Handbook of Genetic Counseling/Abnormal Triple Screen and Family History of PKD

Abnormal Triple Screen and Family History of PKD

Introduction

• What have you been told about why you are here today?
• We want to discuss the triple screen results and what they really mean
• We want to get a family history to assess for any other risks related to pregnancy
• We want to talk about the different testing options available to you.

Family history update (at beginning depending on level of anxiety)

• Who in the family has been diagnosed with PKD?
• What age were they diagnosed?
• Do any of your family members have high blood pressure?
• Do any other people in your family have kidney problems?

Medical History (related to PKD)

• Do you see a doctor regularly?
• Are you currently on any medication?
• Have you had a renal ultrasound or CT scan?
• Have you experienced any urinary tract infections?
• Have you had high blood pressure?
• Have you experienced any pain in your stomach or back?

Pregnancy History

• Verify dates
• Any exposures?
• Any cig/alcohol/drug use?
• Any increase in blood pressure?
• Any ultrasounds so far? When is the next one scheduled?

Triple screen info.

• The test itself
  • Best results at 16-18 weeks gestation (can be done from 15-22 weeks)
  • Tests mother's blood
  • NOT diagnostic...simply an indication for additional testing
  • Uses three markers to determine indicators for certain fetal problems
• The three markers
  • produced by the fetus and the placenta
  • Alpha feto protein(AFP)
  • Human chorionic gonadotrophin (HcG)
    • Most sensitive risk factor for DS
    • Greater than 2.5 MOM indicated risk for DS
  • Estriol
    • Median of 0.5 MOM in Trisomy 18

Serum markers results

• AFP >2.5 MoM indicates a normal AFTN
• AFP <0.75 MoM indicates a Trisomy 21

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• hCG >2.5 MoM indicates a Trisomy 21
• hCG <0.55 MoM indicates a Trisomy 18

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• E3 <0.8 MoM indicates a Trisomy 18 or 21

Patient's results

• AFP =1.oo , HcG=2.21 , UE3=0.99
• Increased risk for Down syndrome

Explain chromosomes and what Down syndrome is

• Trisomy 21 (usually - every cell of body)
• Characteristics
  • mental retardation (mild to moderate)
  • heart difficulties
  • ear infections
  • Do everything a regular kid can…ride a bike, walk, talk
  • Slower to reach milestones
  • Facial features
• There is no cure

Calculating risk for Down Syndrome (explain how they determine num.)

• Look at maternal age + AFP MoM + hCG MoM + uE3 MoM = Down Syndrome Risk
• Risk ³ 1/270 is considered screen positive
  • This is equal to the midtrimester DSR for 35 year-old women
  • AMA woman's risk may be made less by the triple screen results, but it is still considered a test positive because of her age.

Recommendations for abnormal tests

• Ultrasound for examination of physical abnormalities
  • Down Syndrome
    • Nuchal fold (2nd trimester)
      • detects 34%
    • Nuchal translucency (1st trimester)
      • detects 77%
    • Short femur/humerus (detects 80-90% when combined with one of the following two)
    • Echogenic bowel
    • Short ear
• Amniocentesis
  • Explain procedure
  • 1/200 risk for complications
  • Can't detect all problems with the baby BUT will determine chromosome status
  • Fetal karyotype
    • Down Syndrome
    • Triploidy
    • Trisomies 13, 18
    • Other chromosomal abnormalities

The Basics of PKD

• Definition (Polycystic Kidney Disease)
  • Multiple cysts in the kidney leading to kidney dysfunction
• Prevalence = 1/400 - 1/1000
• Characteristics
  • 90% penetrant
  • initial signs = high blood pressure, blood in urine (50%), pain in side, back or abdomen, UTI, kidney stones (20-30%)
  • Final stage = renal failure (60%) after age 40
  • Mitral valve prolapse (26% compared to gen pop 2-3%)
  • aneurysms (5-10%) - occurs in familial clusters
  • liver cysts are possible
• Diagnosis/medical management
  • renal ultrasounds
    • only after age 30 is a negative ultrasound = 5% risk of disease
  • computed tomography (CT) - to detect aneurysm
  • MRI
• Prevention
  • Diet control = avoid red meat, eat low protein diet, less salt, fresh fruits and veggies, drink lots of water, avoid caffeine
• Treatment
  • For pain
    • acetaminophren may help
    • laparoscopic surgery to "unroof" cysts
  • For renal failure
    • dialysis
    • renal transplant (75-80% of kidneys work for 5 years)
• Inheritance (dominant more commonly - recessive is RARE)
  • Description of autosomal dominant and why this is the type
  • Chance of recurrence if the mother has it = 50% chance
  • Chance of recurrence if the mother doesn't have it same as population risk= <1%???? approximately 10% of the PKD patient community became infected through spontaneous mutation, and not through inheritance.
• Genetics
  • Two genes identified (a third suspected)
  • PKD1 - 16p (90% of PKD) DX is earlier, progresses more rapidly, more likely to be hypertensive
  • PKD2 - chromosome 4
  • Testing is done through linkage

Her options

• A amniocentesis for chromosome risk
• A renal ultrasound for herself (PKD surveillance)
  • If it is negative and she is 30+, chance of having PKD is <5%
• Testing by linkage analysis for herself and family
  • Costs approx. $2200 per family
  • >95% accurate in families
• Prenatal determination (preferably after linkage has been established)
  • CVS testing for linkage studies (9-15 weeks)
  • Amniocentesis for linkage studies (15+ weeks)

Psychosocial issues

• How her brothers illness has affected her
• Scared about the possibility of having PKD?
• Worried about PKD for baby?
• Would a diagnosis of PKD influence a pregnancy decision?
• How would having a child with DS feel?
• Support and resources at home?
• Would the dx of DS influence pregnancy planning?

Resources for patient

• [Polycystic kidney disease access center http://www.nhpress.com/pkd/]
• [www.adam.com http://www.adam.com]

Notes

The information in this outline has not been updated since 2003.