1. Pathophysiology Cases - Shruti

• Down syndrome - trisomy 21

  • 47, XY, +21
  • 47, XX, +21
• What is the most common cause of mental retardation?

  down syndrome
• Down syndrome - congenital heart defects?

  atrioventricular septal defect
• Down syndrome has increase risk of acute lymphoblastic leukemia
• Down syndrome - there is increase amyloid beta accumulation

  • high risk for developing early onset Alzheimer
• What is the most common gastrointestinal complication in down?

  duodenal atresia
• What can increase the risk of down syndrome?

  maternal age
• *** why does maternal age increase the risk of down syndrome?

  increase rate of nondisjunction in older ova

  • as a fetus - eggs are suspended in prophase I until ovulation
  • prior to fertilization - secondary oocyte are arrested in metaphase of meiosis II
• prenatal diagnosis with?

  amniocentesis or chorionic villus sampling
• Quadruple test during second trimester to test for serum level for down syndrome
• Quadruple test for down syndrome

  • decrease AFP
• Which inheritance of down syndrome give 46 chromosome?

  unbalance translocation
• non-disjunction causes aneuploidies

  • disjunction = normal separation of chromosomes to chromatids in anaphase 1 and 2 of meiosis
• when is nondisjunction more likely to occur?

  oogenesis during meiosis I
• Robertsonian translocation occur only in acrocentric chromosomes

  
• Robertsonian translocation - when does defect occur?

  • translocation carrier is not clinically affected
  • when carrier produce gametes leads to trisomy
• phenylketonuria - genetic defect in phenylalanine hydroxylase

  • infant unable to break down phenylalanine = builds up in blood causing intellectual disability
• Characteristic of classic phenylketonuria

  • elevated PKU
  • musty odor
  • deficiency in pigmentation = fair persion
• In phenylketonuria - excess phenylalanine can lead to?

  inhibition of tyrosinase = responsible for synthesis of melanin from tyrosine
• PKU - diagnosis

  • newborn screening of blood at 24-72 hour of age
  • if positive = put on semisynthetic formula low in phenylalanine
• Management of PKU

  • give tyrosine
• Deficiency of dihydrobiopterin reductase leads to hyperphenylalanemia

  • low dopamine levels
• decrease BH4 leads to lower dopamine = causing increase prolactin levels
• Maternal PKU syndrome - high level of PKU in moms is a teratogen in fetus
• Fragile X - clinical presentation

  • behavioral abnormality
  • hand flapping
  • autistic features
• Fragile X - CGG repeast in 5' UTR of FMR1 gene

  • result in hypermethylation
• Fragile X - anticipation = newer generation = worsen presentation + younger onset
• Osteogenesis imperfecta - autosomal dominant

  • brittle bones leading to decreased production of type 1 collagen
• Osteogenesis imperfecta is due to abnormal or absent alpha chain
• Clinical features of osteogenesis imperfecta

  • blue sclera
  • hearing loss
  • multiple fractures
  • dentinogenesis imperfecta
• type of osteogenesis imperfecta

  1. reduced synthesis of type 1 collagen
  2. structurally abnormal type 1 collagen
• Osteogenesis imperfecta - is affected by variable expressivity

  • same gene mutation with different phenotype
• Mitochondrial inheritance = mother to everyone
• LHON - leber hereditary optic neuropathy = passed by?

  mitochondrial mutation leading to optic neuropathy