as fathers pass only their Y chr to sons
  97. what is an important x-linked disorder that affected the royal family?
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Genetic disorder.txt
2011-07-10 23:51:32

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