Renal Dysplasia, Cystic, Susceptibility To

A number sign (#) is used with this entry because susceptibility to the development of cystic renal dysplasia (CYSRD) can be conferred by heterozygous mutation in the BICC1 gene (614295) on chromosome 10q21.

Clinical Features

Sase et al. (1996) described a family in which 3 sibs, a male and 2 females, were affected with nonsyndromic diffuse cystic dysplasia of the kidneys. The parents were nonconsanguineous and had no renal abnormality. A possibly similar condition was reported by Cole et al. (1976) in 3 sibs (2 females and 1 male) who were born to nonconsanguineous parents with apparently normal kidneys. The first affected sib died soon after birth; the other 2 were found to have the disorder by ultrasonography and the pregnancies were terminated. Autopsies were performed in all 3 cases. There were no other external or internal malformations except for hypoplastic lungs related to the renal abnormality. Sase et al. (1996) suggested that the disorder is an autosomal recessive. Diffuse cystic renal dysplasia is often seen in malformation syndromes, of which the investigators listed a number.

Kraus et al. (2012) reported 2 unrelated Caucasian boys with nonsyndromic cystic dysplasia. In the first boy, prenatal ultrasound at 22 weeks' gestation showed unilateral cystic dysplasia of the right kidney. After birth at age 38 weeks, sonography of the right kidney showed renal dysplasia with cysts, increased renal size, and hyperechogenicity. The left kidney was completely normal, and there were no other visceral abnormalities. Functional imaging showed hypofunction of the right kidney (34% of normal), but arterial hypertension was the only clinical manifestation. Last follow-up at 18 months of age showed normal psychomotor development, normal growth, and normal renal serum and urinary parameters. Both parents were asymptomatic, and there was no family history of a similar disorder. Prenatal ultrasound in the second boy showed a dysplastic left kidney and a hyperechogenic right kidney with normal size and shape. The boy was born at 32 weeks' gestation with normal renal function. Serial imaging showed that the right kidney became progressively normal, whereas the left kidney showed persistent abnormalities. He had a left low-grade vesicoureteral reflux and a nonfunctional left kidney, but no additional features. On last follow-up at age 5 years, the boy had normal growth and development. Family history was negative for renal failure and diabetes. Noting clinical overlap with the renal cyst and early-onset diabetes syndrome (RCAD; 137920), Kraus et al. (2012) could not exclude that these patients may later develop additional manifestations.

Molecular Genetics

In 2 (2%) of 92 children with isolated renal abnormalities who were negative for mutations in the HNF1B gene (189907), Kraus et al. (2012) identified 2 different heterozygous loss-of-function or hypomorphic mutations in the BICC1 gene (614295.0001 and 614295.0002, respectively). The authors examined the BICC1 gene because of a similar phenotype in murine knockout models. In each case, the mutation was inherited from an unaffected parent, suggesting that the disorder shows incomplete penetrance or that additional genetic or environmental factors are necessary for its development. No BICC1 mutation was found in 45 adults with kidney disease and early-onset diabetes.