Rare Combination of Phenotypes of Karyomegalic Interstitial Nephritis and Autosomal Recessive Polycystic Kidney Disease in an Omani Child.

Abstract

Autosomal recessive polycystic kidney disease is one of the most prevalent inherited cystic kidney diseases in infants and children, common in highly consanguineous societies such as Oman. Karyomegalic interstitial nephritis is a rare cause of hereditary chronic kidney disease presenting with progressive renal impairment and hematoproteinuria. We report a rare case of concurrent karyomegalic interstitial nephritis and autosomal recessive polycystic kidney disease in a two-year-old Omani boy. He presented with failure to thrive, developmental delay, hypotonia, recurrent urinary tract infection, proteinuria, and hematuria. Abdominal ultrasonography showed bilaterally enlarged kidneys with distorted parenchyma, loss of corticomedullary differentiation, and multiple small cysts in addition to an enlarged liver. Whole exome sequencing of the patient DNA revealed a homozygous likely-pathogenic variant in FAN1(NM_014967.4:c.2854C>T, p.R952*) segregating from each parent, in addition to a homozygous missense variantin polycystic kidney and hepatic disease 1(NM_138694.3:c.406A>G, p.T136A). Familial carrier testing in parents and a similarly affected brother revealed segregation of thepolycystic kidney and hepatic disease 1 variant in a homozygous state in the father and brother, and in a heterozygous state in the mother. This case demonstrates two rare genetic causes of chronic kidney disease within a highly consanguineous family, mimicking an autosomal dominant pattern of inheritance of cystic kidney disease. We recommend whole exome sequencing as a routine molecular diagnostic tool for children with cystic kidney disease, especially those from consanguineous families.