ARPKD and early manifestations of ADPKD: the original polycystic kidney disease and phenocopies.

Renal cysts are clinically and genetically heterogeneous conditions. Polycystic kidney disease (PKD) is common and its characterization has paved the way for the identification of a growing number of cilia-related disorders (ciliopathies) of which most show cystic kidneys. While the recessive form of PKD (ARPKD) virtually always presents in childhood, early onset can, in some instances, also occur in the dominant form (ADPKD). Both ADPKD genes (PKD1 and PKD2) can also be inherited in a recessive way, making the story more complex with evidence for a dosage-sensitive network. Several phenocopies are known, and mutations in HNF1ß or genes that typically cause other ciliopathies, such as nephronophthisis, Bardet-Biedl, Joubert syndrome and related disorders, can mimic PKD. An accurate genetic diagnosis is crucial for genetic counseling, prenatal diagnostics, and the clinical management of patients and their families. The increasing number of genes that have to be considered in patients with cystic kidney disease is challenging to address by conventional techniques and largely benefits from next-generation sequencing-based approaches. The parallel analysis of targeted genes considerably increases the detection rate, allows for better interpretation of identified variants, and avoids genetic misdiagnoses.

[Expression of epidermal growth factor receptor in renal biopsy from patients with adolescent nephronophthisis]. / Expresión del receptor del factor de crecimiento epidérmico en biopsias renales de pacientes con nefronoptisis del adolescente.

INTRODUCTION: In Venezuela has been described a new form of nephronophthisis, called adolescent nephronophthisis, with clinical and histological findings very similar to others varieties described. However, pathogenesis in not well known. The aim of this study was to determine the expression of human epidermal growth factor receptor (EGFR) in tubular epithelial cells of patients with adolescent nephronophthisis. METHODS: Renal biopsies of 8 patients with adolescent nephronophthisis were studied by immunohistochemistry to determine renal expression of EGFR. RESULTS: In all patients, there was no expression of epidermal growth factor receptor. CONCLUSION: These findings indicate a deficiency of growth factor receptor in undifferentiated epithelial cells, which could be one factor in the development of cysts in nephronophthisis.

The severe perinatal form of autosomal recessive polycystic kidney disease maps to chromosome 6p21.1-p12: implications for genetic counseling.

Autosomal recessive polycystic kidney disease (ARPKD) is a one of the most common hereditary renal cystic diseases in children. Its clinical spectrum is widely variable with most cases presenting in infancy. Most affected neonates die within the first few hours of life. At present, prenatal diagnosis relies on fetal sonography, which is often imprecise in detecting even the severe form of the disease. Recently, in a cohort of families with mostly milder ARPKD phenotypes, an ARPKD locus was mapped to a 13-cM region of chromosome 6p21-cen. To determine whether severe perinatal ARPKD also maps to chromosome 6p, we have analyzed the segregation of seven microsatellite markers from the ARPKD interval in 22 families with the severe phenotype. In the majority of the affected infants, ARPKD was documented by histopathology. Our data confirm linkage and refine the ARPKD region to a 3.8-cM interval, delimited by the markers D6S465/D6S427/D6S436/D6S272 and D6S466. Taken together, these results suggest that, despite the wide variability in clinical phenotypes, there is a single ARPKD gene. These linkage data and the absence of genetic heterogeneity in all families tested to date have important implications for DNA-based prenatal diagnoses as well as for the isolation of the ARPKD gene.

Quistes renales en el niño

Los quistes renales son dilataciones anormales de túbulos, conductos o glomérulos, o estructuras similares a divertículos posiblemente en continuidad con el nefrón. La enfermedad quística renal puede comprometer ambos riñones en forma difusa como en el riñón poliquístico o enfermedad autosómica dominante, o un área particular de ambos riñones como los riñones en esponja, o sólo un riñón o parte de él como en el riñón multiquístico. También hay un tumor quístico que puede reemplazar el parénquima renal normal como es el quiste multilocular. Finalmente el quiste simple puede ocurrir solo o junto a más quistes en cualquier lugar del riñón. La clasificación de los quistes con el propósito de simplificar conceptos no provee nacesariamente un marco práctico y clínico para tan diversos procesos patológicos. El advenimiento de la ecografía, la resonancia nuclear magnética y la tomografía computarizada ha mejorado drásticamente la habilidad del clínico para diagnosticar y diferenciar la variedad de enfermedad renal quística. Sin embargo, la importancia de una cuidadosa historia familiar es enfatizada por la clasificación de esa patología en categorías genéticas.