Genetic counseling


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Genetic counseling

  1. 1. Human Genetics By Dr Muhammad Saleem Laghari MBBS(KEMU), MCPS,FCPS (paeds) Gold Medalist FCPS-I Assistant Professor
  2. 2. GENETIC DISORDERS DEFINITION The genetic transmission of a particular disorder from parents to offsprings. FAMILIAL A condition occurring in certain families but not necessarily genetically transmitted
  3. 3. GENETIC COUNSELING Genetic counseling is the communication of information and advice about inherited conditions. A person giving genetic advice is called Counselor. A person seeking genetic advice is called consultand.
  4. 4. Stages in communication • History and pedigree construction. • Examination. • Diagnosis. • Counseling follow up.
  5. 5. Counseling steps • Accurate diagnosis is of paramount importance • Both parents should be counseled and adequate time allowed in an appropriate setting. • It is inappropriate to counsel too soon after the initial shock of serious diagnosis.
  6. 6. • Counseling needs to include all aspects of the condition, and the depth of explanation should match the educational background of the couple. • A geneticist must calculate the recurrence risk for the consultands; • risk of more than one in ten is considered high and of less than one in twenty low.
  7. 7. • Consultands often feel very guilty or stigmatized, and it is important to recognize and alley this. • Where there is an increased risk and specially where the disease is significant. The possibility of prenatal diagnosis for the condition needs to be considered if available. • This often encourages a couple to undertake a further pregnancy which otherwise they would be reluctant to risk. • Counseling must be non directive. The aim is to deliver a balanced version of the facts permitting parents to make their own decision.
  8. 8. Genetically transmitted diseases 1, CHROMOSOMAL DISORDERS Autosomal e.g, Trisomy 21 ,13 ,18 etc Sex chromosomes e.g, Turner Synd, Klinefelter Synd 2, SINGLE GENE DISORDERS Autosomal recessive Autosomal Dominant Sex –Linked recessive Sex Linked – Dominant 3, MULTIFACTORIAL inheritance
  9. 9. AUTOSOMOAL DOMINANT A a a a A a A a a a a a e.g, Achondroplasia, H. Spherocytosis
  10. 10. AUTOSOMAL RECESSIVE T t T t T T T t t T t t Thalassemia,Galactosemia
  11. 11. t t T t t T t t t T t t
  12. 12. X - LINKED DOMINANT X y x x X x X x y x y x
  13. 13. X x x y X x X y x x x y Vit D resistant rickets
  14. 14. X – LINKED RECESSIVE X Y X x X X X x YX Y x
  15. 15. MULTIFACTORIAL INHERITANCE • Combination of Genetic & Environmental factors. • General population incidence is 1% • For 2nd child 2—5% • For 3rd child 10 – 15 % • Risk for sibs & offspring is Equal
  16. 16. Prevention of genetic diseases There are several approaches for the avoidance of genetic disease, such as 1.Primary prevention 2.Population screening (prospective counseling). 3.Antenatal screening (prenatal diagnosis and selective termination) 4.Neonatal screening.
  17. 17. Primary prevention(Premarrital) • The populations in which a particular genetic disease is common and for which there is a simple diagnostic test for carriers. • School children or young adults can be screened and given appropriate advice about the choice of marriage partners e.g. thalassemia. Tay sachs disease.
  18. 18. Population screening • Programs are designed to identify conditions that occur frequently in HIGH RISK population • for example, screening of pregnant women to identify neural tube defects, screening for down syndrome in women over the age of 35.
  19. 19. Neonatal screening • Neonatal screening programs confined to conditions that are amenable to treatment and for which a reliable test exists like screening newborn infants • for congenital hypothyroidism and for phenyl ketonuria
  20. 20. Antenatal screening • It is possible now to identify certain serious hereditary diseases during the pre-natal period. A couple at risk of having a child with such a serious genetic disorder, may be screened and selective termination of pregnancy is done if the fetus is affected.
  21. 21. Current method of prenatal diagnosis First trimester Chorionic villous sampling Second trimester 1. Amniocentesis i) cells DNA Analysis. 2.Fetal blood sampling. 3. Biopsy of fetal skin and liver i) DNA Analysis 4. Ultrasound examination of fetus. 5. Fetoscopy. 6. Radiography.
  22. 22. Amniocentesis • Usually under taken at 15-16 week of gestation, 10-30 ml of amniotic fluid is withdrawn into a syringe under ultrasonographic guidance. • Fetal loss from amniocentesis is less than 0.5%. • Results can be provided within 14-21 days of the amniocentesis.
  23. 23. Amniotic fluid • Alpha feto protein level: (AFP) the level of this constituent of amniotic fluid increases between 14-18 week of gestation and falls steadily therefore. The level of AFP is raised in the following conditions: 1. Anencephaly 2. meningomyelocele. 3. Encephalocele4. omphalocele 5. Congenital nephrotic syndrome. 6. total abortion. 7. Intestinal atresia 8. Rh Isoimmunization
  24. 24. Cells in the amniotic fluids • Obtained by amniocentesis can be used for chromosomal analysis, biochemical assay, or DNA analysis. Two or three weeks are needed for the cells to multiply to a number adequate for testing.
  25. 25. Fetal blood sampling • Fetal blood sampling is being used for prenatal diagnosis at about 20 weeks of gestation for diseases like thalassemia, von willebrand,s disease, sickle cell anemia, red cell enzymes defect and disorder of white cell function such as chronic granulomatous disease. This procedure is associated with 2-5% fetal mortality and an increased maternal morbidity due to infection and hemorrhage.
  26. 26. Ultrasound • Ultrasound is used to determine gestational age, to rule out multiple pregnancies, to determine the sex of the fetus and to diagnose major congenital malformations. Fetoscopy Direct inspection of the fetus is possible but the risk to the fetus is about 5%. IT IS USED FOR OBTAINING SKIN BIOPSY.
  27. 27. Chronic villus sampling (CVS) • CVS is performed at 9-11 weeks of pregnancy, tissue is obtained by inserting a sampling device either trans-abdominal or trans-cervically under ultra sound guidance and tissue obtained. The fetal loss after CVS is about the same as for amniocentesis.
  28. 28. • The real advantage of CVS is early result. Each biopsy yields 10-15 mg of tissue which can be used for fetal sexing, total karyotyping, biochemical studies and DNA analysis. Fetal chromosome analysis is possible in 24 hrs as the cells need not to be cultured before analysis. DNA analysis and biochemical tests can be completed in 1-2 weeks.
  30. 30. • Background: In 1866, Down described clinical characteristics of the syndrome that now bears his name. • Down syndrome is by far the most common and best known chromosome disorder in humans. • Mental retardation, dysmorphic facial features, and other distinctive phenotypic traits characterize the syndrome • The cause of Down syndrome is full trisomy 21 in 95% of cases. Mosaicism (1%) and translocations (4%) account for the remainder of cases.
  31. 31. CLINICAL FEATURES • Skull: Brachycephaly, microcephaly, flat occiput, large fontanels with late closure, • Eyes: Up-slanting palpebral fissures, bilateral epicanthal folds, Brushfield spots (speckled iris), refractive errors (50%), strabismus (44%), nystagmus (20%), • Nose: Hypoplastic nasal bone and flat nasal bridge • Mouth and teeth: An open mouth with tongue protrusion, a fissured and furrowed tongue, tooth agenesis, malformed teeth, delayed tooth eruption, microdontia (35-50%)
  32. 32. • Ears: small with an over-folded helix. Chronic otitis media and hearing loss • Neck: Atlantoaxial instability (14%) can cause spinal cord compression. • Congenital heart defects: Congenital heart defects (40-50%); endocardial cushion defect (43%), ventricular septal defect (32%), secundum atrial septal defect (10%), • Gastrointestinal system (12%): Diastasis recti, umbilical hernia. Duodenal Artesia or stenosis, Hirsch sprung disease (less than 1%), TE fistula, Meckel diverticulum, imperforate anus,. • Genitourinary tract: Renal malformations, hypospadias, micropenis, and cryptorchidism occur.
  33. 33. • Skeleton: Short and broad hands, clinodactyly, increased space between the great toe and the second toe • Endocrine system: Hypothyroidism (16- 20%), diabetes, and decreased fertility. • Hematological system: 10- to 15-fold increased risk of developing leukemia. Neonatal Leukemoid reactions (ie, pseudo leukemia). Risk of hepatitis B carrier status is increased. • Immunodeficiency: 12-fold increased risk of developing infectious diseases, especially pneumonia, secondary to impaired cellular immunity. • Skin: Xerosis, localized hyperkeratosis lesions, alopecia areata (up to 10%), vitiligo, folliculitis, • Dermatoglyphics: Distal axial triradius in the palms, transverse palmar creases(simian crease).
  34. 34. • Premature aging: Decrease in skin & Muscle tone, early graying or loss of hair. • Growth: Short stature and obesity occurs during adolescence. • CNS: Moderate-to-severe mental retardation occurs, with an IQ range of 20- 70 (mean IQ is approximately 50). Hypotonia. Seizure disorder (5- 10%),senile dementia of Alzheimer type • Behavior: Genuine warmth, cheerful, gentleness, patience, an d tolerance are characteristics.
  35. 35.
  36. 36. INVESTIGATIONS • Clinical diagnosis should be confirmed with cytogenetic studies. • Karyotyping is essential for determination of recurrence risk. • In translocation Down syndrome, karyotyping of the parents and other relatives is required for proper genetic counseling. • Radiological investigations.
  37. 37. • BAER: Also known as brainstem auditory evoked response (BAER), Speech evaluation • Ophthalmic examination: Pediatric ophthalmic examination for vision screening and detection of ophthalmologic disorders. • Developmental chart: modified Denver Developmental Screening Test is available for assessing developmental milestones. • Growth charts
  38. 38. ANTENATAL SCREENING First trimester Chorionic villous sampling Second trimester 1. Amniocentesis i) fluids. ii) cells DNA Analysis. 2.Triple screen on Maternal blood 1) Alpha fetoprotein (Low) 2) Serum unconjugated oestriol (low) 3) HCG (High) 3. Quad screen. All above+ Inhibin level
  39. 39. • MORTALITY & MORBIDITY • Approximately 75% of concepti with trisomy 21 die in embryonic or fetal life. • Approximately 85% of infants survive to 1 year • 50% can be expected to live longer than 50 years. • The presence of congenital heart disease is the most significant factor that determines survival. • In addition, esophageal Artesia with or without transesophageal (TE) fistula, Hirsch sprung disease, duodenal Artesia, and leukemia contribute to mortality
  40. 40. Reproduction –Affected individuals rarely reproduce. –15-30% of females with trisomy 21 are fertile and they have a 50% risk of having an affected child. –Males are always INFERTILE.
  41. 41. Genetic counseling MATERNAL AGE In general 1 in 700 Mother age > 20 yr 1 in 2000 > 35 yr 1 in 50 > 40 yr 1 in 20
  42. 42. Genetic counseling Trisomy 21: –If the couple has a child with trisomy 21, the recurrence risk is about 1%. Translocation –Generally in translocation, the risk of Down syndrome in a subsequent pregnancy is estimated at 2-3%. –In a carrier parent with a 21q21q translocation or isochromosome, the recurrence risk is 100%.