Any modality of renal replacement therapy can be a treatment option for Joubert syndrome

Yoko Takagi,Mariko Takei,Tomoo Yabuuchi,Naoto Kaneko,Takumi Takizawa,Chikage Yajima,Masataka Hisano,Motoshi Hattori,Kenichiro Miura,Kiyonobu Ishizuka,Yoshinori Tsurusaki,Yasuko Kobayashi,Yuka Ikeuchi,Naomichi Matsumoto

doi:10.1038/s41598-020-80712-4

Abstract

Joubert syndrome (JS) is an inherited ciliopathy characterized by a distinctive cerebellar and brain stem malformation which is known as the “molar tooth sign” on axial brain images, hypotonia, and developmental delay. Approximately 25–30% of patients with JS have kidney disease and many of them progress to end-stage kidney disease (ESKD). However, there are few reports on the outcomes of renal replacement therapy (RRT) in patients with JS and ESKD. In this study, we clarified the clinical features, treatment, and outcomes of patients with JS who underwent RRT. We retrospectively analyzed the medical records and clinical characteristics of 11 patients with JS who underwent RRT between June 1994 and July 2019. Data are shown as the median (range). Gene analysis was performed in 8 of the 11 cases, and CEP290 mutations were found in four patients, two had TMEM67 mutations, one had a RPGRIP1L mutation, and one patient showed no mutation with the panel exome analysis. Complications in other organs included hydrocephalus in two cases, retinal degeneration in eight cases, coloboma in one case, liver diseases in four cases, and polydactyly in one case. Peritoneal dialysis (PD) was introduced in seven cases, with a median treatment duration of 5.4 (3.4–10.7) years. Hemodialysis was performed using arteriovenous fistula in two cases, and kidney transplantation was performed 9 times in eight cases. Only one of the grafts failed during the observation period of 25.6 (8.2–134.2) months. The glomerular filtration rate at the final observation was 78.1 (41.4–107.7) mL/min/1.73 m2. The median age at the final observation was 13.4 (5.6–25.1) years, and all patients were alive except one who died of hepatic failure while on PD. Any type of RRT modality can be a treatment option for patients with JS and ESKD.

Highlights

Joubert syndrome (JS) is an inherited ciliopathy characterized by a distinctive cerebellar and brain stem malformation which is known as the “molar tooth sign” on axial brain images, hypotonia, and developmental delay
Joubert syndrome (JS) is a predominantly autosomal recessive ciliopathy characterized by a distinctive cerebellar and brain stem defect which is known as the molar tooth sign (MTS), hypotonia, and developmental delay[1]
CEP290, NPHP1, AHI1, OFD1, RPGRIP1L, CC2D2A, TMEM67, TMEM216, TMEM138, and TMEM237 have been reported to be associated with kidney d isease[1, 6, 14, 15]

Summary

Introduction

Joubert syndrome (JS) is an inherited ciliopathy characterized by a distinctive cerebellar and brain stem malformation which is known as the “molar tooth sign” on axial brain images, hypotonia, and developmental delay. There are few reports on the outcomes of renal replacement therapy (RRT) in patients with JS and ESKD. We clarified the clinical features, treatment, and outcomes of patients with JS who underwent RRT. The median age at the final observation was 13.4 (5.6–25.1) years, and all patients were alive except one who died of hepatic failure while on PD. JS was first reported in 1969 as a disorder based on neurological features, such as temporary hyperpnea, eye movement abnormalities, cognitive dysfunction, and cerebellar vermis hypoplasia[2]. There are few reports regarding renal replacement therapy (RRT) for JS patients who progressed to ESKD. We report the clinical features, treatment, and outcomes of 11 patients with JS who underwent RRT

Methods

Results

Conclusion