Polycystic Kidney Disease

Introduction

• Greet the family/parent
• What do you understand about why you are here in genetics today?
• What questions or concerns do you want to have addressed today?

Elicit Medical History

(interim history form)

• update medical history since last seen
• determine if there have been any problems since released from the hospital
• assess developmental history

Update Family History

• Update pedigree
• determine if there are any other family members with kidney problems, heart problems, liver problems or that died in early infancy

What is Polycystic Kidney Disease (PKD)?

• Two main types
  • Autosomal Dominant PKD (adult PKD)
  • Autosomal Recessive PKD (infantile PKD)

ADPKD

• Etiology and Natural History
  • gene PKD1 mutated in about 85% of cases
  • gene PKD2 mutated in about 15% of cases

symptoms usually develop beginning in early adulthood although can be found in the infant period or not begin until later in adulthood

• • large amount of variability both within and between families
• Prevalence and Inheritance
  • most common single gene disorder that is potentially lethal
  • prevalence at birth: 1/400 - 1/1000
  • 10% of cases due to new mutation
  • occurs in all races
  • inherited in autosomal dominant fashion
    • if one parent is affected there is a 50% chance of having an affected child
• Symptoms
  • multiple bilateral renal cysts (100% of cases)
    • leads to end stage renal insufficiency by 60 years old in 50% of cases
  • cysts in other organs specifically the liver (20% by 3rd decade; 75% by 6th decade)
  • intracranial aneurysms (10% of cases)
    • more common in patients with family history of intracranial aneurysms (22%) than those without this history (6%)
  • mitral valve prolapse and other heart defects
• Diagnosis
  • patients with known 50% risk
    • at least 2 cysts either unilateral or bilateral by 30years of age
    • large kidneys without cysts in infants and children
  • patients with no known risk
    • bilateral renal enlargements and cysts
    • in absence of indication for different renal cystic disease
    • suggestive of ADPKD, but not definite diagnosis
  • Differential from:
    • ARPKD - unaffected parents
    • Glomerulocystic kidney disease - minimal tubular involvement
• Molecular Testing
  • Linkage analysis - need a large number of family members to establish which gene is responsible
  • Prenatal Testing - only available after a mutation has been identified in an affected family member
• Management
  • no treatment for disease itself
  • treat symptoms to prevent premature death and alleviate pain

ARPKD

• Etiology and Natural History
  • mutation in PKHD1 locus (6p21) present in all studied patients with ARPKD
  • enlarged echogenic kidneys found in perinatal period
  • large amount of variability both within and between families
  • 30% of patients with ARPKD die in neonatal period
• Prevalence and Inheritance
  • prevalence: 1/20,000 - 1/40,000
  • prevalence may be underestimated due to death in neonatal period
  • carrier frequency: 1/70
  • inherited in autosomal recessive fashion
    • if both parents are carriers there is a 25% chance of having a child who is affected , 50% chance of having a child who is a carrier, and a 25% chance of having
• Symptoms
  • enlarged, echogenic kidneys with poor differentiation (100% of cases)
    • renal function impaired in 70-80% of cases
  • hypertension
    • usually occurs within first week of life
  • Liver disease (45% of cases at presentation)
  • pulmonary hypoplasia resulting from oligohydramnios
  • other abnormalities: low set ears, micrognathia, flattended nose, growth deficiency
• Diagnosis
  • enlarged echogenic kidneys with poor differentiation
  • one or more of the following:
    • absence of renal cysts in parents
    • signs of hepatic fibrosis
    • pathoanatomical proof of ARPKD in affected sibling
    • parental consanguinity suggesting AR inheritance
  • Differential from:
    • ADPKD - more likely to have bilateral macrocysts
    • Glomerulocystic kidney disease - minimal tubular involvement
• Molecular Testing
  • Linkage analysis - based on accurate diagnosis of ARPKD in affected individual and accurate understanding of relationships in family
  • Prenatal Testing - only available after a linkage has been identified in an affected family member
• Management
  • no treatment for disease itself
  • treat symptoms to prevent premature death and alleviate pain
    • stabilize respiratory function
  • feeding difficulty and growth failure in children

Psychosocial Issues

• uncertainty of diagnosis and prognosis may lead to anxiety
• possibity that parent could find out they have the diease (for ADPKD)
• guilt over passing trait to child
• Concern for risks to future pregnancies
• Are you interested in pursuing linkage analysis?
• How are you dealing with your son's health problems?
• Are you anxious about the possibility of upcoming surgeries?
• Reassure that this could not have been prevented

Recommended Follow-up for PKD

• renal ultrasounds to monitor cysts and function
• control of hypertension
• CT scan to detect aneurysm (ADPKD)
• monitor liver function

Resources

• PKD foundation (www.pkdcure.com)

References

• Practical Genetic Counseling
• OMIM
• GeneClinics
• GeneTests
• Human Congenital Malformations

Notes

The information in this outline was last updated in 2002.