L2

• Genetic disorders


  Disorders that can be passed from one generation to the next, result from some disorder in gene or chromosome structure
• Genes


  Basic units of heredity that determine both the physical and cognitive characteristics of people, composed of segments of DNA, woven into strands in the nucleus of all body cells to form chromosomes
• Phenotype


  The person's outward appearance or the expression of the genes
• Genotype


  The person's actual gene composition
• Genome


  Complete set of genes present, normal genome is 46XX or 46XY
• Mendelian inheritance


  • Discovered and described by Gregor Mendel in 1800's
  • A person who has two like genes for a trait is homozygous
  • If the genes differ, the person is heterozygous
• Dominant genes


  Dominant in action when paired with other genes, visibly expressed
• Recessive genes


  Genes that are not dominant, masked and do not show
• Homozygous dominant


  Individual with two homozygous genes for a dominant trait
• Homozygous recessive


  Individual with two genes for a recessive trait
• Aims of genetic counseling

  • Provide accurate information
  • Provide reassurance
  • Assist individual/couple to make informed choices
  • Educate individual/couple about the effects of genetic disorders
  • Offer support
• Who may benefit from genetic counselling

  • Couple with a child with a congenital disorder or inborn error of metabolism
  • Couple with close relatives who have a genetic disorder
  • Individual who is a known balanced translocation carrier
  • Individual with an inborn error of metabolism or chromosomal disorder
  • Consanguineous (closely related) couple
  • Woman older than 35 or man older than 45
  • Couples of ethnic backgrounds with specific illnesses
• Assessment for genetic disorders

  • Careful assessment of the pattern of inheritance
  • History
  • Physical assessment
  • Diagnostic testing

  
• Karyotyping


  Visual presentation of the chromosome pattern of an individual, specimen is venous blood/cells from buccal membrane, done at metaphase stage of mitosis, stained and photographed under microscope
• Maternal serum screening


  Tests for alpha fetoprotein-glycoprotein produced by the fetal liver, peaked in maternal serum between 13th and 32nd week, usually done at 15th week, elevated level indicates spinal cord disease, decreased level indicates trisomy 21
• Chorionic Villi Sampling


  Involves retrieval and analysis of chorionic villi, commonly done at 8-10 weeks, reveals genetic abnormalities like Retinoblastoma, myotonic dystrophy, sickle cell anemia, thalassemia
• Amniocentesis


  Withdrawal of amniotic fluid through the abdominal wall at 14th-16th week, needle is inserted and 20ml is aspirated
• Percutaneous Umbilical Blood Sampling


  Removal of blood from fetal umbilical cord at about 17 weeks using amniocentesis technique
• Legal and ethical aspects of genetic screening and counselling

  • Participation must be elective
  • Informed consent required
  • Results must be interpreted
  • Results must not be withheld, only given to those directly involved
  • No coercion for abortion or sterilization after counselling
• Trisomy 13 syndrome (Patau syndrome)


  • Extra chromosome 13, severely cognitively challenged, midline disorders like cleft lip/palate, heart disorders, abnormal genitalia, do not survive beyond early childhood
• Trisomy 18 syndrome (Edwards syndrome)


  • Three copies of chromosome 18, severely cognitively challenged, small for gestational age, low-set ears, small jaw, congenital heart defects, misshapen fingers/toes, rounded soles, do not survive beyond infancy
• Cri-du-chat syndrome


  • Missing portion of chromosome 5, abnormal cry, small head, wide-set eyes, downward slant to eyes, recessed mandible, severely cognitively challenged
• Turner syndrome


  • One functional chromosome, short stature, small & nonfunctional ovaries, webbed & short neck, wide neck folds, congenital anomalies like coarctation of aorta, kidney disorders, severely cognitively challenged
• Klinefelter syndrome


  • Males with an extra X chromosome, at puberty secondary sex characteristics do not develop, testes remain small & produce ineffective sperm, gynecomastia, high risk of male breast cancer
• Fragile X syndrome


  • Common cause of cognitive challenge in males, X-linked disorder with defective long arm of X chromosome, hyperactivity, aggression, autism, deficits in speech & arithmetic, large head, long face, prominent lower jaw, large protruding ears, obese, enlarged testicles after puberty, fertile & can reproduce, carrier females may show physical & cognitive characteristics
• Down syndrome (Trisomy 21)


  • Most common chromosomal disorder, high risk in women over 35, broad & flat nose, epicanthal fold, laterally upward slanting palpebral fissure, Brushfield spots in iris, protruding tongue, flat back of head, short neck, low set ears, poor muscle tone, short & thick fingers, Simian line on palm, IQ less than 20, congenital heart disease, prone to URTI & ALL, life span 50-60 years