© 2018, GENASSIST, Inc.     

By Keith S. Wexler, MBA, CFO, Business Development Director Life Sciences, GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

Polycystic Kidney Disease (PKD) is inherited in an autosomal dominant manner [ADPKD] – (50% risk to first degree relatives) or autosomal recessive manner [ARPKD] – (25% if both parents are gene carriers).

One of the characteristics of a disease caused by inheritance of a single deleterious gene (autosomal dominant inheritance) is variable severity.  This means that any or all children who inherit the deleterious gene (50% of children) could have milder or more severe problems related to their kidney function. 

  • Polycystic Kidney Disease has an incidence of approximately1:400 to 1:1000
  • Polycystic Kidney Disease  may be acquired

Autosomal Recessive Polycystic Kidney Disease (ARPKD) has an incidence of approximately 1 in 20,000. The condition is due to the inheritance of one disease causing (deleterious) mutation in the PKHD1 gene on the long arm of chromosome #6 (6p21.2-p12). 

Symptoms can vary from relatively mild very severe resulting in very low to no amniotic fluid in pregnancy resulting in respiratory insufficiency and pregnancy loss or early newborn demise.

When less severe, these children often experience significant kidney insufficiency often in the newborn period or the first several years of life resulting in early demise or kidney transplantation.

These infants often have cysts in the liver and may experience liver dysfunction, liver failure, bleeding abnormalities as well as feeding difficulties and recurrent infections.

Testing for most cases of autosomal dominant or autosomal recessive polycystic kidney disease is available through Invitae although Not all disease causing mutations have been identified.

Detection is estimated at approximately 80-90% for autosomal dominant disease and approximately 60% for detection of autosomal recessive disease.

Ciliopathies are a group of disorders which have many manifestations including:

  • Diabetes
  • Obesity
  • Eye abnormalities
  • Kidney disease
  • Abnormal bone development
  • Extra digits
  • Intellectual disability
  • Other neurological problems 

Most case of ADPKD (Autosomal Dominant Polycystic Kidney Disease) are due to one or more mutations in the PKD1 gene on the short arm on chromosome #16 (16p13.3) which is involved in the formation of the protein polycystin 1 (85% of cases) or the PKD2 gene on the long arm of chromosome #4 (4q21-13) which is involved in the formation or protein polycystin 2 (15% of cases).. 

If the mutation is identified in the patient then Preimplantation Genetic Diagnosis (diagnosis made on an embryo) becomes a possibility.

PKD causes multiple cysts to form in the kidneys, occasionally the liver and rarely the pancreas. Heart valve problems, abdominal wall hernias and intracerebral aneurysms can occur. 

The kidney cysts diminish kidney function eventually resulting in kidney failure.

The condition may be asymptomatic early in the course of the disease but can cause abdominal or back pain, blood in the urine, kidney stones, kidney infection, fatigue, joint pain and skin or nail abnormalities.

At least 400 mutations have been identified in the PKD1 gene [Polycystic Kidney Disease (Type I)] and over 40 mutations have been identified in the PKD2 gene.

Rarely, mutations in a third gene –PKD3 also can result in autosomal dominant PKD.

PKD can affect both the liver and kidneys and can result in serious renal problems either shortening the individual’s lifespan or resulting in kidney transplantation.