Unilateral or bilateral multicystic kidney disease is the most frequent renal abnormality found at prenatal ultrasound. The incidence of multicystic kidney disease is estimated between 1 on 1000 and 1 on 5000 births. As molecular testing became widely available, it is common to think at genetic causes first. Yet, multicystic kidney disease is mainly sporadic and with low recurrence risk in subsequent pregnancies. Usually cystic kidneys, which may be either reduced or enlarged, are caused by an obstruction at different levels during renal development. Multicystic kidneys can appear as isolated or as part of a complex malformation syndrome. In case an autosomal dominant form of the disease is suspected, renal ultrasound in the parents should be immediately performed. Indeed, in the absence of familiarity, autosomal dominant polycystic kidney is uncommon (about 95% of individuals with autosomal dominant polycystic kidney have an affected parent and about 5% have a de novo mutation). Autosomal dominant polycystic kidney disease can be caused by mutation in PKD1 or PDK2 (one additional locus representing a small fraction of families not linked to either the PKD1 or PKD2 locus is hypothesised but not proven). On the other side, autosomal recessive polycystic kidney disease (ARPKD, caused by PKHD1 mutations) is very rare (1 on 10,000/40,000). The parents of a patient affected with ARPKD are unaffected. A relatively forgotten form is renal cysts and diabetes syndrome, caused by heterozygous mutation in HNF1B (previously known as TCF2). HNF1B mutations can cause ecogenic kidneys and cystic dyplasia. The clinical manifestations associated with mutations in this gene are variable and can include abnormalities of the genital tract or maturity onset diabetes of the young. For additional information on TCF2, read also about 17q12 microdeletion syndrome.
FACTS
The PKD1 gene spans about 51.2 Kb and includes 46 exons. It is located on 16p13.3-p13.12.
The PKD2 gene spans about 74.1 Kb and includes 15 exons. It is located on 4q21-q23.
The PKHD1 gene spans about 476.3 Kb and includes 68 exons. It is located on 6p21.1-p12.
The HNF1B gene spans about 62.7 Kb and includes 9 exons. It is located on 17q12.
References:
DiMaio MS, Fox JE, Mahoney MJ, Prenatal diagnosis - cases and clinical challenges, Wiley-Blackwell, 2010.
Harris PC et al, Polycystic kidney disease, autosomal dominant (www.genereviews.org); last update: December 8, 2011.
OMIM 137920
