Urologie pro praxi 4/2020

Polycystic kidneys in childhood – a wide range of overlapping diseases

Severe forms of early-onset polycystic kidneys in children represent a large group of diseases with overlapping clinical manifestations. A characteristic feature is enlarged kidneys with reduced function, which may be the result in Potter´s sequence in the prenatal period. However, the etiology of this manifestation is genetically very heterogeneous and can be caused by a disorder of a wide range of genes. The most common are PKHD1 mutations that lead to an autosomal recessive form of polycystic kidney (ARPKD). In almost the same number of cases the clinical manifestation of a severe form of polycystic kidney with onset in childhood is the result of PKD1 or PKD2 mutations associated with an autosomal dominant disease form (ADPKD). These mutations often arise de novo or can affect both alleles and lead to a recessive model of inheritance. Mutations in DZIP1L are a relatively new cause of the so-called ARPKD-like phenotype. Early and unambiguous diagnosis of these diseases will be confirmed by genetic testing. The current possibilities of next-generation sequencing allow simultaneous analysis of whole group of genes and represent a key role in the rapid diagnosis of these diseases. Causal gene identification is an essential tool for determining the correct diagnosis and parental counseling.

Keywords: ARPKD, PKHD1, DZIP1L, ADPKD, ciliopathies, HNF1β/TCF2, nephronophthisis.