Renal disease in Arima syndrome is nephronophthisis as in other Joubert‐related Cerebello–oculo–renal syndromes

Abstract

Clinicopathological features of the renal disease in Arima syndrome were studied in five autopsy cases. All cases showed insidious development of end-stage renal disease during childhood, preceded by polyuria/polydipsia, anemia, and growth failure. Decreased urinary concentrating ability and excessive sodium loss were the characteristic laboratory findings. Gross examination showed that both kidneys were small and showed multiple cysts of various sizes. The histological examinations revealed chronic sclerosing tubulo-interstitial nephropathy with cystic tubuli predominantly located at cortico-medullary areas. These observations suggest that the renal disease in Arima syndrome is in accordance with nephronophthisis both clinically and pathologically. Contrary to the previous literature which described that Arima syndrome can be distinguished from other Joubert-related cerebello-oculo-renal syndromes by its unique renal disease, i.e., cystic dysplastic kidney (CDK), our study indicates that the phenotype of the renal disease is common among these syndromes as well as abnormalities in other organs, suggesting the underlying similar molecular mechanisms.

Nephronophthisis-Associated Ciliopathies

“…This, together with the finding that BBS proteins localize to centrosomes, confirms the role of centrosomal proteins in cystic kidney diseases that are associated with diabetes, obesity, and retinitis pigmentosa (88,89). Additional NPHP-associated disorders are Sensenbrenner syndrome (cranioectodermal dysplasia) (90,91) and Arima syndrome (cerebro-oculo-hepato-renal syndrome) (92)(93)(94). NPHP has also been described in association with ulcerative colitis (95).…”

Joubert syndrome (and related disorders) (OMIM 213300)

“…Although these two renal lesions have been considered distinct, one report reviewed the renal pathology that had been described as cystic dysplasia in subjects with DekabanArima syndrome and found it to be indistinguishable from nephronophthisis. 27 Thus, it is possible that the renal manifestations in JSRD represent a continuum. The renal cystic disease recently described in some subjects with JS due to AHI1 mutations suggests that the onset of a nephronophthisis-like disorder may be delayed to as late as the third decade.…”

Nephronophthisis and Medullary Cystic Kidney Disease in Children

“…Children develop hepatomegaly and moderate portal fibrosis with mild bile duct proliferation. This pattern differs from congenital hepatic fibrosis, where biliary dysgenesis is prominent, and from hepatic involvement in ARPKD, Arima syndrome (cerebro-oculo-hepatorenal syndrome) [112][113][114], and Meckel syndrome, which exhibits bile duct proliferation. Bile duct involvement in these cystic kidney diseases may be explained by the ciliary theory, as the epithelial cells lining bile ducts (cholangiocytes) possess primary cilia.…”