exam 2

• Mitochondrial genes


  • Small amounts of DNA present in mitochondria
  • Inherited differently than genes on chromosomes; are not transmitted from parent to child like chromosomes
• Hereditary diseases resulting from mitochondrial DNA mutations

  Inherited differently from genetic mutations carried on chromosomes
• Trisomy 21 (Down's Syndrome)


  • Risk increases with maternal age
  • Caused from nondisjunction during meiosis
• Trisomy 21 (Down's Syndrome)


  • Manifestations: small square head, upward slant of eyes, small low-set ears, fat pad on back of the neck, open mouth with protruding tongue, simian crease, varying degrees of mental retardation, and behavioral issues
  • Also associated with congenital heart defects, ocular issues, leukemia, respiratory complications, gastrointestinal complications, hypothyroidism
  • 50% of patients develop Alzheimer's disease by age 50
• Diagnosis of Trisomy 21 (Down's Syndrome)


  Parental screening including amniocentesis, hormone levels, 4D ultrasound
• Treatment of Trisomy 21 (Down's Syndrome)


  Symptomatic and supportive
• Autosomal Dominant Disorders


  • Transmitted from an affected parent to offspring regardless of gender
  • 50% chance of transmission
  • Unaffected do not pass on the disorder
  • Delayed onset
• Autosomal Dominant Disorders


  • Marfan syndrome
  • Multiple neurofibromatosis
  • Achondroplasia
• Marfan Syndrome


  • Disorder of connective tissue
  • Mutation on chromosome 15 (FBN1)
  • Affects eyes, skeleton, and cardiovascular system
• Diagnosis of Marfan Syndrome


  History, physical examination, skin biopsy (presence of fibrillin), genetic testing
• Treatment of Marfan Syndrome

  • Surgical intervention for cardiac complications
  • Glasses/surgical intervention for vision correction
• Multiple Neurofibromatosis


  • Neurogenic tumors
  • Two forms: Type 1 (defect on chromosome 17 (NF1); subcutaneous lesions, café-au-lait spots, freckles, scoliosis, erosive bone defects, and nervous system tumors) and Type 2 (defect on chromosome 22 (NF2); tumors of the acoustic nerve)
• Treatment of Multiple Neurofibromatosis

  Palliative removal of tumors
• Autosomal Recessive Disorders


  • Rare
  • Both members of gene pair are affected
  • Affects both genders
  • Usually caused by a deficient enzyme
• Autosomal Recessive Disorders


  • PKU
  • Tay-Sachs
• PKU


  • Mutation on chromosome 12 (PAH gene) leads to an error in converting phenylalanine to tyrosine
  • Appears normal at birth then fails to meet milestones
  • Progressive neurological decline
  • If untreated, can lead to severe intellectual disability
• Diagnosis of PKU


  Serum phenylalanine at 3 days old
• Treatment of PKU


  • Avoid high protein foods
  • Pharmacologic interventions
  • Enzyme therapy
• Tay-Sachs


  • Progressive disorder due to mutation of hexosaminidase A
  • Necessary to metabolize certain lipids
  • Lipids accumulate, destroying and demyelinating nerve cells
  • Nerve cell destruction leads to a progressive mental and motor deterioration
  • Most are of Jewish decent
• Tay-Sachs


  • Appears normal at birth, then the infant begins to miss milestones
  • Progresses to seizures, muscular rigidity, and blindness
  • Usually fatal by 3-4 years of age
• Diagnosis of Tay-Sachs


  History, physical examination, and low serum and amniotic hexosaminidase A levels
• There is no cure for Tay-Sachs
• Sex-Linked Disorders


  • Almost always X linked
  • Males have a 50% chance of getting the disorder from their mother
  • Females have a 50% chance of being carriers
  • All daughters of affected males will be carriers, but none of their sons
• Sex-Linked Disorders


  • Fragile X syndrome
  • Turner Syndrome
  • Klinefelter syndrome
• Fragile X Syndrome


  • Associated with a single trinucleotide gene (FMR1) sequence on the X chromosome, which is repeated > 200 times
  • Plays a role in synapse development
  • Manifestations: long face with large mandible, large ears, large testicles, mental retardation, learning disabilities, speech delays, connective tissue disorders, behavioral issues, and autism spectrum disorder
• Diagnosis of Fragile X Syndrome


  History, physical examination, genetic testing
• Monosomy X (Turner's Syndrome)

  • Deletion of all or part of an X—occurs spontaneously
  • No Y chromosome, so female only
  • Manifestations: gonadal streaks instead of ovaries, short stature, neck webbing, small lower jaw, drooping eyelids, small fingernails, and widely spaced nipples
• Monosomy X (Turner's Syndrome)


  • Also associated with coarctation of the aorta, vision issues, hearing loss, renal and skeletal abnormalities, infertility, and increased risk for infections
  • No mental retardation present
• Diagnosis of Turner's Syndrome


  History, physical examination, chromosomal testing, and serum hormone levels
• Treatment of Turner's Syndrome

  Estrogen and growth hormones
• Trisomy X (Klinefelter's Syndrome)


  • One or more extra X chromosomes with the presence of the Y
  • Male appearance
  • Often undetected
  • Manifestations: gynecomastia, small testes and penis, tall stature, increased weight, and sparse body hair
  • Also associated with learning disabilities, behavioral problems, sexual dysfunction, pulmonary disease, varicose veins, osteoporosis, and breast cancer