Diffuse renal cystic disease in children: morphologic and genetic correlations

Abstract

During a 5-year period, we evaluated seven infants and two fetuses who presented with enlarged, hyperechoic kidneys. In each, the initial clinical diagnosis was autosomal recessive polycystic kidney disease (ARPKD). Among the seven unrelated infants were three Caucasian and four African-American infants. No syndromic stigmata were evident in any of these infants. At the time of the initial evaluation, the family data were incomplete for four infants. The two fetuses were presumed to be at-risk for ARPKD based on the diagnosis in previous siblings. Renal histopathology was evaluated in all nine cases and revealed a spectrum of cystic disease ranging from ARPKD to glomerulocystic kidney disease to autosomal dominant polycystic kidney disease to diffuse cystic dysplasia. In the eight cases for whom liver histopathology was available, varying degrees of biliary dysgenesis were evident. We present a detailed analysis of the key histopathological features in each case and discuss the histopathological findings in an embryological context. In addition, we address the current role of molecular genetics in the diagnostic evaluation.

Anomalies of the TCF2 Gene Are the Main Cause of Fetal Bilateral Hyperechogenic Kidneys

“…Besides reporting for the first time the presence of a high prevalence of TCF2 gene anomalies in antenatal hyperechogenic kidneys, we confirm the typical in utero presentation of ARPKD with enlarged hyperechogenic kidneys Ͼ2 SD with loss of corticomedullary differentiation, presumably as a result of the numerous small cysts that are undetectable by ultrasound and the constant decrease in amniotic fluid volume (1,2,21). These characteristics resulted in TOP in 10 of 12 cases and one neonatal death in our cohort.…”

“…Moreover, pancreatic atrophy, urogenital abnormalities, abnormal liver enzyme levels, and hyperuricemia are observed in patients with TCF2 mutations (12)(13)(14)19,20). Prenatal forms also were described but only as a case report: Cystic renal dysplasia (8,9,12,16), bilateral hyperechogenic kidneys (14,21), renal agenesis, pelvicaliceal dilation, and multicystic dysplastic kidney (14). More recently, a pediatric phenotype related to TCF2 mutations had been reported in a large cohort (22).…”

Prenatal diagnosis of bilateral isolated fetal hyperechogenic kidneys. Is it possible to predict long term outcome?

“…Interstitial infiltration, sclerosis and multiple microscopic cortical and medullary cysts may account for hyperechogenicity even in the absence of macrocysts 1,9 . ARPKD, ADPKD and dysplasia are the most common causes for fetal renal hyperechogenicity.…”

Diagnosis and management of childhood polycystic kidney disease

“…In most clinical settings, the major distinction in the differential diagnosis of enlarged cystic kidneys in the pediatric patient is discriminating ARPKD from ADPKD. In fact, ADPKD presenting in the neonatal period may be clinically indistinguishable from ARPKD [8,9]. ARPKD (OMIM 263200) occurs less frequently (1:20,000 live births) than ADPKD, is generally diagnosed in utero or at birth, and occurs as a result of mutations in a single gene, Polycystic Kidney and Hepatic Disease 1 (PKHD1) [10][11][12].…”