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Prevalence is estimated at 1/20,000 live births. Male and female children are equally affected.

The clinical spectrum is broad and may include variable degrees of renal insufficiency, mild to severe life-threating neonatal respiratory distress/failure due to pulmonary hypoplasia, hyponatremia, hypertension and predisposition to urinary tract infections. Patients can progress to end-stage renal disease (ESRD) at varying ages. Congenital hepatic fibrosis (CHF) is invariably presents at birth, although may be clinically undetectable. The progressive manifestations of CHF typically include portal hypertension (pHTN), gastrointestinal varices and associated bleeding, bile duct disease (Caroli syndrome and cholangitis) and hepatosplenomegaly.

PKHD1 (6p12.2-3) is the most frequently identified causative gene, and encodes the ciliary protein fibrocystin. Mutations in a cilia-related gene, DZIP1L (3q22.3), encoding a zinc finger protein, has also been identified.

The hepatorenal phenotype and a family history consistent with autosomal-recessive inheritance is suggestive of the disease. Ultrasound typically shows hyperechogenic and enlarged kidneys, with retained contour and microcysts. Liver sonography shows biliary duct ectasia, a heterogeneous liver and possibly signs of pHTN and associated varices. Liver function tests typically remain in the normal ranges but thrombocytopenia and splenomegaly may be signs of pHTN. Genetic testing can confirm the causative mutation.

Main differential diagnoses are other hereditary cystic kidney diseases including autosomal dominant polycystic kidney disease, HNF1beta-associated cystic nephropathies, cystic kidney dysplasia and nephronophthisis, as well as rare metabolic diseases such as glutaric aciduria type II.

Suspicious prenatal ultrasound findings include bilaterally hyperechogenic, enlarged kidneys with poor cortico-medullary differentiation, with or without oligohydramnios and cysts. Prenatal genetic testing is possible where a mutation has been previously identified in a family member.

The pattern of inheritance is autosomal recessive. The risk of recurrence in siblings of an affected child is 25%.

Treatment is supportive with conservative management of chronic kidney disease and hepatic symptoms. In newborns, pulmonary hypoplasia may require mechanical or high frequency ventilation. Hypertension needs aggressive management, often requiring a combination of several drugs, among which angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) are the mainstays. Peritoneal dialysis is recommended as first choice renal replacement treatment (RRT) for children with end-stage renal disease (ESRD). Renal transplantation is the best solution in case of ESRD. Depending on the hepatic phenotype, combined liver and kidney transplantation may be necessary. Regular monitoring of the liver disease is required to identify complications. Liver transplantation may be necessary. Multidisciplinary support should be considered for associated neurocognitive and behavioral problems.

The disease is associated with reduced life expectancy, although survival is improving. In the case of neonatal respiratory distress, mortality has been described as high as 30-40%. For patients surviving the neonatal period, about 50% will develop ESRD within the first decade of life. CHF is an important cause of morbidity and mortality.