# Handbook of Genetic Counseling/Polycystic Kidney Disease

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, flattened 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.