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.