Chromosomal Diseases

Diseases Resulting from Autosomal Chromosome Abnormalities

•  Down syndrome 
  • most common chromosomal disorder
  • most common cause of congenital mental retardation
  • causes
    • trisomy 21 
      • nondisjunction (most common cause) 
        • occurs during anaphase of meiosis I
      • Robertsonian translocation 
      • mosaicism (least common cause)
  • presentation  
    • appearance
      • short stature
      • hypotonia
      • unique facial structure
        • epicanthic folds, macroglossia, flat profile, depressed nasal bridge
    • simian crease in palm
  • ↑ risk for
    • congenital heart disease
      • combined ASD and VSD
    • AML (< 3 y/o)
    • ALL (> 3 y/o) 
    • Alzheimer’s disease
      • by 5th decade
      • due to amyloid precursor protein (APP) gene on 21
    • Hirschsprung’s disease, duodenal atresia, congenital heart anamolies
      • atrioventricular canal is most common
      • endocardial cushion defects also very common 
  • screening 
    • + quad screen  
      • ↓ α-fetoprotein
      • ↓ estriol
      • ↑ inhibin A
      • ↑ β-hCG
      • remember: high (hCG, inhibin); deficit (estriol, fetoprotein)
    • + ultrasound shows
      • high amount of fluid behind the neck
        • ↑ nuchal translucency
    • can confirm diagnosis with amniocentesis or chorionic villus sampling  
• Edwards’ syndrome 
  • most common trisomy resulting in live birth after Down syndrome
  • cause
    • trisomy 18  
      • nondisjunction
  • presentation
    • mental retardation
    • unique appearance 
      • rocker-bottom feet
      • micrognathia
        • small jaw
      • low-set ears
      • clenched hands with overlapping fingers
      • prominent occiput
    • congenital heart disease
      • VSD
  • death < 1 y/o
• Patau’s syndrome 
  • cause
    • trisomy 13 
      • nondisjunction
  • presentation
    • mental retardation
    • unique appearance
      • microphthalmia
      • microcephaly
      • cleft lip/palate
      • holoprosencephaly 
      • polydactyly
    • VSD
    • cystic kidneys
  • death < 1 y/o
• Cri-du-chat syndrome 
  • cause
    • microdeletion of short arm of chromosome 5 
  • presentation
    • high-pitched crying/mewing
      • origin of name: French for cry-of-the-cat
    • microcephaly
    • moderate to severe mental retardation
    • epicanthal folds
    • VSD
• Williams syndrome 
  • cause
    • microdeletion of long arm of chromosome 7
      • region lost includes elastin gene
  • presentation
    • distinctive “elfin” facies
    • mental retardation
    • hypercalcemia
      • ↑ sensitivity to Vitamin D
    • unique behaviors
      • well-developed verbal skills
      • extreme friendliness with strangers
      • musical talent
    • supravalvular aortic stenosis 
• 22q11 microdeletions  
  • cause
    • microdeletion at chromosome 22q11
      • abnormal embryological development of 3rd and 4th pharyngeal pouch
  • variable pressenation
    • CATCH-22 disease
    • cleft palate
    • abnormal facies
    • T-cell deficiency
      • due to thymic aplasia
    • cardiac abnormalities
    • hypocalcemia
      • due to parathyroid aplasia
      • results in tetany
  • specific presentation of 22q11 microdeletions
    • DiGeorge syndrome 
      • defects in
        • thymus
        • parathyroid
        • heart
    • velocardiofacial syndrome
      • defects in
        • palate
        • face
        • heart
• no abnormalities thymus, parathyroid