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
symptoms usually develop beginning in early adulthood although can be found in the infant period or not begin until later in adulthood
 * Etiology and Natural History
 * gene PKD1 mutated in about 85% of cases
 * gene PKD2 mutated in about 15% of cases
 * large amount of variability both within and between families
 * Prevelance 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
 * Prevelance and Inheritance
 * prevalence: 1/20,000 - 1/40,000
 * prevelance 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 chidren

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)